[Total hip arthroplasty combined with femoral head autograft for Crowe type II and type III developmental dysplasia of hip].
To evaluate the efficacy of total hip arthroplasty (THA) combined with femoral head autograft for Crowe type II and type III developmental dysplasia of the hip (DDH). From January 2001 to January 2004, THA was performed for 23 patients (29 hips) with osteoarthritis secondary to DDH. There were 20 females (26 hips) and 3 males (3 hips) with an average age of 52 years (range 43-65 years). Unilateral DDH occurred in 17 patients and bilateral DDH occurred in 6 patients. Based on radiographic classification of Crowe, there were 17 cases (20 hips) of type II and 6 cases (9 hips) of type III. The length difference was (2.9 +/- 0.8) cm between two lower limbs of the unilateral DDH patients. The Harris scores were 43.6 +/- 13.8 preoperatively. The standard procedure of THA was performed in 3 patients (4 hips), the structural femoral head autograft for restoring normal level of rotating center of the acetabulum in other patients. The incision healed by first intention in all patients. No patient suffered complications after operation. The duration of follow-up ranged from 4 to 7 years (average 5.6 years). The X-ray films showed bony healing between the grafted bone and the ilium in all patients. At last follow-up, the length difference was (0.9 +/- 0.2) cm between two lower limbs and the Harris score was 86.3 +/- 6.4; showing statistically differences (P < 0.05) when compared with preoperation. The X-ray films showed no dislocation of acetabulum, and femoral prosthesis, and no signs of dislocation, absorption and collapse of the grafted bone. THA combined with structural femoral head autograft for patients with osteoarthritis secondary to DDH can obtain favorable results. This method can restore normal level of rotating center of the acetabulum, provide reliable acetabular fixation, and restore acetabular bone stock in patients with Crowe type II and type III DDH.


Optogenetic dissection of basolateral amygdala projections during cue-induced reinstatement of cocaine seeking.
Stimuli previously associated with drugs of abuse can become triggers that elicit craving and lead to drug-seeking behavior. The basolateral amygdala (BLA) is a key neural structure involved in cue-induced reinstatement of cocaine seeking. Previous studies have also implicated projections from the BLA directly to the nucleus accumbens (NAc) in these behaviors. However, other structures critically involved in cocaine seeking are targets of BLA innervation, including the prelimbic prefrontal cortex (PL). It has been shown that BLA or PL innervation direct to the NAc can modulate reward-related behaviors but the BLA also projects to the PL, and given the importance of the PL projection to the NAc for reinstated drug seeking, we hypothesized the BLA to PL projection may indirectly influence behavior via PL innervation to the NAc. We delivered a virus expressing the inhibitory optogenetic construct ArchT into the BLA and implanted fiber optics above the injection site or axon terminal fields in either the NAc or PL. Rats then went through 12 days of cocaine self-administration followed by extinction training. Following extinction, animals underwent cue-induced reinstatement sessions in the presence or absence of optical inhibition. Inactivation of the BLA and either the BLA core subcompartment of the NAc (BLA-to-NAcore) BLA-to-PL projections inhibited cue-induced reinstatement. These data demonstrate that the BLA projection either directly into the NAc, or indirectly via the PL, is a necessary regulator of drug-seeking behavior.


Remote learning during COVID-19: cognitive appraisals and perceptions of english medium of instruction (EMI) students.
Many countries responded to the Covid-19 pandemic by transforming all face-to-face (F2F) courses to emergency remote teaching with a sudden decision. This rapid shift was unexpected and staggering for the university students. The purpose of the present study is to explore how students studying in English Medium Instructed (EMI) programs cognitively appraised the transformation from F2F to online learning, and to examine if there is any relation between perceived self-efficacy in academic second language (L2) use, quality of interaction, and course satisfaction. Using an online survey, data was collected from a total of 306 graduate and undergraduate students studying in different universities in Turkey. The study found that the majority of the students appraised the transformation as a threat. The students' cognitive appraisals and perceived level of interactional quality, and satisfaction negatively correlated. There was a strong positive correlation between the perceived level of interactional quality and satisfaction. Observed gender, major and year level differences are also reported. The findings have significant implications for decision makers and instructors. Universities are likely to continue remote teaching for a while, thus institutions need to capture how students are affected by the remote learning experience to envisage short and long-term scenarios, and to optimize the quality of their services accordingly.


Re-defining the characteristics of environmental volunteering: Creating a typology of community-scale green infrastructure.
One way to engage people with green infrastructure (GI) is as environmental volunteers. Previous studies explored the nature of such groups/projects in terms of the benefits they deliver such as their impact on levels of social capital within a pre-defined community. However, existing literature contributes little to our understanding of the composition, characteristics and mechanisms used to form and maintain these groups. As such, it is difficult to establish the influencing factors determining the capacity of a group to sustain its provision over time. This paper serves to offer a more nuanced understanding of local-scale environmental stewardship by outlining the diversity of volunteer-led GI activities observed at the community-scale. Evidence presented from a desk-based examination of observable activity within The Mersey area Forest in North-West England represents a re-conceptualisation of existing definitions of Community-Scale GI (CSGI). Using thematic criteria, the paper clusters characteristics into key classification affecting group dynamics, composition and objectives. Initial findings identified the following categories as being significant descriptors for community-scale green infrastructure: status, location, timeframe, membership, activity focus, governance, resources and recognition, and communications. Thus, we classify four distinct types of group engaged in voluntary activity contributing to local level GI creation and long-term management: 'Formal Group (Active), Formal Group (Inactive), Formal Project and Informal Group. Creating a nuanced typology of CSGI provides further opportunities to analysis the creation and long-term management of GI at a site, neighbourhood and city-scale. In turn, this contributes to our understanding of how multiple actors remain engaged in the decision-making processes of GI management and maintenance.


Model selection in measures of vascular parameters using dynamic contrast-enhanced MRI: experimental and clinical applications.
A review of the selection of models in dynamic contrast-enhanced MRI (DCE-MRI) is conducted, with emphasis on the balance between the bias and variance required to produce stable and accurate estimates of vascular parameters. The vascular parameters considered as a first-order model are the forward volume transfer constant K(trans) , the plasma volume fraction vp and the interstitial volume fraction ve . To illustrate the critical issues in model selection, a data-driven selection of models in an animal model of cerebral glioma is followed. Systematic errors and extended models are considered. Studies with nested and non-nested pharmacokinetic models are reviewed; models considering water exchange are considered.


Eye ontogeny in Pleurodema bufoninum: A comparison with Pleurodema somuncurense (Anura, Leptodactylidae).
Vision is one of the main sensory systems in amphibians, and the eye structure is highly associated with habitat conditions. The ontogeny, as well as the adult structure, of the eye has been studied in only a few species. The life change after metamorphosis is accompanied by changes in the visual environment. The aim of this work is to describe the eye ontogeny of Pleurodema bufoninum and to compare it with that of Pleurodema somuncurense. Specimens of both Pleurodema species were processed for histology analysis at different stages of development, including the tadpole, postmetamorphic, and adult forms. Eyes in both Pleurodema species are composed of the 3 tunics, tunica fibrosa, tunica vasculosa, and tunica interna, and the lens. Additionally, in both, the iris presents a projection on its dorsal and ventral free ends that screens the cornea. This structure has been reported in the eye of several anuran species and is called the umbraculum, meniscus or pupillary nodule. Our results show that the structures related to light capture (retina and lens) appear early in larval life, while the components of the terrestrial-life eye (scleral cartilage, specialized cornea, eyelids, nictitating membrane, and Harderian's gland) do not develop until the metamorphic climax, when the tadpole leaves the water. The adult eyes of P. bufoninum and P. somuncurense are very similar in structure and development.


Insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Asian patients with type 2 diabetes inadequately controlled on basal or pre-/self-mixed insulin: a 26-week, randomised, treat-to-target trial.
Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of IDeg and IAsp. This pan-Asian, 26-week trial investigated efficacy and safety of IDegAsp vs biphasic insulin aspart 30 (BIAsp 30) in Asian adults with type 2 diabetes (T2DM), inadequately controlled on once- or twice-daily (BID) basal, premixed or self-mixed insulin. Participants (mean age 59.8 years, HbA1c 8.4%, FPG 7.9 mmol/L, BMI 25.4 kg/m(2)) were randomised 2:1 to BID IDegAsp (n=282) or BIAsp 30 (n=142) and continued existing metformin treatment. Insulins were administered with breakfast and main evening meal, titrated to a pre-breakfast and pre-main evening meal self-measured plasma glucose target of 4-5 mmol/L. IDegAsp achieved the primary endpoint of non-inferiority to BIAsp 30 for mean change in HbA₁c (estimated treatment difference [ETD] IDegAsp-BIAsp 30: 0.05% points [95% CI -0.10; 0.20]). IDegAsp was superior in lowering fasting plasma glucose (FPG) (ETD -1.06 mmol/L, 95% CI -1.43; -0.70, p<0.001), and resulted in a lower final mean daily insulin dose (0.79 U/kg vs 0.99 U/kg, estimated rate ratio [RR] 0.79, 95% CI 0.73; 0.85, p<0.0001). Rates of overall confirmed and severe hypoglycaemia were similar between treatments, while rate of nocturnal confirmed hypoglycaemia was numerically (p=ns) lower with IDegAsp. During the maintenance period there was a trend (p=ns) towards lower hypoglycaemia rates for IDegAsp. In Asian adults with T2DM, IDegAsp BID effectively improves long-term glycaemic control, and compared to BIAsp 30, provides superior reductions in FPG with a lower dose, and numerically less nocturnal hypoglycaemia.


Psychoeducational Profile-Revised, Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Vineland Adaptive Behavior Scale, Second Edition: Comparison of Utility for Developmental Disabilities in Preschool Children.
This study aimed to compare the utility of the Psychoeducational Profile-Revised (PEP-R), Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (K-WPPSI-IV), and Vineland Adaptive Behavior Scale, Second Edition (VABS-II) for evaluating developmental disabilities (DD) in preschool children. Additionally, we examined the correlations between the PEP-R, KWPPSI- IV, and VABS-II. A total of 164 children aged 37-84 months were assessed. Children's development was evaluated using the PEP-R, K-WPPSIIV, VABS-II, Preschool Receptive-Expressive Language Scale, and Korean Childhood Autism Rating Scale, Second Edition. Of the 164 children, 103 had typical development (TD) and 61 had DD. The mean of the PEP-R Developmental Quotient (DQ), K-WPPSI-IV Full-Scale Intelligence Quotient (FSIQ), and VABS-II Adaptive Behavior Composite (ABC) scores were significantly higher in the TD group than in the DD group (p<0.001). The estimated area under the curve of the PEP-R DQ, K-WPPSI-IV FSIQ, and VABS-II ABC scores was 0.953 (95% confidence interval [CI]=0.915-0.992), 0.955 (95% CI=0.914-0.996), and 0.961 (95% CI=0.932- 0.991), respectively, which did not indicate a statistically significant difference. The PEP-R DQ scores were positively correlated with the K-WPPSI-IV FSIQ (r=0.90, p<0.001) and VABS-II ABC scores (r=0.84, p<0.001). A strong correlation was observed between the KWPPSI- IV FSIQ and VABS-II ABC scores (r=0.89, p<0.001). This study found that the PEP-R, K-WPPSI-IV, and VABS-II effectively distinguished DD from TD in preschool children, and no significant differences in utility were observed between them.


NADPH-diaphorase activity in the olfactory system of the hamster and rat.
A comparative analysis of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity in the olfactory bulb was conducted in the hamster and rat. The distribution and morphological features of NADPH-stained neurons were compared to those of glutamic acid decarboxylase-like (GAD-LI) and tyrosine hydroxylase-like (TH-LI) immunoreactive somata in order to relate NADPH-staining to neuronal classes with specific biochemical properties. Intense NADPH-staining was located in primary nerve fibers of the accessory and main olfactory systems, producing dense staining of individual glomeruli. The entire vomeronasal nerve and all glomeruli were stained in the accessory olfactory bulb, but olfactory nerve and glomerular staining were restricted to the dorsal half of the main olfactory bulb. The glomerular layer of the main olfactory bulb of both animals contained numerous small NADPH-stained neurons. The range of somal areas of these neurons was relatively narrow and averaged about 60 microns2 (ca. 8 x 11 microns). Most neurons possessed ovoid somata and monoglomerular intraglomerular dendrites. Previous Golgi studies indicate that such features characterize periglomerular cells. The somal areas of GAD-LI somata in the glomerular layer overlapped that of the NADPH-stained neurons, providing additional evidence that these neurons are probably periglomerular cells. The range of somal areas of TH-LI somata in the glomerular layer was broader and included both small and large neurons that usually possessed intraglomerular dendritic tufts. The smaller TH-LI somata corresponded in size to both the NADPH-stained and GAD-LI somata, suggesting an interrelationship among periglomerular cells, GAD-LI, TH-LI, and NADPH-diaphorase activity. The larger TH-LI somata were probably external tufted cells. In the external plexiform layer of the hamster, oriented NADPH-stained neurons were observed that possessed an intraglomerular dendrite. These neurons appeared to be middle tufted cells. Lightly stained and smaller neurons were occasionally seen in the mitral body and internal plexiform layers, corresponding in somal area and morphological features to those of type III granule cells. No internal tufted or mitral cells were stained. The largest NADPH-stained neurons were located in the inner half of the granule cell layer and were classified as Golgi cells. Their somata averaged 125 microns2 (ca. 10 x 17 microns). Many NADPH-stained neurons were observed in all subdivisions of the anterior olfactory nucleus, the anterior hippocampal rudiment, anterior and posterior levels of the piriform cortex, and the vertical and horizontal limbs of the diagonal band of Broca, all of which are known to provide centrifugal inputs to the olfactory bulb.(ABSTRACT TRUNCATED AT 400 WORDS)


[On precipitation in clinical dextran solutions (author's transl)].
Dextran precipitation has the same molecular weight distribution as the raw material. However, there are also high molecular shares of associates (aggregates). Precipitation which can be caused by change of temperature passes three stages: 1. Formation of dextran associated. 2. Growth of a dextran film (micro gel) 3. Exsiccation and precipitation.


[Prolapse of the urethra in black girls. Personal experience in 11 cases].
The author describes 11 cases of prolapse of the urethral meatus observed in black girls between January 1987 and July 1993 first in Gabon (n = 7) and subsequently in Niger (n = 4). All patients were under the age of 10 years. The revealing symptom was vulvar bleeding (n = 8) or blood in urine (n = 2). In the remaining case prolapse was discovered incidentally. In all cases diagnosis was achieved by physical examination revealing a soft mass that bled on contact. Treatment consisted in surgical resection which was always followed by an uneventful recovery. This experience confirms a predisposition to this uncommon disorder in black children in whom the incidence is probably underestimated. The clinical presentation is consistently the same and the mass can be mistaken for a malignant tumor or for injuries related to sexual abuse. The results of this study demonstrate that the treatment of choice for prolapse of the urethra is surgical resection which is simple, safe, and immediately and lastingly effective.


Comparison of calculated nasal resistance from Röhrer's equation with measured resistance at delta P150Pa.
Values of nasal resistance at delta P150Pa have been recommended by the International Standardization Committee for clinical use. However, this point seems somewhat high for quiet nasal breathing. To determine the usefulness of calculated nasal resistance at delta P150Pa from Röhrer's equation when transnasal pressure fails to reach the point, the values at delta P150Pa calculated from the method have been compared with actually measured nasal resistances at delta P150Pa by active anterior rhinomanometry with a nasal nozzle. The mean value of measured unilateral nasal resistance in 75 patients is 0.513 +/- 0.511 Pa/cm3/s on expiration and 0.335 +/- 0.193Pa/cm3/s on inspiration. The mean value of calculated nasal resistance from Röhrer's equation is 0.511 +/- 0.515Pa/cm3/s on expiration and 0.337 +/- 0.207Pa/cm3/s on inspiration. Correlations between measured and calculated nasal resistances have been assessed and are almost identical in both expiration and inspiration. Calculated nasal resistance at delta P150Pa from Röhrer's equation seems to be suitable for evaluation when transnasal pressure fails to attain the point.


Herpes simplex virus 2 modulates apoptosis and stimulates NF-kappaB nuclear translocation during infection in human epithelial HEp-2 cells.
Virus-mediated apoptosis is well documented in various systems, including herpes simplex virus 1 (HSV-1). HSV-2 is closely related to HSV-1 but its apoptotic potential during infection has not been extensively scrutinized. We report that (i) HEp-2 cells infected with HSV-2(G) triggered apoptosis, assessed by apoptotic cellular morphologies, oligosomal DNA laddering, chromatin condensation, and death factor processing when a translational inhibitor (CHX) was added at 3 hpi. Thus, HSV-2 induced apoptosis but was unable to prevent the process from killing cells. (ii) Results from a time course of CHX addition experiment indicated that infected cell protein produced between 3 and 5 hpi, termed the apoptosis prevention window, are required for blocking virus-induced apoptosis. This corresponds to the same prevention time frame as reported for HSV-1. (iii) Importantly, CHX addition prior to 3 hpi led to less apoptosis than that at 3 hpi. This suggests that proteins produced immediately upon infection are needed for efficient apoptosis induction by HSV-2. This finding is different from that observed previously with HSV-1. (iv) Infected cell factors produced during the HSV-2(G) prevention window inhibited apoptosis induced by external TNFalpha plus cycloheximide treatment. (v) NF-kappaB translocated to nuclei and its presence in nuclei correlated with apoptosis prevention during HSV-2(G) infection. (vi) Finally, clinical HSV-2 isolates induced and prevented apoptosis in HEp-2 cells in a manner similar to that of laboratory strains. Thus, while laboratory and clinical HSV-2 strains are capable of modulating apoptosis in human HEp-2 cells, the mechanism of HSV-2 induction of apoptosis differs from that of HSV-1.


Molecular and cellular basis of human olfaction.
The human olfactory systems recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants begins with the binding of an odorant ligand to a specific receptor protein in the ciliary membrane of olfactory neurons. To address the problem of olfactory perception at a molecular level, we have cloned, functionally expressed, and characterized some of the human olfactory receptors from chromosome 17. Our results show that a receptor protein is capable of recognizing the particular chemical substructure of an odor molecule and, therefore, is able to respond only to odorants that have a defined molecular structure. These findings represent the beginning of the molecular understanding of odorant recognition in humans. In the future, this knowledge could be used for the design of synthetic ideal receptors for specific odors (biosensors), or the perfect odor molecule for a given receptor.


[Research progress on alkaloid monomer analgesic preparations].
Pain is one of the problems that seriously affect people's quality of life for thousands of years. The causes of pain are complex and varied,and long-term pain can also lead to depression. It has become a research hotspot to develop analgesic preparations with significant drug effects and small side effects. Recent studies have shown that certain alkaloid monomers have analgesic targets such as γ-aminobutyric acid,cannabinoids,and capsaicin. If their preparation is applied to the analgesic field,they can make up for the defects such as strong addiction and side effects of traditional opioid and non-steroidal analgesic drugs,but there is no relevant literature to summarize the research results in this field. This article first introduces the mechanism of pain production and the target of analgesia. Based on this,the application status of alkaloid monomer analgesic preparations approved by China Food and Drug Administration( CFDA)( number varieties,type of dosage form,drug description,analgesic mechanism and advantages) was analyzed,and the research dynamics of alkaloid monomer analgesic preparations( new formulation and new technology) were reviewed. Finally,some problems in this field were pointed out,such as imperfect medication information,inadequate transformation of research results,and too few kinds of analgesic components in developed alkaloids. The development direction was also pointed out for the above problems,with a view to provide reference for further development and in-depth research.


Unusual bilateral traumatic maculopathy following whiplash injury.
An unusual extensive bilateral macular oedema (MO) with spontaneous resolution occurred following a car crash accident. Qualitative and quantitative analysis of the macular region using spectral domain optical coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) was performed daily during the first 7 days, as well as at 3 and 6 months following the accident. SD-OCT examination demonstrated extensive MO accompanied by neurosensory detachment and subretinal fluid. During the 7 days following the accident there was gradual resolution of the oedema accompanied by visual recovery. One year later no anatomical changes were observed, the mfERG showed complete recovery and visual acuity returned to normal level. Although whiplash is a common injury in motor vehicle accidents, whiplash maculopathy (WMP) is rarely reported, most likely due to underdiagnosis. Here we describe the spontaneous resolution of a severe MO after whiplash injury in a car crash accident.


Tumor induced osteomalacia.
We describe a case of mesenchymal tumor induced osteomalacia. Our patient presented a typical clinical and radiological picture of osteomalacia, with low serum phosphate. With the excision of the tumor, which was located in the right forearm, the serum phosphate concentrations increased to normal values within a week postoperatively and the symptoms improved dramatically.


Microchip UV absorbance detection applied to isoelectric focusing of proteins.
Isoelectric focusing (IEF) is considered as an attractive separation technique for biologically amphoteric compounds (e.g., proteins and peptides) based on their isoelectric point (pI). With the advancement in micromachining technology, microchip format IEF has attracted significant attention. Both single-point and whole column imaging detection (WCID) methods have been employed for analyzing the separation performance in a microchip. WCID is more favorable than single-point detection because the latter requires the focused bands to be mobilized and thus adds more complexity to the design and operation of such microchips. Fluorescence- and UV absorbance-based WCID have been successfully adapted in glass and PDMS microchips. We have developed polydimethylsiloxane (PDMS) microchips for IEF applications where UV-WCID is employed for evaluating the separation performance. The chips are designed for use in the iCE280 analyzer (Convergent Bioscience Inc., Toronto), for capillary-based IEF where UV-WCID is employed for analyzing the separation performance. Three kinds of microchips that have been successfully developed using standard soft lithography technology are described in detail.


A Retrospective Analysis of Denosumab for the Treatment of Bone Metastases in Chinese Patients With Breast Cancer.
Denosumab entered the Chinese market for the first time in 2020. Since it is a short period of time, there is a lack of data on its effectiveness and safety in Chinese people. The objective of this study was to evaluate the effectiveness and safety of denosumab in delaying skeletal-related events (SREs) in patients with breast cancer metastatic to bone. The study retrospectively analyzed data from breast cancer patients with bone metastases (BM) who were treated with denosumab in the First Affiliated Hospital of Nanjing Medical University from September 2020 to January 2022. The primary endpoint was SRE incidence at 1 year after receiving denosumab treatment. The secondary endpoints included time to first on-study SRE and safety. Descriptive analysis was utilized to display clinicopathological features. The Kaplan-Meier method was used to estimate the median time to first on-study SRE in total population and subgroups. Logistic regression analysis and χ2 test were employed to determine the potential factors influencing the occurrence of SREs. Fifty breast cancer patients with BM were enrolled in our study, and 54.0% of the patients had 5 or more metastatic bone lesions. After a median follow-up of 17.00 months, 24% of the patients developed SREs at 1 year after receiving denosumab treatment, and the median time to first on-study SREs was not reached. Five or more metastatic bone lesions were an independent risk factor for SRE occurrence (odds ratio = 6.06, 95% CI: 1.09-33.54, P = .039). The adverse events (AEs) associated with denosumab mainly included hypocalcemia (68.0%), periodontitis (28.0%), and myalgia (14.0%). Only 3 cases of grade III/IV AEs were reported, and no serious AEs occurred. Denosumab was effective and well tolerated in Chinese breast cancer patients with BM.


N-methyl pyrrolidone promotes ankle fracture healing by inhibiting inflammation via suppression of the mitogen-activated protein kinase signaling pathway.
N-methyl pyrrolidone (NMP), a small bioactive molecule, has the potential to stimulate bone formation and inhibit osteoclast differentiation. The aim of the present study was to investigate the effect of NMP on the inflammatory response and underlying molecular mechanisms in MG-63 cells. The mRNA and protein expression of cytokines from peripheral blood in children with or without ankle fracture were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA, respectively. MG-63 cells were pre-treated with/without NMP and stimulated with 1 µM bradykinin (BK). The production of cytokines from MG-63 cells was assessed by western blotting and RT-qPCR. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein were measured using western blotting and/or RT-qPCR. Western blotting was used to examine the activation level of mitogen activated protein kinase. Compared with healthy children, levels of tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-6 mRNA and protein were upregulated in children with ankle fracture. NMP treatment did not induce cytotoxicity in MG-63 cells. The BK-induced upregulation of TNF-α, IL-1β, IL-6, iNOS and COX-2 mRNA and protein was reversed in a dose-dependent manner by NMP. Furthermore, NMP downregulated the activation of c-Jun NH2-terminal kinase and p38 pathways, but not the extracellular signal-related kinase pathway. Therefore, the results of the current study demonstrate that NMP inhibits inflammation dependent on the mitogen-activated protein kinase pathway in MG-63 cells, indicating that it may be beneficial in the healing of fractures.


Antibiotic prophylaxis in elective colorectal surgery.
Antibiotics are often administered in elective colorectal surgery to prevent wound infection. The tendency for surgeons to prolong the administration of prophylactic antibiotic therapy in the postoperative period is a well-known fact. The aim of this study was to elucidate the pattern of prophylactic antibiotic utilization in elective colorectal surgery and to determine if evidence-based medicine is employed in relation to this practice. A cross-sectional study encompassing general surgeons performing elective colorectal surgery was performed. Questionnaires were distributed to 144 surgeons (national, academic and private health care). Questions pertaining to the type, timing and duration of antibiotic administration were asked. The prevalence of wound infection audit rate and whether or not there were specific guidelines related to antibiotic administration were also determined. The response rate obtained was 67% (n = 96). Although evidence from the current medical literature and recommended national guidelines support the use of single-dose prophylactic antibiotics, 72% of the respondents used more than a single dose. Forty surgeons (42%) claimed that their prescribing practice was supported by the medical literature, 31 respondents (32%) based their practice on hospital guidelines and personal preference was cited as a reason by 21 surgeons (22%). The remaining four respondents (4%) used a similar scheduling policy to that practiced by their colleagues in relation to antibiotic administration. There was no significant difference in antibiotic dose scheduling between national, private and university academic institutions (P = 0.85). These results suggest that a significant proportion of surgeons administer excessive and unnecessary doses of antibiotics in elective colorectal surgery. Further studies are required to uncover the reasons but lack of appropriate guidelines and failure to exercise evidence-based medicine are major factors that account for this practice.


Experience-dependent brain plasticity after stroke: effect of ibuprofen and poststroke delay.
Despite indications that brain plasticity may be enhanced after stroke, we have described impairment of experience-dependent plasticity in rat cerebral cortex neighboring the stroke-induced lesion. Photothrombotic stroke was centered behind the barrel cortex in one cerebral hemisphere of rats. Plasticity of cortical representation of one row of vibrissae was induced by sensory deprivation of all surrounding whiskers for 1 month, and visualized with [(14)C]-2-deoxyglucose autoradiography. In control rats deprivation resulted in an enlargement of functional cortical representation of the spared row of vibrissae. After a focal stroke neighbouring the barrel cortex, no plasticity of the spared row representation was found. Investigation of plastic changes with deprivation initiated 1 week and 1 month after stroke have shown that later poststroke onset of deprivation resulted in a partial recovery of cortical plasticity in the barrel field. Western blot analysis of proinflammatory enzyme cyclooxygenase-2 (COX-2) expression revealed its strong upregulation in the barrel cortex 24 h after stroke. When chronic treatment with the anti-inflammatory drug ibuprofen (10 mg/kg or 20 mg/kg) accompanied deprivation, plasticity was restored. Ibuprofen applied before the ischemia also prevented the poststroke upregulation of COX-2. The results strongly suggest that poststroke impairment of experience-dependent cortical plasticity is caused by stroke-induced inflammatory reactions that subside with poststroke delay and can be at least partially ameliorated by pharmacological treatment.


Sequence and structural difference favors a distinct preference of Wnt3a binding with co-receptor LRP6.
Wnt signaling pathway plays a key role in a wide array of development and physiological processes. Wnt proteins interact with two different co-receptors LRP5/6 and ROR 2, leading to different signal transductions in the cell. Though the Wnt family of proteins has high sequence similarity the specificity for particular co-receptor is not well understood. The choice of pathway is attributed to the binding of Wnt complex to the co-receptor. Our current study is a novel approach using homology modeling, docking, and structural alignment to unravel the structural differences between Wnt3a and Wnt5b binding to LRP6. The conservation of a protruding loop has been identified in Wnt3a protein indicating an enhanced ability of Wnt3a to bind to LRP5/6 against its counter parts. The docking studies have further substantiated the findings. This could potentially help us design and develop novel inhibitors targeting Wnt3a-LRP6 complex in specific tissues or disease states.


On the mechanical and electronic properties of thiolated gold nanocrystals.
We present a quantitative exploration, combining experiment and simulation, of the mechanical and electronic properties, as well as the modifications induced by an alkylthiolated coating, at the single nanoparticle (NP) level. We determined the response of the NPs to external pressure in a controlled manner using an atomic force microscope tip. We found a strong reduction in their Young's modulus, as compared to bulk gold, and a significant influence of strain on the electronic properties of the alkylthiolated NPs. Electron transport measurements of tiny molecular junctions (NP/alkylthiol/CAFM tip) show that the effective tunnelling barrier through the adsorbed monolayer strongly decreases by increasing the applied load, which translates in a remarkable and unprecedented increase in the tunnel current. These observations are successfully explained using simulations based on the finite element analysis (FEA) and first-principles calculations that permit one to consider the coupling between the mechanical response of the system and the electric dipole variations at the interface.


Mental models change rapidly with implicitly acquired information about the local environment: a two-tone image study.
The projection of 3-D objects to 2-D images necessitates a loss of information, thus the shape of volumetric objects depicted in images is inherently ambiguous. The results of 3 experiments suggest observers use mental models of the local visual environment to constrain image interpretation. These models change quickly and dramatically to accommodate implicitly acquired information. Observers viewed very high-contrast (2-tone) images of novel volumetric objects. Before priming, novel 2-tone images appeared 2-D. After incidental exposure to similar objects in grayscale or familiar objects in 2-tone, the test images appeared volumetric. Incidental leaming appears to alter observers' mental models, thus causing an alteration in image interpretation in the absence of any image change. Highlights were interpreted more accurately than shadows, suggesting shadows play a secondary role in shape recovery.


The effect of microwave on the interaction of flavour compounds with G-actin from grass carp (Catenopharyngodon idella).
In order to investigate the influence of non-thermal effects of microwaves on the flavour of fish and meat products, the G-actin of grass carp in ice baths was exposed to different microwave powers (0, 100, 300 or 500 W); the surface hydrophobicity, sulfhydryl contents, secondary structures and adsorption capacity of G-actin to ketones were determined. As microwave power increased from 0 to 300 W, the surface hydrophobicity, total and reactive sulfhydryls increased; α-helix, β-sheet and random coil fractions turned into β-turn fractions. As microwave power increased from 300 to 500 W, however, hydrophobicity and sulfhydryl contents decreased; β-turn and random coil fractions turned into α-helix and β-sheet fractions. The tendencies of adsorbed capacity of ketones were similar to hydrophobicity and sulfhydryl contents. The increased adsorbing of ketones could be attributed to the unfolding of secondary structures by revealing new binding sites, including thiol groups and hydrophobic binding sites. The decreased binding capacity was related to the refolding and aggregation of protein. The results suggested that microwave powers had obvious effects on the flavour retention and proteins structures in muscle foods. © 2017 Society of Chemical Industry.


Nepetin reduces virulence factors expression by targeting ClpP against MRSA-induced pneumonia infection.
The resistance of Staphylococcus aureus (S. aureus) to various antibiotics has increased dramatically due to the misuse of antibiotics, and thus the development of new anti-infective drugs with new targets is urgently needed to combat resistance. Caseinolytic peptidase P is a case in hydrolase that regulates the virulence level of S. aureus. Here, we found that nepetin, a small-molecule compound from traditional Chinese herbal flavonoids, effectively inhibits ClpP activity. Nepetin suppressed the virulence of S. aureus and effectively combated the lethal pneumonia caused by MRSA. The results of cellular thermal shift assay showed that nepetin could bind to ClpP and reduce the thermal stability of ClpP, and the KD value of 602 nM between them was determined using localized surface plasmon resonance. The binding mode of nepetin and ClpP was further investigated by molecular docking, and it was found that Ser-22 and Gln-47 of ClpP residues were found to be involved in the binding of nepetin to ClpP. In conclusion, we determined that nepetin is a ClpP inhibitor and an effective lead compound for the development of a virulence factor-based treatment for MRSA infection.


Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α.
Lysine (K)-specific demethylase 6B (KDM6B) is a histone H3K27 demethylase, which specifically catalyzes the demethylation of H3 lysine-27 tri/dimethylation (H3K27me3/2). KDM6B can activate gene transcription by promoting transcriptional elongation which is associated with RNA polymerase II and related elongation factors. So KDM6B is important for the regulation of gene expression. Previous studies have indicated that several histone demethylases such as KDM3A, KDM4B, and KDM4C are regulated by hypoxia-inducible factor (HIF). But, the effect of hypoxia on KDM6B is not fully understood. In this study, we found that the expression levels of KDM6B mRNA and protein are modestly up-regulated under hypoxia (1% O2) or mimic hypoxia (desferrioxamine mesylate or CoCl2 treatment) (P<0.05). The result of RNAi shows that the up-regulation of KDM6B is dependent on HIF-2α, but not on HIF-1α. The result of chromatin immunoprecipitation assay indicates that there is a hypoxia response element in KDM6B promoter (-4041 to -4037). The result of Co-IP assay indicates that KDM6B can form complex with HIF-2α or HIF-1α. The knockdown experiment implies that KDM6B is a potential regulator for HIF-2α target genes. These data demonstrate that KDM6B is a new hypoxia response gene regulated by HIF-2α. Our results also show that KDM6B is a potential co-activator of HIF-α, which is important for the activation of hypoxia response genes.


Pyranose dehydrogenase ligand promiscuity: a generalized approach to simulate monosaccharide solvation, binding, and product formation.
The flavoenzyme pyranose dehydrogenase (PDH) from the litter decomposing fungus Agaricus meleagris oxidizes many different carbohydrates occurring during lignin degradation. This promiscuous substrate specificity makes PDH a promising catalyst for bioelectrochemical applications. A generalized approach to simulate all 32 possible aldohexopyranoses in the course of one or a few molecular dynamics (MD) simulations is reported. Free energy calculations according to the one-step perturbation (OSP) method revealed the solvation free energies (ΔGsolv) of all 32 aldohexopyranoses in water, which have not yet been reported in the literature. The free energy difference between β- and α-anomers (ΔGβ-α) of all d-stereoisomers in water were compared to experimental values with a good agreement. Moreover, the free-energy differences (ΔG) of the 32 stereoisomers bound to PDH in two different poses were calculated from MD simulations. The relative binding free energies (ΔΔGbind) were calculated and, where available, compared to experimental values, approximated from Km values. The agreement was very good for one of the poses, in which the sugars are positioned in the active site for oxidation at C1 or C2. Distance analysis between hydrogens of the monosaccharide and the reactive N5-atom of the flavin adenine dinucleotide (FAD) revealed that oxidation is possible at HC1 or HC2 for pose A, and at HC3 or HC4 for pose B. Experimentally detected oxidation products could be rationalized for the majority of monosaccharides by combining ΔΔGbind and a reweighted distance analysis. Furthermore, several oxidation products were predicted for sugars that have not yet been tested experimentally, directing further analyses. This study rationalizes the relationship between binding free energies and substrate promiscuity in PDH, providing novel insights for its applicability in bioelectrochemistry. The results suggest that a similar approach could be applied to study promiscuity of other enzymes.


Development of Neutralizing Nanobodies to the Hemagglutinin Stem Domain of Influenza A Viruses.
The influenza virus infection claims ~650,000 lives annually. Taking into account the evolving resistance of the pathogen to antiviral drugs and the waning effectiveness of vaccination among certain populations, new approaches to the treatment of influenza are needed. The current study is aimed at obtaining single-domain antibodies (Nanobodies®) to the highly conserved stem domain of influenza A virus hemagglutinin by phage display. Two high-affinity neutralizing clones of Nanobodies® with a particular specificity were selected; they ensured 100% neutralization of the H1N1 and H5N2 influenza viruses in vivo. The obtained data demonstrate that it is possible to develop highly effective VHH-based drugs for the treatment of influenza.


Biomechanical evaluation of spring system for implant-supported prosthesis: analysis by photoelasticity and extensometry.
New systems are released in the odontological market with the objective of bringing improvements and advancements in the clinical success of implants and implant-supported prostheses. The distribution of tension for the bone/implant system of these new systems is important. The purpose of this work was to evaluate, by photoelastic analysis and strain gauges, the distribution of tension for the bone/implant system, using the Slim system. A photoelastic cast with an external hexagon implant was manufactured and a metal prosthesis was screwed below it, with or without the tested system. For the photoelasticity methodology, a photoelastic cast, with or without the tested system, was positioned in a circular polariscope, and axial loads of 100 N were applied to the centre of the crown. The pattern of tension generated was photographed and analysed qualitatively in an imaging programme. For the extensometry methodology, two extensometers were placed in the mesial and distal region of the implant in the photoelastic cast. The axial loads were applied to the group again, with or without the system (n = 10). The t test of independent samples with a significance level of 5% was used for this analysis. This study demonstrated greater tension values for both the photoelastic and extensometry methods when the tested system was used. Clinical studies must be performed to evaluate the tested system because the results might not be clinically significant to a bone reabsorption.


Reevaluating the green contribution to diatom genomes.
Photosynthetic diatom plastids have long been suggested to have originated by the secondary endosymbiosis of a red alga. However, recent phylogenomic studies report a high number of diatom nuclear genes phylogenetically related to green algal and green plant genes. These were interpreted as endosymbiotic gene transfers (EGT) from a cryptic green algal endosymbiosis. We reanalyzed this issue using a larger set of red algal genomic data. We show that previous studies suffer from a taxonomic sampling bias and point out that a majority of gene phylogenies are either poorly resolved or do not describe EGT events. We finally show that genes having a complete descent from cyanobacteria to diatoms through primary and secondary EGTs have been mostly transferred via a red alga. We conclude that, even if some diatom genes still support a putative green algal origin, these are not sufficient to argue for a cryptic green algal secondary endosymbiosis.


Early weight gain in family-based treatment predicts greater weight gain and remission at the end of treatment and remission at 12-month follow-up in adolescent anorexia nervosa.
To Identify whether early weight gain in family-based treatment (FBT) predicted greater weight and remission at end of FBT and 12-month follow-up. Eighty-two adolescents, with anorexia nervosa, participated in a randomized control trial comparing brief hospitalization for medical stabilization and hospitalization for weight restoration to 90% expected body weight (EBW) (1:1), followed by 20 sessions of FBT. Sixty-nine completed trial protocol. Receiver operating characteristic analyses were conducted investigating whether early weight-gain in FBT predicted outcomes at end of FBT and 12-month follow-up. Participants were analyzed according to their original randomization and as a combined set. Binary logistic regression was used to control for randomization arm effect in combined set analysis. Weight gain greater than 1.8 kg at FBT Session 4 predicted greater %EBW (99.18 SD = 6.93 vs. 92.79 SD = 7.74, p < .05) and remission at end of FBT (46% vs. 11%, p < .05) and at 12-month follow-up (64% vs. 36%, p = .05). Binary logistic regression confirmed weight gain greater than 1.8 kg predicted remission (p < .05) while treatment arm randomization did not add significantly to the model. Early weight gain has potential to distinguish likely responders in FBT from those who may need more intensive intervention to achieve remission offering the potential to improve outcomes.


Long-term clinical experience with laparoscopic ventral hernia repair using a ParietexTM composite mesh in severely obese and non-severe obese patients: a single center cohort study.
Background: The treatment of incisional and ventral hernias is associated with significant complications and recurrences, especially in severely obese patients. Recent studies have shown a reduced rate of surgical site infections and length of hospital stay in severely obese patients undergoing a laparoscopic ventral hernia repair.Aim: This study aims to describe the clinical experience in terms of efficacy and safety with laparoscopic ventral hernia repair using the ParietexTM Composite mesh (Covidien Sofradim Production, Trevoux, France) in severely obese patients (body mass index ≥35) compared with non-severe obese patients in a seven-year single-center cohort.Material and methods: All patients with a primary ventral or incisional hernia admitted to our hospital from 2006 until December 2012 who underwent a laparoscopic repair with the Parietex Composite mesh were included in this study. Pain scores using a numeric rating were collected prospectively 24-48 hours postoperatively. Patient data were retrospectively collected.Results: A total number of 210 patients were included; 173 with a BMI <35 and 37 with a BMI ≥35. Mean follow-up was 31 months. No statistically significant differences were found with regard to operation time, hospital stay, use of analgesics and postoperative complications. The long-term follow up recurrence rate in non-severely obese patients was 13% compared to 16% in severely obese patients (p = .60).Conclusion: Laparoscopic ventral and incisional hernia repair using the Parietex Composite mesh is feasible and safe in severely obese patients compared to non-severely obese patients.


Synthesis and Characterization of Site-Specific O6 -Alkylguanine DNA-Alkyl Transferase-Oligonucleotide Crosslinks.
O6 -Alkylguanine DNA-alkyltransferase (AGT), a DNA repair protein, can form crosslinks with DNA. The AGT-DNA crosslinks are known to be mutagenic when AGT is heterologously expressed in Escherichia coli, as well as in mammalian cells. To understand the biological consequences, reliable access to AGT-oligonucleotide crosslinks is needed. This article describes the synthesis and characterization of site-specific AGT-oligonucleotide crosslinks at the N2-position of deoxyguanosine and N6-position of deoxyadenosine. We developed a post-oligomerization strategy for the synthesis of propargyl-modified oligonucleotides. Copper-catalyzed azide-alkyne cycloaddition was used as a key step to obtain the iodoacetamide-linked oligonucleotides, which serve as good electrophiles for the crosslinking reaction with cysteine-145 of the active site of AGT. Trypsinization of AGT and hydrolysis of oligonucleotides, combined with analysis by liquid chromatography-tandem mass spectrometry, was utilized to confirm the nucleobase-adducted peptides. This method provides a useful strategy for the synthesis and characterization of site-specific DNA-protein crosslinks, which can be further used to understand proteolytic degradation-coupled DNA repair mechanisms. © 2019 by John Wiley & Sons, Inc.


Clinical nursing rounds part 2: nurse management rounds.
Clinical rounds are being introduced in the Dudley Group of Hospitals to improve patient care, involve patients and improve communication. There are four types of rounds: matrons' rounds, nurse management rounds, patient comfort rounds and teaching rounds. This article describes nurse management rounds, which involve the nurse in charge of the shift seeing each patient. This gives the nurse manager an overview of the condition and needs of all the patients on the wards and the ability of staff to meet these needs. These rounds have potential benefits for patients, relatives, for the nursing team and for other healthcare professionals.


Effects of Conservative Oxygen Therapy versus Conventional Oxygen Therapy on the Mortality in ICU Patients: A Meta-Analysis.
To compare the effects of conservative oxygen therapy and conventional oxygen therapy on the mortality of critically ill patients in ICU. Searching for randomized controlled clinical trials (RCT) on the effect of conservative oxygen therapy and conventional oxygen therapy on the mortality of critically ill patients in computer databases, including PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang, with postdate before August 2022. We have two researchers evaluating the quality of the literature included and extracting data as per the inclusion and exclusion criteria and then analyzed it with RevMan 5.4 statistical software. Primary outcome included short-term mortality (28-day mortality or ICU mortality); secondary outcome included 90-day mortality, ICU length of stay, hospital length of stay, incidence of new organ dysfunction in ICU, incidence of new infection in ICU, and incidence of ICUAW. A total of 5779 subjects were included in 10 articles, including 2886 in the conservative oxygen therapy group and 2893 in the conventional oxygen therapy group. The meta-analysis showed that conservative oxygen therapy had an advantage over conventional oxygen therapy in terms of short-term mortality (P=0.03). Subgroup analysis based on different conservative oxygen targets showed that this advantage was statistically significant when the target is set above 90% (RR = 0.76, 95% CI = 0.62∼0.94, P=0.01), while there was no significant difference between conservative oxygen therapy and conventional oxygen therapy when the target is set below 90% (RR = 0.95, 95% CI = 0.79∼1.16, P=0.63). In addition, in terms of the incidence of new infections in the ICU (P=0.03) and the incidence of ICUAW (P=0.03), conservative oxygen therapy also had advantages over conventional oxygen therapy, and the difference was statistically significant. But in terms of 90-day mortality (P=0.61), ICU length of stay (P=0.96), hospital length of stay (P=0.47), and incidence of new organ dysfunction in ICU (P=0.61), there was no significant difference between conservative oxygen therapy and conventional oxygen therapy. Compared with conventional oxygen therapy, conservative oxygen therapy can reduce the short-term mortality of severe patients, especially when the conservative oxygen therapy target is set above 90%. And it can also reduce the incidence of ICU new infections and ICUAW, while having no effect on 90-day mortality, ICU length of stay, and hospital length of stay.


Blood alcohol levels in suicide by hanging cases in the state of Sao Paulo, Brazil.
Suicide is one of the main causes of violent death worldwide, and has become a public health issue. Since alcohol consumption is associated with the increase in the number of suicides and hanging is one of the main methods used worldwide, the present study consists of an epidemiological analysis of BACs in victims of suicide by hanging autopsied in the State of Sao Paulo, Brazil. The objective of the present work was to establish an epidemiological profile and evaluate blood alcohol concentrations in victims of suicide by hanging in the State of São Paulo, Brazil, in the year of 2007. A cross-sectional retrospective study was conducted by collection of secondary data from autopsy reports of victims of hanging. According to the present study, positive results for alcohol were higher in male victims, but the mean BAC was higher in women.


Ionic conduction in Zn3(PO4)2.4H2O enables efficient discharge of the zinc anode in serum.
Batteries contain corrosive or reactive components necessitating containment in a case, setting a limit to their miniaturization. Miniature, small-capacity batteries could power medical sensors in the body, for example sensing glucose for diabetes management. A miniature, case-less Zn-Ag/AgCl battery would consist merely of a zinc anode and a bioinert gel-coated Ag/AgCl cathode, if both operated efficiently in the interstitial fluid. Such a battery has not previously been built, primarily because of rapid corrosion of Zn. We show that the corrosion of zinc is significantly reduced by growth of Zn2+-ion-conducting, O2-impermeable, hopeite [Zn3(PO4)2.4H2O] lamellae on the Nafion-coated Zn anode. The hopeite lamellae allow discharge of the Zn anodes over three weeks at 86% current efficiency in physiological buffer and at 60% efficiency over two weeks in serum. The Zn|physiological buffer|Ag/AgCl cell operates at 1.00 V at 13 muA cm-2 and at 0.94 V at 0.2 mA cm-2 anodic current density.


Method for DNA Ploidy Analysis Along with Immunophenotyping for Rare Populations in a Sample using FxCycle Violet.
The clinical use of flow cytometric DNA ploidy assay has been extended towards stratifying the risk of diseases, such as monoclonal gammopathies or B cell acute lymphoblastic leukemia, and to detect circulating tumor cells, both of which require detection of minute cell populations. This unit describes a protocol for determining DNA ploidy in fixed samples with simultaneous surface immunophenotyping. It is an easy method for simultaneous 6- to 8-color immunophenotyping and DNA content analysis using FxCycle Violet (FCV; DAPI) dye. This protocol is a one-step modification of routine multicolor immunophenotyping that includes surface staining followed by fixation and then DNA staining with FCV. It utilizes mature lymphocytes from the sample as an internal control for determination of DNA index. It is a sensitive method that allows DNA-ploidy determination and cell cycle analysis in a rare tumor population as low as 100 events, as well as DNA ploidy determination in various subsets of hematopoietic cells in the same sample based on their immunophenotype. © 2017 by John Wiley & Sons, Inc.


The ethnic density effect: results from a national community survey of England and Wales.
Using data from a community survey of 5196 ethnic minority and 2867 white respondents, together with data on local group concentration from the 1991 Census, the hypothesis was tested that ethnic group concentration is associated with lower levels of reported psychiatric symptoms. The hypothesis was broadly confirmed, both for within- and between-group differences. However, the effect was found to be modest in size and in one group, the Pakistani sample, was reversed. The findings are inconsistent with an explanation based on selection or drift. Linguistic factors contributed to, but did not explain the effects. Evidence on victimisation and mutual support suggests that social causation, in the form of reduced exposure to direct prejudice and increased social support, is a likely cause of the effect.


Bone scanning and photon absorptiometry in metabolic bone disease.
Bone scan imaging with the current bone-seeking radiopharmaceuticals, the technetium-99m labelled diphosphonates, provides a functional display of skeletal metabolism and has dramatically improved our ability to investigate skeletal pathology. While the role of bone scanning in metastatic disease was recognized early, and welcomed by oncologists and other specialists alike, in the field of metabolic bone disease the realization of its potential value has been slower, with perhaps more reluctant acceptance. Nevertheless, the skeleton remains an extremely difficult organ to investigate, and a familiarity with bone scanning should be an essential part of the investigational armamentarium for anyone with an interest in the metabolic bone disorders. The measurement of bone mineral by photon absorptiometry is a relatively new technique, which is rapidly gaining acceptance. The ability to accurately detect and quantify changes in bone mass is potentially of considerable value in the diagnosis and management of osteoporosis. The technique provides us with an extremely important and powerful research tool but, at the present time, its role in clinical practice has yet to be established.


Latency for facultative expression of male-typical courtship behaviour by female bluehead wrasses depends on social rank: the 'priming/gating' hypothesis.
Although socially controlled sex transformation in fishes is well established, the underlying mechanisms are not well understood. Particularly enigmatic is behavioural transformation, in which fish can rapidly switch from exhibiting female to male-typical courtship behaviours following removal of 'supermales'. Bluehead wrasses are a model system for investigating environmental control of sex determination, particularly the social control of sex transformation. Here, we show that the onset of this behavioural transformation was delayed in females that occupied low-ranking positions in the female dominance hierarchy. We also establish that expression of male-typical courtship behaviours in competent initial-phase (IP) females is facultative and gated by the presence of terminal-phase (TP) males. Dominant females displayed reliable TP male-typical courtship behaviours within approximately 2 days of the removal of a TP male; immediately following reintroduction of the TP male, however, females reverted back to female-typical behaviours. These results demonstrate a remarkable plasticity of sexual behaviour and support a 'priming/gating' hypothesis for the control of behavioural transformation in bluehead wrasses.


Bupropion sustained release: a therapeutic overview.
Sustained-release bupropion (bupropion SR) represents a new form of an already known effective antidepressant drug. Its pharmacokinetics, mechanism of action, metabolism, and efficacy are reviewed. Benefit relative to placebo has been demonstrated in two large multicenter trials, with low doses (100 or 150 mg) having been shown to have therapeutic efficacy. An overview of all placebo-controlled trials of bupropion SR is given, and the differential properties of bupropion and serotonergic drugs are described. The concept of a catecholamine-indolamine spectrum is presented, along with its implications for possible differential therapeutics of selective antidepressants.


MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.
Various diseases, including cancers, age-associated disorders, and acute liver failure, have been linked to the oncogene, MYC. Animal testing and clinical trials have shown that sustained tumor volume reduction can be achieved when MYC is inactivated, and different combinations of therapeutic agents including MYC inhibitors are currently being developed. In this review, we first provide a summary of the multiple biological functions of the MYC oncoprotein in cancer treatment, highlighting that the equilibrium points of the MYC/MAX, MIZ1/MYC/MAX, and MAD (MNT)/MAX complexes have further potential in cancer treatment that could be used to restrain MYC oncogene expression and its functions in tumorigenesis. We also discuss the multifunctional capacity of MYC in various cellular cancer processes, including its influences on immune response, metabolism, cell cycle, apoptosis, autophagy, pyroptosis, metastasis, angiogenesis, multidrug resistance, and intestinal flora. Moreover, we summarize the MYC therapy patent landscape and emphasize the potential of MYC as a druggable target, using herbal medicine modulators. Finally, we describe pending challenges and future perspectives in biomedical research, involving the development of therapeutic approaches to modulate MYC or its targeted genes. Patients with cancers driven by MYC signaling may benefit from therapies targeting these pathways, which could delay cancerous growth and recover antitumor immune responses.


Ambient exposure and nasal inflammation in adults and children--a preliminary analysis.
The epidemiological evidence that ambient exposure, including particulate matter (PM) is related to adverse health outcomes continues to mount. Inflammation and disease of the upper respiratory tract are commonly suggested as effects of ambient exposure. Therefore we studied both ambient exposure and nasal effects in a 4-months cross-sectional survey in Nordrhein-Westfalen (Germany). At 4 locations in 3 different cities ambient exposure to TSP (total suspended particles), O3, NOx and SO2 was derived from compliance measurements by governmental offices, and 884 subjects (501 mothers and 383 children, 6-7 years old) were screened using nasal lavage, with success rates of 90 and 75%, respectively. No differences in total cell counts or percentage of neutrophils were found between mothers or children from the 4 different locations, despite small but significant differences in ambient exposure to TSP, SO2, O3, and NOx during this period. A higher epithelial cell count in mothers and children from one city might be related to general higher ambient pollution in that location. Interestingly, total cells and interleukin-8 levels in children were higher than in mothers and possibly reflect their increased susceptibility to effects of air pollution. Future analysis will concentrate on temporal relations between inflammation and exposure, including individual risk factors such as allergy, smoking and the presence of disease.


Quality monitoring of care: ask the patient.
In 1998 and 1999, we organised a questionnaire to be filled out by chronic haemodialysis patients. The first part dealt with general information data on the specific patient and the second part dealt with quality assessment data given as experienced by the individual patient. This second part included a ranking of preference by the patients and aspects patients wanted to see improved in the future. As we implemented the EDTNA/ERCA Clinical Standards and Core Curriculum, the monitoring tool, as described in this paper, was developed in order to monitor the effect of implementation. As a result of this two-year monitoring process of quality of care, we can follow up the care provided by our multidisciplinary team. It has proven a very useful tool to find out what is to stay as it is and what is to be improved. Simply closing the loop!


[Acupuncture combined with oral western medication for Meniere's disease: a randomized controlled trial].
To compare the effect difference between acupuncture combined with western medication and simple western medication for Meniere's disease. Ninety-six patients with Meniere's disease were randomly assigned into a combination group (48 cases, 12 cases dropping) and a medication group (48 cases, 9 cases dropping). Betastatin mesylate tablets (once 12 mg, 3 times a day) and mecobalamin tablets (once 0.5 mg, 3 times a day) were prescribed orally in the two groups. Acupuncture was used in the combination group, twice a week, 20 min a time, and the acupoints were Baihui (GV 20), Fengchi (GB 20), Tinggong (SI 19), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), Fenglong (ST 40), Taichong (LR 3), Taixi (KI 3) and Tianshu (ST 25). All the treatment was given for continuous 12 weeks. The symptoms were observed by dizziness handicap inventory (DHI), tinnitus handicap inventory (THI), pure tone audiometry score and stuffy ear visual analogue scale (VAS). The effects were compared in the aspects of dizziness, hearing and activity. The scores of DHI, THI, pure tone audiometry and VAS scores after treatment were lower than those before treatment in the two groups (all P<0.05), with lower scores of the above 4 indexes in the combination group after treatment (all P<0.05). The difference values before and after treatment of the 4 indexes in the combination group were higher than those in the medication group (all P<0.05). The effective rates of dizziness, hearing and activity in the combination group were 97.2% (35/36), 91.7% (33/36), 88.9% (32/36), which were better than 71.8% (28/39), 74.4% (29/39) and 69.2% (27/39) in the medication group (all P<0.05). Acupuncture combined with conventional medication achieve better effect than simple conventional medication.


Single Cell Multiomics Identifies Cells and Genetic Networks Underlying Alveolar Capillary Dysplasia.
Rationale: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal developmental disorder of lung morphogenesis caused by insufficiency of FOXF1 (forkhead box F1) transcription factor function. The cellular and transcriptional mechanisms by which FOXF1 deficiency disrupts human lung formation are unknown. Objectives: To identify cell types, gene networks, and cell-cell interactions underlying the pathogenesis of ACDMPV. Methods: We used single-nucleus RNA and assay for transposase-accessible chromatin sequencing, immunofluorescence confocal microscopy, and RNA in situ hybridization to identify cell types and molecular networks influenced by FOXF1 in ACDMPV lungs. Measurements and Main Results: Pathogenic single-nucleotide variants and copy-number variant deletions involving the FOXF1 gene locus in all subjects with ACDMPV (n = 6) were accompanied by marked changes in lung structure, including deficient alveolar development and a paucity of pulmonary microvasculature. Single-nucleus RNA and assay for transposase-accessible chromatin sequencing identified alterations in cell number and gene expression in endothelial cells (ECs), pericytes, fibroblasts, and epithelial cells in ACDMPV lungs. Distinct cell-autonomous roles for FOXF1 in capillary ECs and pericytes were identified. Pathogenic variants involving the FOXF1 gene locus disrupt gene expression in EC progenitors, inhibiting the differentiation or survival of capillary 2 ECs and cell-cell interactions necessary for both pulmonary vasculogenesis and alveolar type 1 cell differentiation. Loss of the pulmonary microvasculature was associated with increased VEGFA (vascular endothelial growth factor A) signaling and marked expansion of systemic bronchial ECs expressing COL15A1 (collagen type XV α 1 chain). Conclusions: Distinct FOXF1 gene regulatory networks were identified in subsets of pulmonary endothelial and fibroblast progenitors, providing both cellular and molecular targets for the development of therapies for ACDMPV and other diffuse lung diseases of infancy.


[Drug resistance of Staphylococcus aureus in the field of obstetrics and gynecology].
Clinical isolates of bacteria from Department of Obstetrics and Gynecology were collected and their microbiological properties were investigated. The isolation frequencies of bacteria from this Department were almost similar to those from other hospitals, indicating the high isolation frequencies of gram-positive cocci. The drug resistance to various chemotherapeutic agents of Staphylococcus aureus including beta-lactam antibiotics was studied. It should be noted that the bacteria resistant to beta-lactam antibiotics were most often isolated and the resistance was due to the production of penicillinase. Methicillin-resistant strains of S. aureus were isolated from this Department at a high frequency. It was found that these strains are also resistant to many penicillins and cephems including methicillin. Methicillin resistance of these strains was found to be not due to the production of penicillinase. Examination of the penicillin-binding proteins (PBPs) revealed that a new PBP-2' was produced in a large amount, suggesting that the mechanism of methicillin-resistance was due to the production of the new PBP-2' as reported previously, not to the production of beta-lactamase. The increased isolation of methicillin-resistant strains may be due to the introduction and the overuse of beta-lactamase resistant antibiotics.


Should mediastinoscopy actually be incorporated into the FDG PET strategy for patients with non-small cell lung carcinoma?
Incorporating mediastinoscopy (MS) into the PET-based strategy for non-small cell lung carcinoma (NSCLC) patients might be cost-effective because MS can allow unnecessary thoracotomies to be avoided. The objective of our study was to assess the cost-effectiveness of incorporating MS into a PET strategy for NSCLC patients. To determine life expectancy (LE), quality adjusted life years (QALY), and the incremental cost-effectiveness ratio (ICER), a decision-tree sensitivity analysis was designed for histopathologically confirmed NSCLC patients with M0 disease, based on the three competing strategies of chest CT only vs. PET + CT vs. PET + CT + MS. A simulation of 1000 NSCLC patients was created using baselines of other relevant variables in regard to sensitivity, specificity, mortality, LE, utilities and cost from published data. One-way sensitivity analyses were performed to determine the influences of mediastinal metastasis prevalence on LE, QALY and ICER. The LE and QALY per patient in the CT only strategy, PET + CT strategy and PET + CT + MS strategy were 4.79 and 4.35, 5.33 and 4.93 and 5.68 and 5.33 years, respectively, with a 20% prevalence of mediastinal metastasis. The ICERs were 906.6 yen x 10(3) (7555 US dollars)/QALY/patient at a 20% mediastinal metastasis prevalence, and 2194 yen x 10(3) (18,282 US dollars)/QALY/patient at a 50% prevalence, but exceeded 5280 yen x 10(3) (44,000 US dollars)/QALY/ patient at 80%. Our study quantitatively showed the CT + PET + MS strategy in place of the PET + CT strategy in managing NSCLC patients to be cost-effective. MS should be incorporated into the PET + CT strategy for NSCLC patients except in those highly suspected of having mediastinal disease on chest CT or PET.


Molecular genetic testing in the management of pituitary disease.
Most pituitary tumours occur sporadically without a genetically identifiable germline abnormality, a small but increasing proportion present with a genetic defect that predisposes to pituitary tumour development, either isolated (e.g., aryl hydrocarbon receptor-interacting protein, AIP) or as part of a tumour-predisposing syndrome (e.g., multiple endocrine neoplasia (MEN) type 1, Carney complex, McCune-Albright syndrome or pituitary tumour and paraganglioma association). Genetic alterations in sporadic pituitary adenomas may include somatic mutations (e.g., GNAS, USP8). In this review, we take a practical approach: which genetic syndromes should be considered in case of different presentation, such as tumour type, family history, age of onset and additional clinical features of the patient. Review of the recent literature in the field of genetics of pituitary tumours. Genetic testing in the management of pituitary disease is recommended in a significant minority of the cases. Understanding the genetic basis of the disease helps to identify patients and at-risk family members, facilitates early diagnosis and therefore better long-term outcome and opens up new pathways leading to tumorigenesis. We provide a concise overview of the genetics of pituitary tumours and discuss the current challenges and implications of these genetic findings in clinical practice.


An efficient method for extraction of astaxanthin from green alga Haematococcus pluvialis.
Haematococcus pluvialis is one of the potent organisms for production of astaxanthin, a high value ketocarotenoid. Astaxanthin is accumulated in thick-walled cyst cells of Haematococcus. The thick cell wall is made up of sporopollenin-like material, algaenan, which hinders solvent extraction of astaxanthin. In the present study, an improved method for extraction of astaxanthin without homogenization of cells is reported. Extractability of astaxanthin from cyst cells was evaluated by treating cells with various solvents and pretreating the cells with organic and mineral acids at 70 degrees C followed by acetone extraction. Hydrochloric acid treatment facilitated 86-94% extractability of astaxanthin. Treatment time, temperature, and concentration of the acid were found to be critical factors for maximum extractability. The treatment did not affect the astaxanthin ester profile and the treated cells can be preserved until further use.


Personal recovery in the postdischarge period for individuals with schizophrenia spectrum diagnoses: The role of community integration and social support.
The experience of personal recovery from mental health has been theorized to occur through several pathways. CHIME is a seminal theoretical framework of personal recovery that is widely endorsed by the existing literature. Few studies have examined the utility of the CHIME framework with those experiencing acute challenges in their engagement in the recovery process. The purpose of the present study was to examine part of the CHIME framework for individuals with schizophrenia spectrum diagnoses in the period immediately following hospitalization. Specifically, the impact of social support and community integration on personal recovery was examined. The present study involved a secondary analysis of a Phase 2 clinical trial. Assessment measures were administered to participants 1-month (n = 82) and 6-months (n = 72) postdischarge from a psychiatric hospital. Hierarchical regression and mediation analyses were conducted to assess the relationship between social support, community integration, and 1-month and 6-month personal recovery. Hierarchical regression analysis indicated that community integration and social support significantly predicted personal recovery. Mediation analyses indicated social support partially accounts for the relationship between community integration and personal recovery at 1- and 6-months postdischarge, providing evidence for social support as a mechanism of personal recovery during this time. This quantitative investigation of CHIME highlights the mechanism of social support for individuals who are experiencing acute challenges in their recovery. These findings point to the need for interventions that enhance community integration and social support postdischarge. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Studies on the mechanism of action of LS 1727, a nitrosocarbamate of 19-nortestosterone.
LS 1727, a nitrosocarbamate of 19-nortestosterone, was active against lymphoid, antimetabolite-sensitive, cell lines in vitro especially L1210 and Ehrlich ascites tumour lines. It was less effective against alkylating agent-sensitive lines such as the Walker 256 carcinosarcoma. These results suggested a possible antimetabolite mode of action but LS 1727 had no effect on deoxy-or ribonucleotide pool sizes in L1210 cells. Studies on macromolecular synthesis showed an early inhibition of DNA synthesis whilst RNA and protein synthesis continued for 24-48 hours. This was reminiscent of a classic alkylating agent-like effect. In vivo studies with specific alkylating agent-sensitive, or antimetabolite-sensitive tumours showed no antitumour activity although significant inhibition of Ehrlich ascites tumour cell growth was observed at high doses. In vitro cytotoxicity studies showed LS 1727 to be inactivated in the presence of mouse, rat and dog liver supernatants. This would explain the poor antitumour effects in vivo compared with the in vitro observations. Because LS 1727 is a nitrosocarbamate its possible mutagenic activity was investigated. LS 1727 was highly mutagenic but this property was also lost in the presence of a rat liver microsomal fraction. Although an effective cytotoxic agent in vitro LS 1727 is only effective in vivo at toxic doses.


Engineered nanomaterial-mediated changes in the metabolism of terrestrial plants.
Engineered nanomaterials (ENMs) possess remarkable physicochemical characteristics suitable for different applications in medicine, pharmaceuticals, biotechnology, energy, cosmetics and electronics. Because of their ultrafine size and high surface reactivity, ENMs can enter plant cells and interact with intracellular structures and metabolic pathways which may produce toxicity or promote plant growth and development by diverse mechanisms. Depending on their type and concentration, ENMs can have positive or negative effects on photosynthesis, photochemical fluorescence and quantum yield as well as photosynthetic pigments status of the plants. Some studies have shown that ENMs can improve photosynthetic efficiency via increasing chlorophyll content and light absorption and also broadening the spectrum of captured light, suggesting that photosynthesis can be nano-engineered for harnessing more solar energy. Both up- and down-regulation of primary metabolites such as proteins and carbohydrates have been observed following exposure of plants to various ENMs. The potential capacity of ENMs for changing the rate of primary metabolites lies in their close relationship with activation and biosynthesis of the key enzymes. Several classes of secondary metabolites such as phenolics, flavonoids, and alkaloids have been shown to be induced (mostly accompanied by stress-related factors) in plants exposed to different ENMs, highlighting their great potential as elicitors to enhance both quantity and quality of biologically active secondary metabolites. Considering reports on both positive and negative effects of ENMs on plant metabolism, in-depth studies are warranted to figure out the most appropriate ENMs (type, size and optimal concentration) in order to achieve the desirable effect on specific metabolites in a given plant species. In this review, we summarize the studies performed on the impacts of ENMs on biosynthesis of plant primary and secondary metabolites and mention the research gaps that currently exist in this field.


Alterations in mental health and quality of life in patients with skin disorders: a narrative review.
The presence of lesions in visible areas of skin may cause emotional troubles in patients, including low self-worth, embarrassment, sorrow, and social isolation. Those alterations may predispose to psychiatric disorders such as anxiety, depression, and even suicidal ideation, severely affecting patients' health state and quality of life (QoL). In this article, we focus on dermatologic patients that present with secondary mental health alterations. Thus, we offer a detailed description of mental disorders observed in patients with acne vulgaris, atopic dermatitis, psoriasis, ichthyosis, vitiligo, and hidradenitis suppurativa. Moreover, we point out the relationship between the severity of the cutaneous symptoms with mental illnesses and QoL decline. Our objective was to highlight the importance of mental health care for patients with skin diseases. The impact of skin alterations on the mental health of dermatological patients should be a central concern. Likewise, the timely identification and treatment of mental disorders are essential for the comprehensive management of these skin diseases.


Influence of Glucose Dosage in Parenteral Nutrition on Body Thiamine Levels in Rats.
The objective of this study was to determine the relationship between glucose dosage in parenteral nutrition and reductions in levels of body thiamine in rats. Vitamin-free infusions with differing amounts of glucose were administered to normal or thiamine-deficient rats for 5 days, after which urinary thiamine excretion and the amounts of thiamine in the blood, liver, brain, and skeletal muscles were measured. The total energy dosage was set at three levels (98, 140, and 196 kcal/kg), and the dose of amino acids was constant among all groups. Urinary thiamine excretions on Day 5 decreased with increasing glucose dosage in the infusions. In normal rats, the amount of thiamine in the blood and all organs decreased compared with the diet group; however, no significant differences were found among the infusion groups. In thiamine-deficient rats, on the other hand, the amount of thiamine in the liver and skeletal muscles did not differ significantly among infusion groups; however, the amount of thiamine in the brain and blood decreased with increasing glucose dosage. An organ-specific correlation was found between glucose dosage in infusions and reductions in levels of thiamine. To prevent thiamine deficiencies from affecting the central nervous system, greater caution must be exercised during high-caloric parenteral nutrition. However, a constant supply of thiamine seemed to be essential, irrespective of the amount of energy supplied via parenteral nutrition, to maintain a sufficient level of thiamine in the body.


Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure-Activity Relationships and Membrane Targeting Properties.
Antibacterials that disrupt cell membrane function have the potential to eradicate "persister" organisms and delay the emergence of resistance. Here we report the antimycobacterial activities of 4-fluoro and 6-methoxyindoles bearing a cationic amphiphilic motif represented by a lipophilic n-octyl side chain at position 1 and a positively charged azepanyl or 1,4-dioxa-8-azaspiro[4.5]decane moiety at position 3. These analogues exhibited balanced profiles of potency (Mycobacterium bovis BCG, M tuberculosis H37Rv), selective activity, solubility, and metabolic stability. Bacteriological mechanism of action investigations on a representative analogue revealed cell membrane permeabilization and depolarization in M bovis BCG. These membrane-related changes preceded cell death indicating that the loss in membrane integrity was not an epiphenomenon. Bactericidal activity was observed against both growing and nongrowing mycobacterial cultures. The analogue also upregulated cell envelope stress-inducible promoters piniBAC and pclgR, implicating the involvement of envelope-related targets in its mode of action.


The Design and Validation of a Child Developmental e-Screening System.
An effective screening test could significantly impact identification of developmental delays at an early age. However, many studies have shown that delay screenings still use text-based screening survey questionnaires. Unfortunately, the traditional text-based screening method tends to be fairly passive. In addition, the advantages of using an interactive system and animation have been shown to lead to positive effects on learning in medical research. Therefore, a multimedia screening system is necessary. This study constructs a system architecture to develop an e-screening system for child developmental delays. To validate the system after development, this study conducted an experiment and employed a questionnaire to survey users. Five experts and 120 subjects participated in the experiment. After the experiment, the results of the system evaluation revealed excellent agreement between the text-based and multimedia version of Taipei II. A total of 118 (98%) participants preferred the multimedia version or had no preference, and only 2 (2%) preferred the paper version. Regular text-based screening sometimes excludes those with low literacy and those whose native language is different from the text. In addition, text-based screening tools lose users' attention easily. The current study successfully developed a multimedia text-based screening system. Feedback from the participants showed that the e-screening system was well accepted and more easily accessible than the original. In this study, a child developmental delays e-screening system was developed. After the experiment, the subjects indicated that the developmental delay e-screening system increased their comprehension and kept them interested in the screening.


[Phenotypic and functional analysis of T lymphocytes in cancer patients].
In preclinical tumor model and in human cancer, tumor antigen specific T lymphocytes play a key role in the control of tumor development. Nevertheless in numerous cases, the infiltrating tumor T cells do not seem to influence the clinical progression of the tumor. A better phenotypic and functional characterization of T cells in close contact with tumor associated with a comprehensive analysis of tumor evasion mechanism to the host response should lead to an optimization of cancer immunotherapy protocols.


Probabilistic model of decompression sickness based on stochastic models of bubbling in tissues.
Decompression sickness (DCS) is caused by gas bubbles formed from pre-existing and new microscopic gas nuclei in blood and tissues. Assuming a random pattern of bubbling processes in living tissues, we developed a probabilistic model of DCS. We hypothesized that symptoms of DCS in an individual exposed to decompression appear when the total volume of bubbles in a unit volume of any tissue, w(t), exceeds the critical specific volume of a free gas phase, wcr. Therefore, one may consider the expectation of w(t)/wcr as a measure of the dynamic risk of gas bubble lesion of a given tissue segment. Using the standard approach to estimation of various risks and the sum rule of probabilities of joint events, we defined the cumulative probability of DCS onset by the equation Pcum(t) = 1 - exp[Fcum(t)], where Fcum(t) = sigmaVnQnMnc(t), Qn = 1/wncr, where Vn is the volume of a tissue n. The function Mnc(t) coincides with the function Mn(t), defining a time history of the expectation of wn(t) until it achieves its maximum and then becomes a constant. Evaluating Pcum(t) for particular altitude decompressions, we identified the additive cumulative risk function of development of any DCS symptoms, Fcum-tot(t), with the function defining the cumulative risk of any bubble lesion of the "worst" virtual tissue (WVT) of Type A. On the other hand, we identified the additive cumulative risk function of development of intolerable DCS symptoms, Fcum-int(t), with the function defining the cumulative risk of acute bubble lesion of the WVT of Type phi. We found parameters of the curves Pcum-tot(t) and Pcum-int(t) that fit the known empirical curves for the cumulative probability of DCS onset. For men performing mild exercise at 30 kPa after preoxygenation, our estimated parameters for curves Pcum-tot(t) indicate that the WVTs of Type A have nitrogen washout half-times of 260 and 290 min for preoxygenation times of 75 and 135 min, respectively. On the other hand, the parameters of curves Pcum-int(t) show that the WVTs of Type phi in men performing mild exercise at 20-40 kPa after preoxygenation during 0-6 h are virtual tissues with nitrogen washout half-times of 400 to 615 min. Our model provides a new approach to predicting DCS risk for various decompression profiles. By demonstrating the dependence of DCS risk on body tissue parameters, the model explains why resistance to DCS in mammals increases with a lower body mass and greater specific blood flow in tissues.


Cellular Response to Exponentially Increasing and Decreasing Dose Rates: Implications for Treatment Planning in Targeted Radionuclide Therapy.
The treatment of cancer using targeted radionuclide therapy is of interest to nuclear medicine and radiation oncology because of its potential for killing tumor cells while minimizing dose-limiting toxicities to normal tissue. The ionizing radiations emitted by radiopharmaceuticals deliver radiation absorbed doses over protracted periods of time with continuously varying dose rates. As targeted radionuclide therapy becomes a more prominent part of cancer therapy, accurate models for estimating the biologically effective dose (BED) or equieffective dose (EQD2α/β) will become essential for treatment planning. This study examines the radiobiological impact of the dose rate increase half-time during the uptake phase of the radiopharmaceutical. MDA-MB-231 human breast cancer cells and V79 Chinese hamster lung fibroblasts were irradiated chronically with 662 keV γ rays delivered with time-varying dose rates that are clinically relevant. The temporal dose-rate patterns were: 1. acute, 2. exponential decrease with a half-time of 64 h (Td = 64 h), 3. initial exponential increase to a maximum (half time Ti = 2, 8 or 24 h) followed by exponential decrease (Td = 64 h). Cell survival assays were conducted and surviving fractions were determined. There was a marked reduction in biological effect when Ti was increased. Cell survival data were tested against existing dose-response models to assess their capacity to predict response. Currently accepted models that are used in radiation oncology overestimated BED and EQD2α/β at low-dose rates and underestimated them at high-dose rates. This appears to be caused by an adaptive response arising as a consequence of the initial low-dose-rate phase of exposure. An adaptive response function was derived that yields more accurate BED and EQD2α/β values over the spectrum of dose rates and absorbed doses delivered. Our experimental data demonstrate a marked increase in cell survival when the dose-rate-increase half-time is increased, thereby suggesting an adaptive response arising as a consequence of this phase of exposure. We have modified conventional radiobiological models used in the clinic for brachytherapy and external beams of radiation to account for this phenomenon and facilitate their use for treatment planning in targeted radionuclide therapy.


Equity in healthcare access and service coverage for older people: a scoping review of the conceptual literature.
There is currently no global review of the conceptual literature on the equity of healthcare coverage (including access) for older people. It is important to understand the factors affecting access to health and social care for this group, so that policy and service actions can be taken to reduce potential inequities. A scoping review of published and grey literature was conducted with the aim of summarising how health and social care service access and coverage for older people has been conceptualised. PubMed, MEDLINE, PsycINFO, CINAHL, Web of Science, SciELO, LILACS, BIREME and Global Index Medicus were searched. Selection of sources and data charting were conducted independently by two reviewers. The database searches retrieved 10 517 citations; 32 relevant articles were identified for inclusion from a global evidence base. Data were summarised and a meta-framework and model produced listing concepts specific to equitable health and social care service coverage relating to older people. The meta-framework identified the following relevant factors: acceptability, affordability, appropriateness, availability and resources, awareness, capacity for decision-making, need, personal social and cultural circumstances, physical accessibility. This scoping review is relevant to the development and specification of policy for older people. It conceptualises those factors, such as acceptability and affordability, that affect an older person's ability and capacity to access integrated, person-centred health and social care services in a meaningful way. These factors should be taken into account when seeking to determine whether equity in service use or access is being achieved for older people.


Mechanisms of Retinal Fluid Accumulation and Blood-Retinal Barrier Breakdown.
Macular edema is the swelling of the central portion of the human retina and it is associated with increased retinal thickness. It can be simply defined as an excess of fluid within the retinal tissue. It must be realized that the normal retina possesses a functional extracellular space. With regard to the extracellular volume of the retina, there have been few physiologic studies, but there are reported values of 24.8% for the cerebrum and 23.6% for the cerebellum. It is accepted that the retinal extracellular space is similar to the brain. It is generally agreed that the proximate cause of macular edema and retinal fluid accumulation is a breakdown of the blood-retinal barrier (BRB). When there is a breakdown of the BRB, retinal edema can be interpreted in terms of basic principles of capillary filtration (Starling's law). Therefore, the main factors influencing retinal edema formation are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. Active transport by the retinal pigment epithelium is necessary to remove water that percolates through the retina from intraocular pressure and is also as a safety mechanism against fluid accumulation in disease. Clinical evaluation of the BRB and retinal edema can be performed noninvasively by using an OCT-based method designated OCT-Leakage, which is capable of identifying and quantifying sites of alteration of the BRB, and by mapping sites of low optical reflectivity, i.e., changes in the retinal extracellular fluid.


Rrp4 and Csl4 are needed for efficient degradation but not for polyadenylation of synthetic and natural RNA by the archaeal exosome.
The exosome of the archaeon Sulfolobus solfataricus is a protein complex with phosphorolytic and polyadenylating activity. Little is known about its substrates and the regulation of its functions. We characterized the catalytically active hexameric ring composed of SsoRrp41 and SsoRrp42, and the nine-subunit exosomes containing in addition RNA binding protein SsoRrp4 or SsoCsl4 under various reaction conditions. The exosome synthesized heteropolymeric RNA tails and exhibited the highest in vitro activity at 60-70 degrees C. MgCl(2) was necessary for exosome activity. The two reactions, degradation and polyadenylation of RNA, were inhibited by increasing glycerol and KCl concentrations but were differently influenced by changes in pH and by increasing MgCl(2) concentrations. The three protein complexes with different compositions were similarly influenced by increasing concentrations of glycerol, KCl, and MgCl(2), but the SsoRrp4 exosome behaved differently with respect to pH changes. A 20-nucleotide poly(A) tail enabled the degradation and the polyadenylation of a 16S rRNA-derived transcript by the hexamer. Generally, RNA synthesis by the hexamer was more efficient than RNA phosphorolysis. Single-stranded poly(A) RNA, a heteropolymeric 97-nucleotide transcript, and natural tRNA were quickly polyadenylated, showing that these substrates were bound and their 3'-ends reached the active site. Despite this, their efficient degradation was possible only in the presence of SsoRrp4 or SsoCsl4. Thus, strong substrate binding by SsoRrp4- or SsoCsl4-containing exosomes is more important for phosphorolysis than for tailing of RNA. In summary, the data suggest that subunit composition and Mg(2+) are involved in the regulation of exosome activity.


Human gamma- to beta-globin gene switching in transgenic mice.
Previous studies demonstrated correct tissue- and temporal-specific expression of human gamma- and beta-globin genes in transgenic mice; however, expression was extremely low. When the erythroid-specific DNase I super-hypersensitive (HS) sites that are normally located upstream of the human beta-globin locus were fused individually to gamma- or beta-globin genes, expression increased to endogenous mouse globin levels but temporal specificity was lost. In contrast, when the HS sequences were combined with fragments containing both gamma- and beta-globin genes, correct developmental regulation was restored. We suggest that human gamma- to beta-globin gene switching during development results from competition of individual globin gene family members for interaction with the HS sequences and that factors influencing these competitive interactions determine temporal specificity.