Bio-crude oil from hydrothermal liquefaction of wastewater microalgae in a pilot-scale continuous flow reactor.
To explore the feasibility of scaling up hydrothermal liquefaction (HTL) of algal biomass, a pilot-scale continuous flow reactor (CFR) was operated to produce bio-crude oil from algal biomass cultivated in urban wastewater. The CFR system ran algal slurry (5 wt.% solids loading) at 350 °C and 17 MPa for 4 h without any clogging issues. Bio-crude oil chemistry was characterized by high-resolution Fourier transform mass spectroscopy (FT-MS), proton nuclear magnetic resonance spectroscopy (1H NMR), bomb calorimetry, and elemental analysis. Bio-crude oil yield of 28.1 wt% was obtained with higher heating values of 38-39 MJ/kg. The quality of light bio-crude oil produced from the CFR system was comparable in terms of molecular structures to bio-crude oil produced in a batch reactor.


Primary omental torsion in children.
Primary torsion of the omentum is an unusual cause of an acute abdomen and commonly mimics acute appendicitis. The following report of four obese children is supportive of obesity as a predisposing factor. The paucity of gastrointestinal symptoms, anorexia, nausea, vomiting, and the relatively long duration of symptoms, may increase the index of suspicion. In the majority of cases, the diagnosis is made intraoperatively by digital exploration through the muscle-splitting incision. The torsed omentum is easily delivered through the same incision, and excision results in complete recovery.


Functional Ionic Liquid Crystals.
Ionic liquid crystals have emerged as a new class of functional soft materials in the last two decades, and they exhibit synergistic characteristics of ionic liquids and liquid crystals such as macroscopic orientability, miscibility with various species, phase stability, nanostructural tunability, and polar nanochannel formation. Owing to these characteristics, the structures, properties, and functions of ionic liquid crystals have been a hot topic in materials chemistry, finding various applications including host frameworks for guest binding, separation membranes, ion-/proton-conducting membranes, reaction media, and optoelectronic materials. Although several excellent review articles of ionic liquid crystals have been published recently, they mainly focused on the fundamental aspects, structures, and specific properties of ionic liquid crystals, while these applications of ionic liquid crystals have not yet been discussed at one time. The aim of this feature article is to provide an overview of the applications of ionic liquid crystals in a comprehensive manner.


Investigation of Danshen and related medicinal plants in China.
In China, over 20 Salvia species have been used as Danshen in traditional folk medicine for the treatment of coronary heart diseases and strokes. In order to gain a better understanding of the plants used in this formula, where the plants originate and how the plants are traditionally processed and handled. A field investigation on traditional functions and folk therapeutic uses of these plants was conducted. Based upon interviewing and working with traditional healers, we present the information recorded in detail upon these medicinal plants including the local name, collecting location, growing environment, distribution and therapeutic effects. The current survey revealed 17 original plants used as folk medicine of Danshen in different regions of China. Additionally, HPLC coupled with DAD detection was applied to study the quality of different Danshen samples. The results indicated that the official species of Salvia miltiorrhiza Bunge recorded in Chinese Pharmacopoeia (2005) is the unique species of Danshen that meets all the requirements as described. However, a total of 18 Salvia spp. are collected, used and traded under this same name. In different regions of China, many species in Salvia genus are collected, traded and used as the traditional medicinal plant, Danshen. Based upon this investigation including both the botanical authentication and the chemical characterization of all the collected species. We found that only S. miltiorrhiza meet the requirements set forth and ascribed as the formal Danshen in the Chinese Pharmacopoeia (2005).


Clinical prediction rules for multi surfaces walking independence using the Berg Balance Scale or Mini-Balance Evaluation Systems Test in persons with stroke.
A Clinical prediction rule (CPR) for determining multi surfaces walking independence in persons with stroke has not been established. To develop a CPR for determining multi surfaces walking independence in persons with stroke. This was a multicenter retrospective analysis of 419 persons with stroke. We developed a Berg Balance Scale (BBS)-model CPR combining the BBS, comfortable walking speed (CWS) and cognitive impairment, and a Mini-Balance Evaluation Systems Test (Mini-BESTest)-model CPR combining the Mini-BESTest, CWS, and cognitive impairment. A logistic regression analysis was conducted with multi surfaces walking independence as the dependent variable and each factor as an independent variable. The identified factors were scored (0, 1) based on reported cutoff values. The CPR's accuracy was verified by the area under the curve (AUC). We used a bootstrap method internal validation and calculated the CPR's posttest probability. The logistic regression analysis showed that the BBS, CWS, and cognitive impairment were factors in the BBS model, and the Mini-BESTest was a factor in the Mini-BESTest model. The CPRs were 0-3 points for the BBS model and 0-1 points for the Mini-BESTest model. The AUCs (bootstrap mean AUC) of the CPR score were 0.89 (0.90) for the BBS model and 0.72 (0.72) for the Mini-BESTest model. The negative predictive value (negative likelihood ratio) was 97% (0.054) for CPR scores < 2 for the BBS model and 94% (0.060) for CPR scores < 1 for the Mini-BESTest model. The CPR developed herein is useful for determining multi surfaces walking independence.


Intracranial dural arteriovenous fistula presenting as parkinsonism and cognitive dysfunction.
There are few syndromes of parkinsonism with dementia which can be treated. We report two patients with dural arteriovenous fistula (DAVF) who presented with rapidly progressive parkinsonism and cognitive dysfunction. DAVF are rare lesions resulting from abnormal connections between meningeal arteries and dural sinuses. Angiography in both patients revealed DAVF associated with multiple occlusive changes in the dural venous sinus. This report emphasizes the need for a high level of clinical suspicion to diagnose DAVF and consider it as one of the causes of rapidly progressive cognitive dysfunction in patients with parkinsonism.


Polychromatic action spectrum for the induction of a mycosporine-like amino acid in a rice-field cyanobacterium, Anabaena sp.
A polychromatic action spectrum for the induction of an ultraviolet-absorbing/screening mycosporine-like amino acid (MAA) has been determined in a filamentous and heterocystous nitrogen-fixing rice-field cyanobacterium, Anabaena sp. High-performance liquid chromatographic (HPLC) studies revealed the presence of only one type of MAA, which was identified as shinorine, a bisubstituted MAA containing both glycine and serine groups having a retention time at 2.8 min and an absorption maximum at 334 nm. Exposure of cultures to simulated solar radiation in combination with various cut-off filters (WG 280, 295, 305, 320, 335, 345, GG 400, 420, 455, 475, OG 515, 530, 570, RG 645, 665 and a broad-band filter, UG 11) clearly revealed that the induction of the MAA takes place only in the UV range. Photosynthetic active radiation (PAR) had no significant impact on MAA induction. The ratio of the absorption at 334 nm (shinorine) to 665 nm (chlorophyll a) and the action spectrum also showed the induction of MAA to be UV dependent peaking in the UV-B range at around 290 nm. The results indicate that the studied cyanobacterium, Anabaena sp. may protect itself from deleterious short wavelength solar radiation by its ability to synthesize a mycosporine-like amino acid in response to UV-B radiation and thereby screen the negative effects of UV-B.


The effects of PPARδ agonist and zinc on ovariectomized rats' vagina.
This study aimed to measure the effects of peroxisome proliferator-activated receptor-δ (PPARδ) agonist GW501516 (GW) and zinc sulfate (ZS) on ovariectomized rats' vaginal histomorphology and collagen expression. Two weeks after ovariectomy, rats received daily treatment with vaginal suppositories containing placebo, ZS, GW, ZS with GW, or estradiol for 2 weeks. Macroscopic measurements were taken and the midsection of the vagina was used for histology. Immunofluorescence was performed with antibodies against collagen I, III, and anti-actin or collagen I and V and anti-actin. Gene expression analysis of 3 collagen genes was performed by qRT-PCR. Macroscopic measurements revealed that the genital hiatus was narrower in the ZS and ZS with GW groups, and the vagina was significantly longer in the animals treated with GW, ZS with GW, and estradiol compared to the placebo group. Microscopic measurements of the vaginal layers showed that the lamina propria and the vaginal muscularis were significantly thicker in the ZS and ZS with GW group compared to the placebo.The ratio of vaginal Col1a1/Col3a1 mRNA expression was significantly up-regulated by ZS with GW compared to placebo, whereas the ratio of vaginal Col1a1/Col5a1 expression was significantly up-regulated by ZS, GW, and ZS with GW. The ratio of vaginal collagen I/III protein expression was significantly up-regulated by ZS and ZS with GW, whereas the ratio of vaginal collagen I/V expression was significantly up-regulated by estradiol, ZS, and ZS with GW compared to control. Vaginal suppositories containing zinc and PPARδ agonist significantly altered the vagina of ovariectomized rats.


Clinical characteristics analysis of sinonasal diffuse large B-cell lymphoma and extranodal NK/T-cell lymphoma.
Extranodal NK/T-cell lymphoma (ENKL) was the most common sinonasal lymphoma at our hospital. ENKL occurs at a younger age, and is more prevalent in the nasal cavity. ENKL had a lower Ann Arbor stage, and a better prognosis than diffuse large B-cell lymphoma (DLBLC).


Differences in dopamine release and metabolism in rat striatal subregions following acute clozapine using in vivo microdialysis.
This study examined and compared the effects of acute clozapine administration over a range of doses on the release of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in dorsolateral and fundus striata. Basal extracellular DA levels were significantly higher in the dorsolateral striatum. However, DOPAC levels were similar in both regions. Acute treatment with clozapine (40 mg/kg) was associated with an increase in extracellular dopamine in the dorsolateral striatum but not in the fundus. In contrast, an increase in extracellular DOPAC was seen in both regions following all doses of the drug; however, clozapine was more potent in the dorsolateral striatum than in the fundus. These results illustrate the functional heterogeneity of the striatum and in addition, indicate a possible dissociation between the effect of acute clozapine on DA release and DA metabolism.


Precision of GE Lunar iDXA for the measurement of total and regional body composition in nonobese adults.
Dual-energy X-ray absorptiometry (DXA) is a well-accepted technique for measuring body composition. Knowledge of measurement precision is critical for monitoring of changes in bone mineral content (BMC), and fat and lean masses. The purpose of this study was to characterize in vivo precision of total body and regional body composition parameters using the GE Lunar iDXA (GE Healthcare Lunar, Madison, WI) system in a sample of nonobese subjects. We also evaluated the difference between expert and automatic region-of-interest (ROI) analysis on body composition precision. To this end, 2 total body scans were performed on each subject with repositioning between scans. Total body precision for BMC, fat and lean mass were 0.5%, 1.0%, and 0.5% coefficient of variation (CV), respectively. Regional body composition precision error was less than 2.5% CV for all regions except arms. Precision error was higher for the arms (CV: BMC 1.5%; fat mass 2.8%; lean mass 1.6%), likely owing to the placement of arms relative to torso leading to differences in ROI. There was a significant correlation between auto ROI and expert ROI (r>0.99). Small, but statistically significant differences were found between auto and manual ROI. Differences were small in total body, leg, trunk, and android and gynoid regions (0.004-2.8%), but larger in arm region (3.0-6.3%). Total body and regional precision for iDXA are small and it is suggested that iDXA may be useful for monitoring changes in body composition during longitudinal trials.


Guiding principles for the implementation of non-animal safety assessment approaches for cosmetics: skin sensitisation.
Characterisation of skin sensitisation potential is a key endpoint for the safety assessment of cosmetic ingredients especially when significant dermal exposure to an ingredient is expected. At present the mouse local lymph node assay (LLNA) remains the 'gold standard' test method for this purpose however non-animal test methods are under development that aim to replace the need for new animal test data. COLIPA (the European Cosmetics Association) funds an extensive programme of skin sensitisation research, method development and method evaluation and helped coordinate the early evaluation of the three test methods currently undergoing pre-validation. In May 2010, a COLIPA scientific meeting was held to analyse to what extent skin sensitisation safety assessments for cosmetic ingredients can be made in the absence of animal data. In order to propose guiding principles for the application and further development of non-animal safety assessment strategies it was evaluated how and when non-animal test methods, predictions based on physico-chemical properties (including in silico tools), threshold concepts and weight-of-evidence based hazard characterisation could be used to enable safety decisions. Generation and assessment of potency information from alternative tools which at present is predominantly derived from the LLNA is considered the future key research area.


[Basal ganglia deep-brain stimulation for treatment of drug-resistant epilepsy: review and current data].
The surgical treatment of intractable epilepsies involving eloquent areas of the cortex is still challenging. Deep-brain stimulation could be an alternative to resective surgery because it can modulate the remote control systems of epilepsy, such as the thalamus and basal ganglia. The surgical experience acquired in the field of movement disorder surgery and the low morbidity of this technic could allow one to apply DBS to intractable epilepsies, such as generalized, motor and bitemporal epilepsies. Here we discuss the main experimental and clinical data reported so far in the literature and taken from our own experience.


Postnatal MRI for CDH: A pictorial review of late-presenting and recurrent diaphragmatic defects.
Late-presenting or recurrent diaphragmatic defects can pose a diagnostic challenge due to varying clinical presentations. Current diagnostic approaches include plain film radiograph for initial assessment, with other imaging modalities such as fluoroscopy, ultrasound, CT and MRI mainly utilized for troubleshooting. As a radiation-free modality, MRI can provide a more definitive diagnosis in particular cases due to its ability to visualize discontinuity of the diaphragm, distinguishing it from eventration. MRI can also accurately characterize hernia contents, defect location and size. We present our MRI technique and review cases of different hernia types with relevant discussion of the imaging findings and correlation with intraoperative findings. MRI can be a useful diagnostic tool in the assessment of late presenting or recurrent diaphragmatic hernias.


Quadrupolar relaxation of hyperpolarized krypton-83 as a probe for surfaces.
This work reports the first systematic study of relaxation experienced by the hyperpolarized (hp) noble gas isotope (83)Kr (I=9/2) in contact with surfaces. The spin-lattice relaxation of (83)Kr is found to depend strongly on the chemical composition of the surfaces in the vicinity of the gas. This effect is caused by quadrupolar interactions during brief periods of surface adsorption that are the dominating source of longitudinal spin relaxation in the (83)Kr atoms. Simple model systems of closest packed glass beads with uniform but variable bead sizes are used for the relaxation measurements. The observed relaxation rates depend strongly on the chemical treatment of the glass surfaces and on the surface to volume ratio. Hp (83)Kr NMR relaxation measurements of porous polymers with pore sizes of 70-250 microm demonstrate the potential use of this new technique for material sciences applications.


Patients' preferences for receiving clinical information and participating in decision-making in Iran.
This study, the first of its kind in Iran, was to assess Iranian patients' preferences for receiving information and participating in decision-making and to evaluate their satisfaction with how medical information is given to them and with their participation in decision-making at present. 299 of 312 eligible patients admitted to general internal medicine or surgery wards from May to December 2006 were interviewed according to a structured questionnaire. The questionnaire contained questions about patients' preferences regarding four domains of information and their participation in decision-making. Patients' responses were measured on a visual analogue scale graded from 1 to 10. The mean (SD) score for desire to receive information was 8.88 out of 10 (1.5) and for participation in medical decision-making was 7.75 out of 10 (3). The desire to receive information was greater in women than men (9.0 (1.5) vs 7.8 (1.4), p = 0.025). It was also correlated with their education (r = 0.2, p = 0.001) and their estimation of the severity of their own disease (r = 0.13, p = 0.027). The score for preference to participate in decision-making was higher in women than in men (7.95 (2.8) and 7.0 (3.2), respectively; beta = 0.8, p = 0.022) and was negatively correlated with education (r = -0.14, p = 0.015). This study shows that Iranian patients are highly interested in receiving information about their condition and participating in clinical decision-making. No predictive variable for such attitudes was found; therefore, the only way for the physician to recognise patients' desire is to ask them explicitly.


Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome)
Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases.


A dual role for UVRAG in maintaining chromosomal stability independent of autophagy.
Autophagy defects have recently been associated with chromosomal instability, a hallmark of human cancer. However, the functional specificity and mechanism of action of autophagy-related factors in genome stability remain elusive. Here we report that UVRAG, an autophagic tumor suppressor, plays a dual role in chromosomal stability, surprisingly independent of autophagy. We establish that UVRAG promotes DNA double-strand-break repair by directly binding and activating DNA-PK in nonhomologous end joining. Disruption of UVRAG increases genetic instability and sensitivity of cells to irradiation. Furthermore, UVRAG was also found to be localized at centrosomes and physically associated with CEP63, an integral component of centrosomes. Disruption of the association of UVRAG with centrosomes causes centrosome instability and aneuploidy. UVRAG thus represents an autophagy-related molecular factor that also has a convergent role in patrolling both the structural integrity and proper segregation of chromosomes, which may confer autophagy-independent tumor suppressor activity.


Bacterial synergy in pelvic inflammatory disease.
Polymicrobial aerobic and anaerobic flora are responsible for pelvic inflammatory disease (PID). The most frequent pathogens appear to be Neisseria gonorrhoea and anaerobic bacteria (most commonly anaerobic cocci and Bacteroides sp.). Recent studies have demonstrated the recovery of Chlamydia trachomatis in up to a third of these infections. Although N. gonorrhoea is frequently recovered from cervical cultures, it is less commonly recovered from intra-abdominal sites. Recent studies have demonstrated the in-vivo synergistic relationship between N. gonorrhoeae and Bacteroides fragilis. The growth of each component of the mixed infection was enhanced when these were present together in an abscess. Furthermore, the emergence of encapsulated strains was enhanced in these infections. This synergy enables the organisms to cause more severe local and systemic damage to the host. Therapeutic intervention should include the use of antimicrobial agents effective against both the aerobic and anaerobic components of the mixed infection. Unless such therapy is given, the infection may persist. It is also recommended to use antimicrobials that possess synergy between them against the bacterial pathogens. Agents effective against the anaerobic pathogens are metronidazole, clindamycin and cefoxitin. Antimicrobials effective against the Gram-positive aerobic pathogens and N. gonorrhoeae are spiramycin and penicillins. Aminoglycosides or third generation cephalosporins are effective against Gram-negative enterics. The combination of metronidazole and spiramycin has shown to be synergistic against mixed infections of Bacteroides sp. and N. gonorrhoeae.


Epidemiological investigation of canine coronavirus infection in Chinese domestic dogs: A systematic review and data synthesis.
Canine enteric coronavirus (CCoV) is a pathogenic virus that infects dogs worldwide, causing enteric issues and causing harm to the dog industry and dogs. Although CCoV is not recognized as a highly lethal canine intestinal pathogen, it has been reported that CCoV is significantly associated with canine diarrhea in dogs. CCoV is a common health problem in dogs, attracting major concern from veterinarians and dog owners across China. In this study, we summarized the prevalence and epidemiological characteristics of CCoV in dogs in mainland China. The study revealed that the pooled prevalence of CCoV infection was 33%, and which associated with age, but not with sex, season and immunization status. In addition, the study also further suggested that CCoV-II was the predominant CCoV subtype in Chinese dogs. This study will provide valuable information for CCoV infections across China and other countries. Furthermore, this study also suggested that continuous surveillance and epidemiological studies of CCoV are necessary.


Influence of protein flexibility on the redox potential of rubredoxin: energy minimization studies.
A theoretical investigation of the protein contribution to the redox potential of the iron-sulfur protein rubredoxin is presented. Structures of the oxidized and reduced forms of the protein were obtained by energy minimizing the oxidized crystal structure of Clostridium pasteurianum rubredoxin with appropriate charges and parameters. By including 102 crystal waters, structures close to the original crystal structure were obtained (rms difference of 1.16 A), even with extensive minimization, thus allowing accurate calculations of comparative energies. Our calculations indicate an energy change of about -60 kcal/mol (2.58 eV) in the protein alone upon reduction. This energy change was due to both the change in charge of the redox site and the subsequent relaxation of the protein. An energy minimization procedure for the relaxation gives rms differences between the oxidized and reduced states of about 0.2 A. The changes were small and occurred in both the backbone and sidechain mainly near the Fe-S center but contributed about -16 kcal/mol (0.69 eV) to the total protein contribution. Although the neglect of certain effects such as electronic polarization may make the relaxation energies calculated an upper limit, the results indicate that protein relaxation contributes substantially to the redox potential.


Evidence of beneficial effect of physical therapy after lower-extremity trauma.
To examine the effect of physical therapy (PT) use on a range of measures of physical impairment in a cohort of patients with lower-extremity trauma. Longitudinal, observational study of patients with severe lower-extremity trauma. Patients were interviewed by a research coordinator and examined by an orthopedic surgeon and a physical therapist during initial admission and at 3, 6, 12, and 24 months postdischarge. Eight level I trauma centers. Patients (N=382) whose legs were salvaged after limb-threatening trauma to the lower limb. Not applicable. Unmet need for PT was assessed from 2 perspectives: an orthopedic surgeon and a physical therapist independently evaluated each patient and were asked whether the patient would benefit from PT. Patients classified by these health professionals as needing PT services over a given period and who reported receiving no PT at the end of that period were classified as having unmet need as evaluated by the orthopedic surgeon or physical therapist for that follow-up period. Multiple variable regression techniques were used to compare improvement in 5 measures of physical impairment and functional limitation between the met and unmet need groups over the periods of 3 to 6, 6 to 12, and 12 to 24 months: percentage of impairment in knee and ankle range of motion (ROM), reciprocal stair climbing pattern, gait deviations when walking, self-selected walking speed greater than 1.2 m/s (4 ft/s), and the mobility subscores of the FIM instrument. Patients with unmet need for PT as assessed by a physical therapist were statistically significantly less likely to improve in all 5 of the selected domains of physical impairment and functional limitation than patients whose PT need was met. These results remained constant after adjustment for patient sociodemographic, personality, and social resources, as well as injury and treatment characteristics, reported pain intensity, and impairment level at the beginning of the study period. Patients with unmet need for PT as evaluated by an orthopedic surgeon were significantly worse off than patients with met need in only 1 of the 5 selected measures (ROM). The results are consistent with a beneficial effect of PT after lower-extremity trauma. The results point to a need for improved standards for the prescription of PT services, and highlight the importance of involving a PT professional in the prescribing process.


Creating a model of diseased artery damage and failure from healthy porcine aorta.
Large quantities of diseased tissue are required in the research and development of new generations of medical devices, for example for use in physical testing. However, these are difficult to obtain. In contrast, porcine arteries are readily available as they are regarded as waste. Therefore, reliable means of creating from porcine tissue physical models of diseased human tissue that emulate well the associated mechanical changes would be valuable. To this end, we studied the effect on mechanical response of treating porcine thoracic aorta with collagenase, elastase and glutaraldehyde. The alterations in mechanical and failure properties were assessed via uniaxial tension testing. A constitutive model composed of the Gasser-Ogden-Holzapfel model, for elastic response, and a continuum damage model, for the failure, was also employed to provide a further basis for comparison (Calvo and Peña, 2006; Gasser et al., 2006). For the concentrations used here it was found that: collagenase treated samples showed decreased fracture stress in the axial direction only; elastase treated samples showed increased fracture stress in the circumferential direction only; and glutaraldehyde samples showed no change in either direction. With respect to the proposed constitutive model, both collagenase and elastase had a strong effect on the fibre-related terms. The model more closely captured the tissue response in the circumferential direction, due to the smoother and sharper transition from damage initiation to complete failure in this direction. Finally, comparison of the results with those of tensile tests on diseased tissues suggests that these treatments indeed provide a basis for creation of physical models of diseased arteries.


Associations of chest X-ray trajectories, smoking, and the risk of lung cancer in two population-based cohort studies.
Despite the increasing use of computed tomography (CT), chest X-ray (CXR) remains the first-line investigation for suspected lung cancer (LC) in primary care. However, the associations of CXR trajectories, smoking and LC risk remain unknown. A total of 52,486 participants from the PLCO and 22,194 participants from the NLST were included. The associations of CXR trajectories with LC risk were evaluated with multivariable COX regression models and pooled with meta-analyses. Further analyses were conducted to explore the stratified associations by smoking status and the factors associated with progression and regression in CXR. Compared to stable negative CXR (CXRSN), HRs (95%CIs) of LC incidence were 2.88(1.50-5.52), 3.86(2.03-7.35), and 1.08(0.80-1.46) for gain of positive CXR (CXRGP), stable positive CXR (CXRSP), and loss of positive CXR (CXRLP), while the risk of LC mortality were 1.58(1.33-1.87), 2.56(1.53-4.29), and 1.05(0.89-1.25). Similar trends were observed across different smoking status. However, LC risk with CXRGP overweighed that with CXRSP among ever smokers [2.95(2.25-3.88) vs. 2.59(1.33-5.02)] and current smokers [2.33(1.70-3.18) vs. 2.26(1.06-4.83)]. Moreover, compared to CXRSN among never smokers, even no progression in CXR, the HRs(95%CIs) of LC incidence were 7.39(5.60-9.75) and 31.45(23.58-41.95) for ever and current smokers, while risks of LC mortality were 6.30(5.07-7.81) and 27.17(21.65-34.11). If participants gained positive CXR, LC incidence risk significantly climbed to 22.04(15.37-31.60) and 71.97(48.82-106.09) for ever and current smokers, while LC mortality risk climbed to 11.90(8.58-16.50) and 38.92(27.04-56.02). CXRLP was associated with decreased LC risk. However, even smokers lost their positive CXR, and the increased risks of LC incidence and mortality did not decrease to non-significant level. Additionally, smoking was significantly associated with increased risk of CXRGP but not CXRLP. LC risk differed across CXR trajectories and would be modified by smoking status. Comprehensive intervention incorporating CXR trajectories and smoking status should be recommended to reduce LC risk.


p-Phenylene Diisothiocyanate-Based Covalent Immobilization of β-d-Galactosidase and Determination of Enzyme Activity by Cleavage of X-Gal and ONPG on Solid Support.
Herein, we present the immobilization of a technical grade β-d-galactosidase on amino-functionalized microtiter plates. Afterward, we transferred the results to a resin-based approach. For the covalent binding of the enzyme, an amino-functionalized microtiter plate was prefunctionalized with 1,4-phenylendiisothiocyanate. The cleavage of the substrate 5-bromo-4-chloro-3-indoxyl-β-d-galactopyranoside (X-Gal) produces a deep blue dye, which was quantified in a microtiter plate reader at 595 nm. The maximum reaction rates and the Michaelis-Menten constant were calculated. In addition, the unwanted blue precipitate formed during the experiments could be minimized by optimizing the experiments. When transferring the immobilization method to Rink amide resin, o-nitrophenyl-β-d-galactopyranoside was used as the substrate and the measurement was carried out in a photometer at 420 nm.


Longitudinal melonychia: clinical evaluation and biopsy technique.
Longitudinal melonychia is a brown streaking of the nailbed. It is often benign but can be a subungual melanoma. Subungual melanoma is a rare malignancy. Diagnosis is often delayed, resulting in a higher staging and poorer prognosis than other cutaneous melanomas. We provide an update on the evaluation of longitudinal melonychia and biopsy technique.


Community-based rehabilitation implementation for people with disabilities in South Africa: a protocol for a scoping review.
People with disabilities (PWDs) remain among the poorest and least empowered population. They experience limited access to basic services, especially in low- and middle-income countries (LMIC). The infringement of their human rights remains at an alarming level, despite the availability of the community-based rehabilitation (CBR) strategy and the United Nations Convention on the Rights of People with Disabilities (UNCRPD). CBR, as a strategy for poverty alleviation, social inclusion and equalisation of opportunity, has broadened its scope from a mere strategy for access to health and rehabilitation services to include education, livelihood, social inclusivity and empowerment. CBR is implemented across the world in the majority of LMIC signatories to the UNCRPD. South Africa is among the countries that are implementing CBR. However, the extent and the nature of implementation is not known. This study, therefore, aims to map out the empirical evidence of the implementation of CBR in South Africa. The study is a scoping review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extended for Scoping Review (PRISMA-ScR) methodology. The information will be extracted and captured on a data charting template that will be used through each phase of the study. The review will be guided by the following research question validated by the amended population-concept-context framework according to the Joanna Briggs Institute methodology for scoping reviews: 'An investigation into CBR implementation in South Africa.' The search will be conducted in the following electronic databases Google Scholar, PubMed, Medline, and Cochrane, etc, using Boolean logic. Restrictions will be set for years (Jan. 2009-Dec. 2019), English language peer-reviewed studies based on South Africa. The search output will be screened for primary studies on Community based rehabilitation in South Africa. Two independent reviewers will conduct title and abstract screening to identify potential eligible studies. After which full-text screening on the potential eligible studies and assessed for inclusion by the two independent reviewers. The Mixed Method Appraisal Tool will be applied to assess the quality of the studies included in the review. The gathered evidence from the selected studies will be discussed in relation to the research questions using a narrative to identify and explore emergent themes. The review will provide a baseline of evidence on the implementation of CBR and will highlight gaps regarding the implementation of CBR in a South African Context. The gaps identified will be used to develop a framework that will guide implementation of CBR in South Africa.


Association of blood metals with serum sex hormones in adults: A cross-sectional study.
Heavy metals such as lead, mercury, and cadmium have been identified to have negative impacts on human health. Although the individual effects of these metals have been extensively researched, the present study aims to explore their combined effects and their association with serum sex hormones among adults. Data for this study were obtained from the general adult population of the 2013-2016 National Health and Nutrition Survey (NHANES) and included five metal (mercury, cadmium, manganese, lead, and selenium) exposures and three sex hormones (total testosterone [TT], estradiol [E2], and sex hormone-binding globulin [SHBG]) levels. The free androgen index (FAI) and TT/E2 ratio were also calculated. The relationships between blood metals and serum sex hormones were analysed using linear regression and restricted cubic spline regression. The effect of blood metal mixtures on sex hormone levels was examined using the quantile g-computation (qgcomp) model. There were 3,499 participants in this study, including 1,940 males and 1,559 females. In males, positive relationships between blood cadmium and serum SHBG (β=0.049 [0.006, 0.093]), lead and SHBG (β=0.040 [0.002, 0.079]), manganese and FAI (β=0.080 [0.016, 0.144]), and selenium and FAI (β=0.278 [0.054, 0.502]) were observed. In contrast, manganese and SHBG (β=-0.137 [-0.237, -0.037]), selenium and SHBG (β=-0.281 [-0.533, -0.028]), and manganese and TT/E2 ratio (β=-0.094 [-0.158, -0.029]) were negative associations. In females, blood cadmium and serum TT (β=0.082 [0.023, 0.141]), manganese and E2 (β=0.282 [0.072, 0.493]), cadmium and SHBG (β=0.146 [0.089, 0.203]), lead and SHBG (β=0.163 [0.095, 0.231]), and lead and TT/E2 ratio (β=0.174 [0.056, 0.292]) were positive relationships, while lead and E2 (β=-0.168 [-0.315, -0.021]) and FAI (β=-0.157 [-0.228, -0.086]) were negative associations. This correlation was stronger among elderly women (>50 years old). The qgcomp analysis revealed that the positive effect of mixed metals on SHBG was mainly driven by cadmium, while the negative effect of mixed metals on FAI was mainly driven by lead. Our findings indicate that exposure to heavy metals may disrupt hormonal homeostasis in adults, particularly in older women.


Herald Cell: The Gateway to Posterior Tympanotomy-A Cadaveric Study.
Posterior tympanotomy is the avenue to the facial recess of the middle ear from mastoid antrum. The entry into the facial recess in many cases is heralded by a distinct air cell before approaching the facial-chordal plane. The current study was undertaken to determine the prevalence of this 'Herald Cell' in an adult cadaveric population. It was a human cadaveric temporal bone dissection study. The bones were dissected to carry out cortical mastoidectomy and posterior tympanotomy using standard otologic drills under microscopic visualization (Leica M320 F12). Appropriate snapshots were taken to document the presence or absence of Herald cell. A total of 51 temporal bones were dissected (26 right, 25 left sided). The Herald cell was found to be present in 22 bones (43.1%). Herald cell, when present, is a convenient and reliable landmark to carry out a safe posterior tympanotomy.


Isolation of a novel O-linked, sulfated polysaccharide of high molecular weight from an ovarian cyst glycoprotein having blood group "A" activity.
Treatment of a blood group A-active ovarian cyst mucin glycoprotein with alkaline borohydride under conditions expected to cleave O-glycosidic linkages between carbohydrate and peptide releases a sulfated polysaccharide of average molecular weight 20,000. Its peptide and mannose content is less than 1%, and carbohydrate analysis gives Fuc/GalNAc/Gal/GlcNAc in the ratio of 1:1:2.2:2.2. Galactosaminitol is recovered at the level of one residue per 112-residue average polysaccharide chain. The 13C- and 1H-NMR spectra show that the polysaccharide has side chains whose non-reducing terminals have the blood group A structure on a type 1 chain: (Formula: see text). Methylation analysis confirms the presence of these blood group A type 1 sidechains as well as 4-substituted GlcNAc, 3-substituted galactose and 3,6-substituted galactose branch points. Periodate oxidation removes all the fucose and GalNAc from the non-reducing terminal but leaves intact the backbone composed of beta-linked Gal and GlcNAc, as would be expected for a polylactosamine. Although the native polysaccharide is resistant to endo-beta-galactosidase digestion, the product of periodate degradation is partially digested, giving a 30% yield of a trisaccharide shown by 1H-NMR spectroscopy to be: Gal(beta 1----3)GlcNAc(beta 1----3)Gal We conclude that this is a high molecular weight sulfated polysaccharide which is related to the asparagine-linked polylactosamine chains of cell surface glycoproteins which have been implicated in cell differentiation. However, the blood group A polysaccharide from the ovarian cyst mucin is unique in several respects. It is linked to the protein by an O-glycosidic bond rather than the N-asparagine linkage of the previously known polylactosamines which have a trimannosyl core, and its blood group A side chains are on a type 1 core rather than type 2 which is found on other polylactosamines.


Anti-serotonin action in combination with noradrenaline-stimulating action is important for inhibiting muricide in midbrain raphe-lesioned rats.
The present study was designed to examine the possible involvement of both an anti-serotonin action and a catecholamine-stimulating action in the mechanism of the inhibition of the muricide in rats with lesions of the midbrain raphe. Serotonin antagonists, such as cyproheptadine (10 mg/kg), cinanserin (10 mg/kg) and pirenperone (1 mg/kg), given alone showed little suppression of muricide in rats with raphe lesions, although the first two drugs were inhibitory at very large doses. Methamphetamine showed no inhibition of muricide at 0.32 mg/kg (i.p.), but exerted a marked inhibition of muricide when combined with the above serotonin antagonists. In addition, the dose-response curve for cyproheptadine and cinanserin was shifted markedly to the left when combined with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) (100 mg/kg i.p.), but not with lisuride (0.32 mg/kg i.p.). Similarly, pirenperone produced a marked inhibition of muricide at doses of 0.32-1.8 mg/kg (i.p.) when combined with L-threo-DOPS, but not when combined with lisuride. These results suggest that the combination of an anti-serotonin action with noradrenergic activation is important for inhibiting muricide, at least in rats with raphe lesions. A similar mechanism also seems to be valid for the anti-muricidal effect of antidepressant drugs.


Effect of the CYP2C9*3 allele on lornoxicam metabolism.
We investigated whether the CYP2C9 genotypes would affect lornoxicam metabolism in healthy volunteers. Twelve healthy volunteers who had been genotyped for CYP2C9 gene were selected to participate in our study. After 8 mg lornoxicam was taken, blood samples were drawn from 0 to 36 h. The plasma concentrations of lornoxicam and 5'-hydroxylornoxicam were determined by HPLC method. 5'-hydroxylornoxicam was purified from rabbits'urine by semi-preparative HPLC. Lornoxicam and 5'-hydroxylornoxicam both exhibit CYP2C9 genotype-dependent pharmacokinetic profiles. The area under the plasma concentration-time curve (AUC) of lornoxicam increased by 60 +/- 9.78% (P <0.05) and the AUC of 5'-hydroxylornoxicam decreased by 65 +/- 11.75% (p <0.001) in heterozygous CYP2C9*1/*3 subjects (n=6) compared with CYP2C9*1/*1 group (n=6). t1/2 value of lornoxicam and 5'-hydroxylornoxicam prolonged by 39 +/- 8.35% and curtailed by 59 +/- 6.83% respectively in CYP2C9*1/*3 subjects. But no significant differences in Tmax of lornoxicam and 5'-hydroxylornoxicam were observed between these 2 genotypes. In addition, for the first time we exploit the purification method for 5'-hydroxylornoxicam from rabbits' urine. The CYP2C9*3 allele significantly affected the metabolism of lornoxicam. The pharmacokinetic parameters of both lornoxicam and 5'-hydroxylornoxicam were significantly different between these 2 genotypes.


Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review.
Although there is substantial evidence of differential hypothalamic-pituitary-adrenal (HPA) axis activity in both generalized and abdominal obesity, consistent trends in obesity-related HPA axis perturbations have yet to be identified. To systematically review the existing literature on HPA activity in obesity, identify possible explanations for inconsistencies in the literature, and suggest methodological improvements for future study. Included papers used Pubmed, Google Scholar, and the University of California Library search engines with search terms body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, sagittal diameter, abdominal versus peripheral body fat distribution, body fat percentage, DEXA, abdominal obesity, and cortisol with terms awakening response, slope, total daily output, reactivity, feedback sensitivity, long-term output, and 11β-HSD expression. Empirical research papers were eligible provided that they included at least one type of obesity (general or abdominal), measured at least one relevant cortisol parameter, and a priori tested for a relationship between obesity and cortisol. A general pattern of findings emerged where greater abdominal fat is associated with greater responsivity of the HPA axis, reflected in morning awakening and acute stress reactivity, but some studies did show underresponsiveness. When examined in adipocytes, there is a clear upregulation of cortisol output (due to greater expression of 11β-HSD1), but in hepatic tissue this cortisol is downregulated. Overall obesity (BMI) appears to also be related to a hyperresponsive HPA axis in many but not all studies, such as when acute reactivity is examined. The reviewed literature contains numerous inconsistencies and contradictions in research methodologies, sample characteristics, and results, which partially precluded the development of clear and reliable patterns of dysregulation in each investigated cortisol parameter. The literature to date is inconclusive, which may well arise from differential effects of generalized obesity vs. abdominal obesity or from modulators such as sex, sex hormones, and chronic stress. While the relationship between obesity and adipocyte cortisol seems to be clear, further research is warranted to understand how adipocyte cortisol metabolism influences circulating cortisol levels and to establish consistent patterns of perturbations in adrenal cortisol activity in both generalized and abdominal obesity.


Cu(II) and Zn(II) ions alter the dynamics and distribution of Mn(II) in cultured chick glial cells.
Previous studies revealed that Mn(II) is accumulated in cultured glial cells to concentrations far above those present in whole brain or in culture medium. The data indicated that Mn(II) moves across the plasma membrane into the cytoplasm by facilitated diffusion or counter-ion transport with Ca(II), then into mitochondria by active transport. The fact that 1-10 microM Mn(II) ions activate brain glutamine synthetase makes important the regulation of Mn(II) transport in the CNS. Since Cu(II) and Zn(II) caused significant changes in the accumulation of Mn(II) by glia, the mechanisms by which these ions alter the uptake and efflux of Mn(II) ions has been investigated systematically under chemically defined conditions. The kinetics of [54MN]-Mn(II) uptake and efflux were determined and compared under four different sets of conditions: no adducts, Cu(II) or Zn(II) added externally, and with cells preloaded with Cu(II) or Zn(II) in the presence and absence of external added metal ions. Zn(II) ions inhibit the initial velocity of Mn(II) uptake, increase total Mn(II) accumulated, but do not alter the rate or extent Mn(II) efflux. Cu(II) ions increase both the initial velocity and the net Mn(II) accumulated by glia, with little effect on rate or extent of Mn(II) efflux. These results predict that increases in Cu(II) or Zn(II) levels may also increase the steady-state levels of Mn(II) in the cytoplasmic fraction of glial cells, which may in turn alter the activity of Mn(II)-sensitive enzymes in this cell compartment.


Isatin analogs as novel inhibitors of Candida spp. β-carbonic anhydrase enzymes.
Enzyme inhibition data of structurally novel isatin-containing sulfonamides were determined for two carbonic anhydrases (CAs, EC 220.127.116.11) from pathogenic Candida species (CaNce103 from C. albicans and CgNce103 from C. glabrata). The compounds show KI values in the low nanomolar range for the fungal CAs, while they have significantly higher KI values for the human CAs. Homology models were constructed for the CaNce103 and CgNce103 and subsequently the ligands were docked into these models to rationalize their enzyme inhibitory properties.


Characterization of sarcoplasmic reticulum in skinned muscle cultures.
The plasma membranes of chick or rat skeletal muscles, grown in cell culture, were made permeable with saponin in a solution lacking calcium. The cells were then supplied with a medium resembling the cytosol and the ATP-dependent Ca2+ sequestration was performed. Based on the low concentration of free Ca2+ in the medium (below 5 microM), the presence of mitochondrial inhibitors and the effect of drugs that interfere with sarcoplasmic reticulum (SR) function, we assume that the measured Ca2+ accumulation expresses SR function on the saponin-treated myotubes. The development of the SR in muscle cultures is augmented as myogenesis proceeds and depends on its occurrence. Whereas creatine kinase activity is elevated immediately following cell fusion, there is a delay of at least 1 day between myoblast fusion and the increase in Ca2+ accumulation in the SR. Thyroxine or triiodothyronine caused an inhibition of Ca2+ accumulation in rat or chick muscle cultures. This inhibition could explain some of the muscle abnormalities caused by excess of thyroid hormones. A comparison was made between a white-type (fast) and heterogeneous muscle, differentiated in cell culture. There was no significant difference in SR function, indicating the important role of innervation in specifying the properties of muscle fiber types.


In vitro and in vivo correlation of skin and cellular responses to nucleic acid delivery.
Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immunogenicity of skin, we correlated the effects of pDNA electrotransfer to fibroblasts and keratinocytes to mouse skin using reverse transcription real-time PCR (RT-qPCR) and several types of protein quantification. After pDNA electrotransfer, the mRNAs of the putative DNA sensors DEAD (AspGlu-Ala-Asp) box polypeptide 60 (Ddx60), absent in melanoma 2 (Aim2), Z-DNA binding protein 1 (Zbp1), interferon activated gene 202 (Ifi202), and interferon-inducible protein 204 (Ifi204) were upregulated in keratinocytes, while Ddx60, Zbp1 and Ifi204 were upregulated in fibroblasts. Increased levels of the mRNAs and proteins of several cytokines and chemokines were detected and varied based on cell type. Mouse skin experiments in vivo confirmed our in vitro results with increased expression of putative DNA sensor mRNAs and of the mRNAs and proteins of several cytokines and chemokines. Finally, with immunofluorescent staining, we demonstrated that skin keratinocytes, fibroblasts and macrophages contribute to the immune response observed after pDNA electrotransfer.


Reiki therapy: the benefits to a nurse/Reiki practitioner.
This study evaluates how nurses who gave Reiki therapy perceived the benefit of this therapy on their clients and on themselves concurrently as providers of the therapy. As an adjunct, the study's purpose was to enhance the understanding and credibility of nurse/Reiki practitioners.


Atypical Histiocytosis in Red Squirrels (Sciurus vulgaris).
Four red squirrels (Sciurus vulgaris) were subjected to necropsy examination over a 3-year period as part of a broader surveillance study. The squirrels presented with cutaneous, subcutaneous and/or internal swellings and nodules that consisted microscopically of sheets of atypical round cells and multinucleated giant cells. There was moderate anisokaryosis with rare mitoses. Nuclei ranged from oval to indented or C-shaped and some were bizarre, twisted or multilobulated. Many giant cells also had a bizarre morphology, with anisokaryosis within individual cells. Giant cell nuclei were often multilobulated, ring-shaped or segmented. Affected internal organs varied depending on the squirrel, but included lymph node, kidney, intestinal tract and lungs. Representative lesions from each of the four squirrels were negative for acid-fast organisms. Formalin-fixed tissues from all four squirrels and ethanol-fixed tissue from one animal were negative for Mycobacterium by polymerase chain reaction. Immunohistochemically, the majority of mononuclear and multinucleated giant cells in all four squirrels strongly expressed vimentin and class II molecules of the major histocompatibility complex. Otherwise, the atypical mononuclear and multinucleated cells were negative for CD3, Pax-5, Mac387, CD18 and E-cadherin. Based on the combination of cellular morphology, arrangement and immunophenotype, a novel form of atypical histiocytosis is considered most likely in these squirrels, although the exact origin and triggering factors remain uncertain.


A new identity for misidentification syndromes.
The systematic study of delusional misidentification syndromes has been hampered by the often confusing and imprecise eponymic nomenclature currently in use. We present a case report that demonstrates the inadequacies of the current system. We then propose a new classification system designed to improve research and understanding in this important area.


How is the life without unicorns? A within-individual study on the relationship between uncertainty and mental health indicators: The moderating role of neuroticism.
The pandemic crisis of COVID-19 led to higher levels of uncertainty for individuals. Mental health has been outlined as a major key research priority to support and inform interventions. This study aimed to examine whether uncertainty influenced negative affect which in turn, resulted in worst levels of mental health, during the COVID-19 pandemic crisis, and test if neuroticism moderated the negative effect of uncertainty on mental health, via negative affect. To capture changes in daily uncertainty, negative affect and mental health, a daily design was adopted to test our model. We collected data through five consecutive days (N = 320), in the early "lockdown" stage of the pandemic. The multilevel results showed a significant mediation effect from daily uncertainty to daily mental health via daily negative affect. In addition, neuroticism moderated the mediated relationship, in such a way that the relationship between daily uncertainty on daily mental health, via daily negative affect was strengthened when neuroticism was higher. In sum, living without unicorns, or see the world though a black lens, is a factor that enhances the blackness of uncertainty.


Electrocuted to death: A case of an autoerotic fatality with body wrapping, anal masochism, and low abdomen mechanical stimulation.
Autoerotic paraphilic manipulations may be not only incredibly unusual but also hazardous and possibly fatal. Autoerotic experimenters sometimes combine several paraphilic mechanisms, both potentially lethal and non-lethal. A tragic outcome is usually a direct consequence of the life-threatening paraphilic mechanism(s); however, it may also result from an accidental complication arising from the constellation of the paraphilic realization. In this report, we present a case of an autoerotic death of a 30-year-old man who applied two potentially lethal paraphilic mechanisms-body wrapping and foreign body anal insertion-together with two other non-lethal paraphilic activities, autofetishism and transvestitism. However, the man's death ultimately occurred due to another associated autoerotic activity-stimulation of the lower abdomen with an electric massager, which accidentally short-circuited and caused fatal electrocution. Such autoerotic fatalities constitute a distinct subcategory of accidental autoerotic death.


Maturational age affects pirenperone dose-response pattern.
The effects of the 5-HT2 antagonist pirenperone on temperature preference were observed 1 hr after injection in mice aged 3, 5 and 7 days and at doses of 0.16, 0.48 and 1.6 mg/kg body weight. Although all 3 doses produced significant decreases in preferred temperature at 3 days, only the highest dose had significant effects at ages 5 and 7 days. Analysis of the data suggests that the dose-response relationship depends on age in a way that would be consistent with a shift in the dose-response curve with increasing age.


Back to the future: personal digital assistants in nursing education.
This article provides an overview of the current state of the art for incorporating personal digital assistants (PDAs) into nursing education. The development of PDA technology and the lessons learned by educators integrating PDA technology into nursing curricula are described. The current cycle of PDA evolution is discussed and contrasted with a proposed model for maximizing the impact of PDAs on technological innovation in nursing education and practice.


Transepiphyseal fracture of the femoral neck with dislocation of the femoral head and fracture of the posterior column of the acetabulum in a child.
We describe a 15-year-old boy with a posterior dislocation of the hip, fracture of the posterior column of the acetabulum and separation of the femoral capital epiphysis. To our knowledge no previous case in a child has been reported. Such high-energy injuries are extremely rare, and a poor outcome is expected. We advocate early referral to a specialised tertiary centre, and the use of a modification of Delbet's classification to reflect the complexity and displacement which may occur with this injury.


Patients' attitudes about the role of physicians in counseling about firearms.
This study investigated ambulatory clinic patients' perceptions regarding the physician's role in counseling about firearms in the United States. In all, 137 (94% response rate) patients completed a self-administered survey instrument during their office visit. Slightly more than half (56%) of the patients thought that physicians should talk to patients about guns in the home and 64% of the patients believed that doctors can affect public opinion about guns by counseling patients about gun-related dangers. One in five (21%) respondents reported that they, or a family member had been shot and 58% reported knowing someone personally who had been shot. Of the 23% who reported that someone in their home owned a gun, 52% indicated that the reason for owning a gun was for personal protection. Implications of the results for physician counseling are discussed.


Fine structural analysis of extraocular muscle spindles of a two-year-old human infant.
To clarify whether structural peculiarities formerly described in extraocular muscle (EOM) spindles of aged persons are already present in EOM spindles of a 2-year-old infant. Distal halves of two EOMs obtained from a 2-year-old multiorgan donor were immersion-fixed and prepared for electron microscopy. The fine structure of 10 muscle spindles and of 1 "false spindle" was investigated. Extraocular muscle spindles of an infant 2 years of age had 2- to 4-layered outer capsules, 376 microm (range, 217-606 microm) long and 97 microm (range, 55-140 microm) wide. In 10 EOM spindles, 4 to 16 intrafusal muscle fibers (mean, 7.9) were present. From a total of 79 intrafusal fibers, 43 (54%) were nuclear chain fibers, and 8 of the 43 exhibited posttraumatic degenerative changes. Thirty-six (46%) intrafusal fibers indistinguishable from extrafusal fibers were called anomalous fibers. No nuclear bag fibers were found. Each muscle spindle contained a variable number of chain fibers and at least one anomalous fiber. Sensory nerve terminals were restricted to the 35 normal chain fibers but were absent from damaged chain fibers and from anomalous fibers. One "false spindle" without a periaxial space was composed of three anomalous fibers and one chain fiber, all of them devoid of sensory terminals. Most structural particularities of human EOM spindles described in aged persons are already found in the infant. They cannot be interpreted as age-related changes, but rather they represent specific features of human EOM spindles.


Amino acid sequence of bovine white matter proteolipid.
The sequence of the bovine white matter proteolipid has been studied by a combination of proteolytic digestion and chemical cleavage at tryptophan residues. Alignment of peptides obtained by digestion with trypsin, chymotrypsin, clostripain, and Staphylococcus aureus protease gave the sequence of 52 residues at the amino terminus, 96 residues at the carboxyl terminus, and several additional segments. Peptides obtained by treatment of the protein with 2-(2-nitrophenylsulfenyl)-3-methyl-3'-bromoindolenine confirmed the alignment and extended the sequence. This information, combined with that of other investigators, permits us to propose the primary structure for the entire protein. On the basis of the sequence determination, the molecular weight of the proteolipid protein is 29,869.


The secret bread tests: selective primary health care or experimentation on human-beings?
This is a case history which describes an attempt to fortify the bread of Australian Aborigines in an isolated area of New South Wales. The medically successful intervention was accomplished by the publication of scientific enquiry and by attention to the culture of Aborigines. Paradoxically the long-term failure of the project was also due to the power of the written word and the neglect of the culture of the more densely populated and politically dominant white community. The need for doctors to be aware of the different approaches of primary health care and selective primary health care is stressed so that a general practitioner who provides health care for minority groups of the Fourth World can better define his role and relevance.


Neonates with culture proven sepsis have lower amounts and percentage of CD45RA+ T cells.
To evaluate the expression of lymphocyte subsets in newborns diagnosed as culture proven or culture negative sepsis and to investigate the differentiation. The aim of this study is to explore neonatal immunology in newborns diagnosed as culture proven or culture negative neonatal sepsis and to identify their place in the diagnosis. This prospective study was performed in newborns who were diagnosed as neonatal sepsis and hospitalized in a tertiary care hospital and who were classified as culture proven sepsis (n=12), as culture negative sepsis (n=21) and healthy (n=17). Lymphocyte subsets were obtained at time of diagnosis. Culture proven sepsis had statistically significant increase of WBC compared to culture negative sepsis and control groups (p<0.05). Significant decreases were observed of percentage of lymphocyte, when compared to culture negative sepsis and control group (p<0.05). Percentage of CD4(+) was lower in culture proven sepsis and absolute count of CD4(+) was lower in culture negative sepsis (p<0.05). Percentage and absolute count of CD45RA(+) were lower in culture negative sepsis than control and percentage of CD45RA(+) was lower in culture proven sepsis than control (p<0.05). Percentage of CD45RO(+) was higher in culture proven sepsis than control group (p<0.05). It is clear that during neonatal sepsis lymphocyte subsets are different from healthy controls. Whether the described abnormalities represent the absence of a normal maturation process, rather, pathological events is still not clear.


Subversion of immune responses by hepatitis C virus: immunomodulatory strategies beyond evasion?
Hepatitis C virus (HCV) is an important human pathogen that causes mild to severe liver disease worldwide. This positive-strand RNA virus is remarkably efficient at establishing persistent infection. In order for a non-cytopathic virus such as HCV to persist, the virus must escape immune recognition or inhibit the host immune responses. Immune escape via mutations in antigenic sites may occur under selective pressure during B-cell or T-cell responses to HCV infection, and may serve as a mechanism for the establishment HCV persistence. In addition to antigenic variation, HCV is able to subvert the host immune response by encoding specific viral gene product(s). An understanding of the mechanisms behind HCV persistence will provide a basis for the rational design of vaccines and novel therapeutic agents targeting human HCV infection.


[Substrate metabolism of muscles during the early postoperative period: the effect of glucose infusions].
Muscle substrate metabolism was studied by measuring arterial deep-venous substrate concentration differences across the forearm in metabolically healthy volunteers 3 h after abdominal surgery. Despite elevation of insulin levels following glucose infusion, no effect on muscular fractional extraction of glucose and no decrease of lactate and alanine production was found, whereas muscular lipolysis was inhibited to a normal extent and ketone utilization was reduced.


Everolimus does not further reduce polycystic liver volume when added to long acting octreotide: results from a randomized controlled trial.
Polycystic liver disease (PLD) is associated with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PCLD). The resulting hepatomegaly compromises quality of life. Somatostatin analogues reduce PLD volume by approximately 5% when given for 6-12 months. A pilot trial in 16 ADPKD patients demonstrated that sirolimus, an mTOR inhibitor, reduced PLD volume by 26%. The aim of this study was to assess the PLD volume reducing effect of everolimus and octreotide relative to octreotide monotherapy. We designed a randomized controlled trial that compared 48 weeks of everolimus 2.5 mg daily, combined with octreotide 40 mg intramuscularly every 4 weeks, to octreotide monotherapy. We included PCLD and ADPKD patients. Exclusion criteria were MDRD-GFR <60 ml/min/1.73 m(2) and liver volume <2500 ml. Primary outcome was change in liver volume measured with CT-volumetry. We randomized 44 PLD patients (29 PCLD, 15 ADPKD, 89% female) to treatment with octreotide (n=23) or octreotide-everolimus (n=21). Liver volume decreased by 3.5% (p<0.01) in the monotherapy arm, compared to 3.8% with combination therapy (p<0.01). The difference between treatment arms was not significant (p=0.73). Adding everolimus to octreotide in PLD does not increase the liver volume reducing effect of octreotide.


The first year of the COVID-19 pandemic and health among cancer survivors in the United States.
Cancer survivors represent a population with high health care needs. If and how cancer survivors were affected by the first year of the coronavirus disease 2019 (COVID-19) pandemic are largely unknown. Using data from the nationwide, population-based Behavioral Risk Factor Surveillance System (2017-2020), the authors investigated changes in health-related measures during the COVID-19 pandemic among cancer survivors and compared them with changes among adults without a cancer history in the United States. Sociodemographic and health-related measures such as insurance coverage, employment status, health behaviors, and health status were self-reported. Adjusted prevalence ratios of health-related measures in 2020 versus 2017-2019 were calculated with multivariable logistic regressions and stratified by age group (18-64 vs. ≥65 years). Among adults aged 18-64 years, the uninsured rate did not change significantly in 2020 despite increases in unemployment. The prevalence of unhealthy behaviors, such as insufficient sleep and smoking, decreased in 2020, and self-rated health improved, regardless of cancer history. Notably, declines in smoking were larger among cancer survivors than nonelderly adults without a cancer history. Few changes were observed for adults aged ≥65 years. Further research is needed to confirm the observed positive health behavior and health changes and to investigate the role of potential mechanisms, such as the national and regional policy responses to the pandemic regarding insurance coverage, unemployment benefits, and financial assistance. As polices related to the public health emergency expire, ongoing monitoring of longer term effects of the pandemic on cancer survivorship is warranted.


Long-term neuropsychological and psychosocial outcomes of decompressive hemicraniectomy following malignant middle cerebral artery infarctions.
This study examines long-term neuropsychological and psychosocial outcomes of survivors of malignant middle cerebral artery infarction treated via decompressive hemicraniectomy. A case series design facilitated a detailed analysis of the outcomes among five participants. Neuropsychological domains assessed included premorbid and current IQ, sustained, selective and divided attention, visual and auditory memory, executive functioning and visuo-spatial ability. Psychosocial domains assessed included self-rated depression, anxiety and quality of life. Participants and their main carer were asked about their retrospective view of surgery. All participants showed neuropsychological impairments in multiple cognitive domains, with preserved ability in others. Effects of laterality of brain function were evident in some domains. Clinically significant depression was evident in two participants. Overall quality of life was within average limits in three of four assessed participants. Four participants retrospectively considered surgery as having been a favourable course of action. While neuropsychological impairments are highly likely post-surgery, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life. Results do not support the suggestion that decompressive hemicraniectomy following malignant middle cerebral artery infarction necessarily leads to unacceptable neuropsychological or psychosocial outcomes. [ • Malignant middle cerebral artery infarction is a life threatening condition.• The neurosurgical procedure, "decompressive hemicraniectomy" has been shown to be life-saving among patients with this condition.• There is little known about the long-term neuropsychological and psychosocial outcomes following decompressive hemicraniectomy for malignant middle cerebral artery infarction.• This study concludes that neuropsychological impairments are highly probable post-surgery. However, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life.]


Factors affecting the target site uptake selectivity of estrogen radiopharmaceuticals: serum binding and endogenous estrogens.
The binding affinity of various substituted estrogens for human sex steroid binding protein (SBP) and rat alpha-fetoprotein (AFP) have been measured by hydroxylapatite adsorption (relative to estradiol = 100%). While 17 alpha-ethynyl and 11 beta-methoxy substituents reduce the affinity of estrogens for these serum binding proteins markedly, a 16 alpha-bromo or a 16 alpha-iodo substituent actually increases their affinity for AFP, though lowering it for SBP. As a consequence, the uterine uptake selectivity of 16 alpha [77Br]-bromoestradiol (relative affinity for AFP = 230%) and 16 alpha [125 I]-iodoestradiol (relative affinity for AFP = 180%) in young rats (day 19-23), when AFP levels are still substantial, is considerably less than in older animals (day 24-27). 11 beta-Methoxy-16 alpha [77Br]-bromoestradiol, which has lower affinity for AFP (5.1%), does not show this age-dependent uptake selectivity. In adult cycling female rats bearing dimethylbenz(a)anthracene(DMBA)-induced mammary tumors, there is a strong dependence of uterine and tumor uptake selectivity on the stage of the estrous cycle: uptake is maximal during diestrus and minimal during estrus. The effective use of estrogen radiopharmaceuticals as receptor-based imaging agents requires careful consideration of not only the binding affinity of the agent for the estrogen receptor, but also its interaction with non-receptor binding proteins. The modulation of receptor concentrations by endogenous ligands during endocrine cycles and physiological differences between animals will also affect markedly certain measures of the extent of receptor-mediated uptake by target sites.


Endoscopic approach of the overinfected urachal cyst.
The overinfected urachus cyst presents itself in quite different forms. In spite of the accuracy of ultrasound and abdominal CT scan, sometimes the diagnosis of this urachal abnormality is imprecise and even misleading. This article describes the transvesical endoscopic drainage of an infected urachal cyst with optimum result upon the treatment of this condition.


Chromosome reshuffling in birds of prey: the karyotype of the world's largest eagle (Harpy eagle, Harpia harpyja) compared to that of the chicken (Gallus gallus).
Like various other diurnal birds of prey, the world's largest eagle, the Harpy (Harpia harpyja), presents an atypical bird karyotype with 2n=58 chromosomes. There is little knowledge about the dramatic changes in the genomic reorganization of these species compared to other birds. Since recently, the chicken provides a "default map" for various birds including the first genomic DNA sequence of a bird species. Obviously, the gross division of the chicken genome into relatively gene-poor macrochromosomes and predominantly gene-rich microchromosomes has been conserved for more than 150 million years in most bird species. Here, we present classical features of the Harpy eagle karyotype but also chromosomal homologies between H. harpyja and the chicken by chromosome painting and comparison to the chicken genome map. We used two different sets of painting probes: (1) chicken chromosomes were divided into three size categories: (a) macrochromosomes 1-5 and Z, (b) medium-sized chromosomes 6-10, and (c) 19 microchromosomes; (2) combinatorially labeled chicken chromosome paints 1-6 and Z. Both probe sets were visualized on H. harpyja chromosomes by multicolor fluorescence in situ hybridization (FISH). Our data show how the organization into micro- and macrochromosomes has been lost in the Harpy eagle, seemingly without any preference or constraints.


Implantation and Establishment of Pregnancy in Human and Nonhuman Primates.
Implantation and the establishment of pregnancy are critical for the propagation of the species, but yet remain the limiting steps in human and primate reproduction. Successful implantation requires a competent blastocyst and a receptive endometrium during a specific window of time during the menstrual cycle to initiate the bilateral communication required for the establishment of a successful pregnancy. This chapter provides an overview of these processes and discusses the molecular mechanisms associated with implantation of the blastocyst and decidualization of the uterus in primates.


Immediate effects of a new microprocessor-controlled prosthetic knee joint: a comparative biomechanical evaluation.
To investigate the immediate biomechanical effects after transition to a new microprocessor-controlled prosthetic knee joint. Intervention cross-over study with repeated measures. Only prosthetic knee joints were changed. Motion analysis laboratory. Men (N=11; mean age ± SD, 36.7±10.2y; Medicare functional classification level, 3-4) with unilateral transfemoral amputation. Two microprocessor-controlled prosthetic knee joints: C-Leg and a new prosthetic knee joint, Genium. Static prosthetic alignment, time-distance parameters, kinematic and kinetic parameters, and center of pressure. After a half-day training and an additional half-day accommodation, improved biomechanical outcomes were demonstrated by the Genium: lower ground reaction forces at weight acceptance during level walking at various velocities, increased swing phase flexion angles during walking on a ramp, and level walking with small steps. Maximum knee flexion angle during swing phase at various velocities was nearly equal for Genium. Step-over-step stair ascent with the Genium knee was more physiologic as demonstrated by a more equal load distribution between the prosthetic and contralateral sides and a more natural gait pattern. When descending stairs and ramps, knee flexion moments with the Genium tended to increase. During quiet stance on a decline, subjects using Genium accepted higher loading of the prosthetic side knee joint, thus reducing same side hip joint loading as well as postural sway. In comparision to the C-Leg, the Genium demonstrated immediate biomechanical advantages during various daily ambulatory activities, which may lead to an increase in range and diversity of activity of people with above-knee amputations. Results showed that use of the Genium facilitated more natural gait biomechanics and load distribution throughout the affected and sound musculoskeletal structure. This was observed during quiet stance on a decline, walking on level ground, and walking up and down ramps and stairs.


Spontaneous isolated posterior communicating artery dissection in a young adult with hyperhomocysteinemia.
A 28-year-old man presented with an acute spontaneous dissection of the left posterior communicating artery with associated ipsilateral thalamic and internal capsular infarctions. Positive risk factors included smoking and family history of ischemic heart disease. He was also found to have hyperhomocysteinemia, which has been implicated as a risk factor for spontaneous cervical artery dissection, but to date, no association has been shown with spontaneous intracranial arterial dissection.


[Surgical intervention of hepatocellular carcinoma with bile duct thrombi].
To summarize the experience of surgical intervention for hepatocellular carcinoma (HCC) with bile duct thrombi (BDT), and to evaluate the influence on prognosis. From 1994 to 2002, 15 patients with HCC and BDT who underwent surgical intervention were retrospectively analyzed. The operative procedures included hepatectomy with removal of BDT (n = 7), hepatectomy combined with extrahepatic bile duct resection (n = 4), thrombectomy through choledochotomy (n = 3), and piggy-back orthotopic liver transplantation (n = 1). The 1- and 3-year survival rates were 73.3% and 40%, respectively. Two patients survived over 5 year. The survival rate of patients with portal vein invasion was significantly lower than that of patients without portal vein invasion (P < 0.05). Surgical intervention was effective for patients with HCC and BDT. Operation after recurrence can prolong the survival time. Liver transplantation is a new operative procedure worthy of study.


A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome.
Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27-89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) <1 year (N=28, 25%); group 2: relapsed/refractory AML with CRD ⩾1 year (N=5, 5%); group 3: untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome (MDS) or untreated myelofibrosis (MF; N=57, 52%); and group 4: AML evolving from MDS or relapsed/refractory MDS or MF (N=20, 18%). Treatment consisted of decitabine 20 mg/m(2) daily for 5 days and GO 3 mg/m(2) on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years.


Post-traumatic hydrocephalus in patients with severe head injury.
Computerized tomography was performed on 100 consecutive patients suffering from severe head injury, on admission, after 3, 5, 14, and 90 days and 1 year. Ventricular enlargement was evaluated in the surviving patients based upon serial CT examinations. The presence or absence of ventricular enlargement was correlated with the clinical outcome. The study indicates that a significant correlation does exist between the outcome and ventricular size. Hydrocephalus was seen in only four out of the 29 patients who developed ventriculomegaly.


Ventricular histamine concentrations and mast cell counts in the rat heart during acute ischaemia.
The ventricular histamine concentrations and mast cell counts of naive and disodium cromoglycate-treated rats subjected to acute left coronary artery ligation under pentobarbitone anaesthesia were examined. In naive animals, there was a significant increase in the right ventricular histamine level at 2 min following left coronary artery ligation. Left ventricular histamine concentrations tended to decrease, and were significantly lower than those of the right ventricle at 5 min. However there were no significant changes in mast cell counts of the right or left ventricles after left coronary artery ligation. Treatment with disodium cromoglycate did not significantly alter the ventricular mast cell counts, interfere with the changes in ventricular histamine concentrations, or the occurrence of early ventricular arrhythmias and haemodynamic changes in response to acute left coronary artery ligation. It is suggested that the increase in the right and decrease in the left ventricular histamine concentrations during acute myocardial ischaemia involves mainly the non-mast cell stores, instead of mast cell sources, of cardiac histamine.


Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection.
Faecal microbiota transplant (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect C. difficile germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT's efficacy in treating the condition. Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of bsh/baiCD genes involved in bile metabolism. Human data were validated in C. difficile batch cultures and a C57BL/6 mouse model of rCDI. From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent C. difficile germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and bsh/baiCD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered bsh-expressing E. coli and naturally BSH-producing organisms (Bacteroides ovatus, Collinsella aerofaciens, Bacteroides vulgatus and Blautia obeum) reduced TCA-mediated C. difficile germination relative to culture supernatant of wild-type (BSH-negative) E. coli. C. difficile total viable counts were ~70% reduced in an rCDI mouse model after administration of E. coli expressing highly active BSH relative to mice administered BSH-negative E. coli (p<0.05). Restoration of gut BSH functionality contributes to the efficacy of FMT in treating rCDI.


The follicle promotes the evolution of variants of avian leukosis virus subgroup J in vertical transmission.
Avian leukosis virus (ALV) is one of the main causative agent of tumor development, which brings enormous economic losses to the poultry industry worldwide. ALV can be transmitted horizontally and vertically, and the latter often give rise to more adverse pathogenicity. However, the propagation and evolution of ALV underlying vertical transmission remain not-well understood. Herein, an animal model for the evolution of variants of ALV subgroup J (ALV-J) in the vertical transmission was built and different organs from infected hens and plasma from their ALV-positive progenies were collected, and then three segments in the hypervariable regions of ALV (gp85-A, gp85-B, LTR-C) were amplified and sequenced using conventional Sanger sequencing and MiSeq high-throughput sequencing, respectively. The results showed that the genomic diversity of ALV-J occurred in different organs from ALV-J infected hen, and that the dominant variants in different organs of parental hens, especially in follicle, changed significantly compared with original inoculum strain. Notably, the dominant variants in progenies exhibited higher homologies with variants in parental hens' follicle (88.9%-98.9%) than other organs (85.6%-91.1%), and most consistent mutations in the variants were observed between the progenies and parental hen's follicle. Furthermore, HyPhy analysis indicated that the global selection pressure value (ω) in the follicle is significantly higher than those in other organs. In summary, an animal model for vertical transmission was built and our findings revealed the evolution of variants of ALV in the process of vertical transmission, moreover, the variants were most likely to be taken to the next generation via follicle, which may be related to the higher selection pressure follicle underwent.


Evolution of natural populations in the Drosophila melanogaster sigma virus system I. Languedoc (southern France).
In natural populations of Drosophila melanogaster, sigma virus is usually present in a minority of individuals. The virus is transmitted transovarially but is not contagious from fly to fly. Two viral Types (I and II) are found in populations. One of them (Type II) is better adapted to an allele for resistance to the virus, present as a polymorphism in fly populations. Previous observations have led to the hypothesis that a viral Type II originating in central France might be invading populations. The study of Languedoc populations was undertaken to examine this hypothesis. Two striking phenomena were observed. The strong increase in Type II clones frequency (from 0.53 to 0.91) confirmed that there was invasion in this region. The frequency of infected flies also increased dramatically, at levels never observed elsewhere yet, which indicates that Languedoc should present some unusual characteristics. The epidemiological consequences of such a burst, in the case of a pathogenic virus would have to be taken into consideration. Significant changes in other viral characteristics, from 1983 to 1987, in Languedoc populations have also been documented.


Exosomal circDNER enhances paclitaxel resistance and tumorigenicity of lung cancer via targeting miR-139-5p/ITGB8.
Circular RNAs (circRNAs) are regarded as vital regulatory factors in various cancers. However, the biological functions of circDNER in the paclitaxel (PTX) resistance of lung cancer remain largely unexplored. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze circDNER, miR-139-5p, and ITGB8. Cell proliferation was assessed via colony formation and MTT assays. Cell apoptosis was evaluated by flow cytometry. Western blot was performed to assess protein expression. The targeted interaction among circDNER, miR-139-5p, and ITGB8 were validated using dual-luciferase reporter or RNA immunoprecipitation assays. Inhibition of circDNER reduced IC50 of PTX, inhibited cell proliferation, invasion and migration, as well as promoted cell apoptosis in PTX-resistant lung cancer cells. Mechanistically, circDNER sponged miR-139-5p to upregulate ITGB8 expression. Overexpression of miR-139-5p reversed the biological functions mediated by circDNER in PTX-resistant lung cancer cells. MiR-139-5p overexpression suppressed PTX resistance and malignant behaviors of PTX-resistant lung cancer cells, with ITGB8 elevation rescued the impacts. Moreover, we demonstrated that circDNER was upregulated in plasma exosomes from lung cancer patients. The plasma exosomes derived from these patients are the key factors enhancing the migration and invasion potential of lung cancer cells. The circDNER mediated miR-139-5p/ITGB8 axis suppresses lung cancer progression. Our findings suggest that circDNER might act as a potential prognostic biomarker and therapeutic target for lung cancer treatment.


Pointing Disrupts Preschoolers' Ability to Discriminate Between Knowledgeable and Ignorant Informants.
By 4 years of age, children have been reinforced repeatedly for searching where they see someone point. In two studies, we asked whether this history of reinforcement could interfere with young children's ability to discriminate between a knowledgeable and an ignorant informant. Children watched as one informant hid a sticker while another turned around, and then both informants indicated where they though the sticker was, either by pointing or by using a less practiced means of reference. Children failed to discriminate between the two informants when they pointed, but they chose the location indicated by the knowledgeable informant when the informants used a cue other than pointing. Pointing can disrupt as basic an understanding as the link between seeing and knowing.


Modelling climate variabilities and global rice production: A panel regression and time series analysis.
Climate change threatens agriculture and it remains a present global challenge to food security and Sustainable Development Goals. The potential impact on the supply of crops such as rice is seen as a major food security issue that requires intervention on several fronts. The literature on rice production, climate variations and climate change show several studies outlining various impacts on rice supply as a result of variations in temperature and rainfall. This study intends to further explore the impacts on rice production caused by temperature changes and rainfall variation by analyzing and modelling the production of rice by the top rice-producing countries globally. A time series of the national rice production and yield along with national average annual temperature and rainfall were sourced for 15 major rice-producing countries. The trends of the time series were then compared between the rice productivity variables and temperature and rainfall. A panel regression model was also developed to further assess the relationship between rice production and temperature and rainfall. The time series showed that rice production and yield are increasing for the majority of the countries analyzed. The panel regression model however showed that continued increase in temperature can result in decreased production of rice and that rainfall volume directly impacts rice output and therefore shows rice production is highly susceptible to flooding and drought events caused by climate variabilities.


Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection.
To track epitope-specific CD4(+) T cells at a single-cell level during influenza infection, the MHC class II-restricted OVA(323-339) epitope was engineered into the neuraminidase stalk of influenza/A/WSN, creating a surrogate viral antigen. The recombinant virus, influenza A/WSN/OVA(II), replicated well, was cleared normally, and stimulated both wild-type and DO11.10 or OT-II TCR transgenic OVA-specific CD4(+) T cells. OVA-specific CD4 T cells proliferated during infection only when the OVA epitope was present. However, previously primed (but not naive) transgenic CD4(+) T cells were recruited to the infected lung both in the presence and absence of the OVA(323-339) epitope. These data show that, when primed, CD4(+) T cells may traffic to the lung in the absence of antigen, but do not proliferate. These results also document a useful tool for the study of CD4 T cells in influenza infection.


Alpha 2 adrenergic receptors on GABAergic, putative sleep-promoting basal forebrain neurons.
The basal forebrain plays an important role in the modulation of cortical activity and sleep-wake states. Yet its role must be multivalent as lesions reportedly diminish cortical fast activity and also cortical slow activity along with slow wave sleep (SWS). Basal forebrain cholinergic vs. GABAergic cell groups could differentially influence these processes. By labelling recorded neurons with Neurobiotin (Nb) using the juxtacellular technique and identifying them by immunostaining, we previously found that whereas all cholinergic cells increased their firing, the majority of GABAergic neurons decreased their firing in association with evoked cortical activation in urethane-anaesthetized rats. Here, we examined the possibility that such GABAergic, cortical activation 'off' cells might bear alpha 2 adrenergic receptors (alpha2AR) through which noradrenaline (NA) could inhibit them during cortical activation. First using simple dual-immunostaining for glutamic acid decarboxylase (GAD) and the alpha2AAR, we found that the majority (approximately 60%) of GAD-immunopositive (GAD+) neurons through the magnocellular preoptic nucleus (MCPO) and substantia innominata (SI) were labelled for the alpha2AAR. Second, in urethane-anaesthetized rats, we examined whether Nb-labelled, GAD+ cortical activation 'off' neurons that discharged maximally in association with cortical slow wave activity, were immunopositive for alpha2AAR. We found that all the Nb+/GAD+'off' cells were labelled for the alpha2AAR. Such cells could be inhibited in association with cortical activation and waking when noradrenergic locus coeruleus (LC) neurons discharge and be disinhibited with cortical slow waves and SWS when these neurons become inactive. We thus propose that alpha2AR-bearing GABAergic basal forebrain neurons constitute sleep-active and sleep-promoting neurons.


Simultaneous mass spectrometric measurement of prostaglandins E1 (PGE1) and PGE2 with a deuterated internal standard.
The use of (3,3,4,4-2H4)PGE2 as internal standard for the quantitative measurement of PGE1 by gas chromatography-mass spectrometry is reported. A method for the simultaneous analysis of PGE1 and PGE2 is also described. The prostaglandins were analyzed by selected ion monitoring as the methyl ester-trimethylsilyl ether (ME-TMS) derivatives of PGB1 and PGB2, respectively. In all cases, a linear response over the range 1 to 70 ng (2.8 to 198 pmoles) was demonstrated. The use of this procedure is exemplified by its application to the PG analysis of sheep seminal vesicles.


Roles of NG2-glia in ischemic stroke.
Recent studies have shown that a widely distributed class of glial cells, termed NG2-glia, engages in rapid signaling with surrounding neurons through direct synaptic contacts in the developing and mature central nervous system (CNS). This unique glial cell group has a typical function of proliferating and differentiating into oligodendrocytes during early development of the brain, which is crucial to axon myelin formation. Therefore, NG2-glia are also called oligodendrocyte precursor cells (OPCs). In vitro and in vivo studies reveal that NG2-glia expressing receptors and ion channels demonstrate functional significance for rapid signaling with neuronal synapses and modulation of neuronal activities in both physiological and pathological conditions. Although it is well known that NG2-glia play an important role in demyelinating diseases such as multiple sclerosis, little is known about how NG2-glia or OPCs impact neurons and brain function following ischemic injury. This review summarizes recent progress on the roles of NG2-glia in ischemic stroke and illustrates new approaches for targeting NG2-glia in the brain to treat this disease.


Compact Feeding Network for Array Radiations of Spoof Surface Plasmon Polaritons.
We propose a splitter feeding network for array radiations of spoof surface plasmon polaritons (SPPs), which are guided by ultrathin corrugated metallic strips. Based on the coupled mode theory, SPP fields along a single waveguide in a certain frequency range can be readily coupled into two adjacent branch waveguides with the same propagation constants. We propose to load U-shaped particles anti-symmetrically at the ends of such two branch waveguides, showing a high integration degree of the feeding network. By controlling linear phase modulations produced by the U-shaped particle chain, we demonstrate theoretically and experimentally that the SPP fields based on bound modes can be efficiently radiated to far fields in broadside direction. The proposed method shows that the symmetry of electromagnetic field modes can be exploited to the SPP transmission network, providing potential solutions to compact power dividers and combiners for microwave and optical devices and systems.