Cell Division Cycle 5-Like Regulates Metaphase-to-Anaphase Transition in Meiotic Oocyte.
The quality of oocytes is a vital factor for embryo development. Meiotic progression through metaphase I usually takes a relatively long time to ensure correct chromosome separation, a process that is critical for determining oocyte quality. Here, we report that cell division cycle 5-like (Cdc5L) plays a critical role in regulating metaphase-to-anaphase I transition during mouse oocyte meiotic maturation. Knockdown of Cdc5L by small interfering RNA injection did not affect spindle assembly but caused metaphase I arrest and subsequent reduced first polar body extrusion due to insufficient anaphase-promoting complex/cyclosome activity. We further showed that Cdc5L could also directly interact with securin, and Cdc5L knockdown led to a continuous high expression level of securin, causing severely compromised meiotic progression. The metaphase-to-anaphase I arrest caused by Cdc5L knockdown could be rescued by knockdown of endogenous securin. In summary, we reveal a novel role for Cdc5L in regulating mouse oocyte meiotic progression by interacting with securin.


A quantitative proteomic approach of the different stages of colorectal cancer establishes OLFM4 as a new nonmetastatic tumor marker.
Expression profiles represent new molecular tools that are useful to characterize the successive steps of tumor progression and the prediction of recurrence or chemotherapy response. In this study, we have used quantitative proteomic analysis to compare different stages of colorectal cancer. A combination of laser microdissection, OFFGEL separation, iTRAQ labeling, and MALDI-TOF/TOF MS was used to explore the proteome of 28 colorectal cancer tissues. Two software packages were used for identification and quantification of differentially expressed proteins: Protein Pilot and iQuantitator. Based on ∼1,190,702 MS/MS spectra, a total of 3138 proteins were identified, which represents the largest database of colorectal cancer realized to date and demonstrates the value of our quantitative proteomic approach. In this way, individual protein expression and variation have been identified for each patient and for each colorectal dysplasia and cancer stage (stages I-IV). A total of 555 proteins presenting a significant fold change were quantified in the different stages, and this differential expression correlated with immunohistochemistry results reported in the Human Protein Atlas database. To identify a candidate biomarker of the early stages of colorectal cancer, we focused our study on secreted proteins. In this way, we identified olfactomedin-4, which was overexpressed in adenomas and in early stages of colorectal tumors. This early stage overexpression was confirmed by immunohistochemistry in 126 paraffin-embedded tissues. Our results also indicate that OLFM4 is regulated by the Ras-NF-κB2 pathway, one of the main oncogenic pathways deregulated in colorectal tumors.


Anaerobic degradation of 2-fluorobenzoate by benzoate-degrading, denitrifying bacteria.
Three strains of anaerobically benzoate-degrading, denitrifying bacteria of the genus Pseudomonas were able to grow on 2-fluorobenzoate as the sole carbon and energy source. Fluoride ion release was stoichiometric, and the reduction of dissolved organic carbon indicated total degradation. Cells grown anaerobically with benzoate were adapted for immediate growth with 2-fluorobenzoate, and both compounds were substrates for an inducible benzoyl-coenzyme A synthetase, the initial enzyme of anaerobic degradation. It is proposed that fluoride is eliminated gratuitously by a regioselective reaction in a sequence common to both carbon sources. Benzoate, but not 2-fluorobenzoate, was oxidized by aerobically grown cells.


A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients.
We have studied the clinical presentation and course of a chronic inflammatory disease occurring in childhood and observed in 30 patients. The first symptoms were generally present at birth, except in a few patients where they were first noticed in early infancy. All the patients had the association of three main symptoms: neurological, cutaneous and articular. The skin rash was the first symptom observed in all the patients and looked like a chronic non pruritic urticaria varying during the day. The articular manifestations involved knees, ankles and feet, elbows, wrists and hands unaffecting the other joints. They could be mild giving arthritis during flare-ups or severe with major radiological modifications affecting the epiphysis, metaphysis and growth cartilage. The neurological manifestations were characterized by a chronic meningitis and symptoms indicating meningeal irritation: headaches, seizures, spasticity of legs. Most patients had a cerebral atrophy and a low IQ. Sensory organ involvement occurred progressively during the follow-up: ocular inflammation with optic atrophy, deafness and hoarseness. Common morphological features characterized these patients with short stature, head enlargement, saddle back nose and short and thick extremities with clubbing of fingers. The course was that of a chronic inflammatory disease with numerous flare-ups associating fever, splenomegaly and adenomegaly. Except for a high level of eosinophils in blood, CSF and tissues, the biology was non specific and only exhibited features of inflammation. Except for two families, the disease was sporadic. A high frequency of prematurity with features resembling a foetal infection was observed but no proof of a possible causal virus has so far been found so that etiology remains unknown.


The Histone Acetyltransferase MOF Regulates SIRT1 Expression to Suppress Renal Cell Carcinoma Progression.
Renal cell carcinoma (RCC) is one of the most common and lethal human urological malignancies around the world. Although many advancements in diagnostic and therapeutic strategies have been acquired, the prognosis of patients with metastatic RCC was poor. Thus, there is an urgent need to understand the molecular mechanism of RCC. The quantitative real-time PCR (qRT-PCR) was used to detect the RNA expression of MOF in human RCC tissues and cell lines. The protein expression of MOF was analyzed with immunohistochemistry (IHC) and Western blot. To understand the regulatory mechanism of MOF in liver cancer, ChIP-qPCR assay and dual-luciferase assay were performed. Moreover, a series of in vivo and in vitro experiments were conducted to evaluate the effect of MOF on renal cell carcinoma progression. In the present study, we found that Males absent on the first (MOF), a histone acetyltransferase involved in transcription activation, was significantly decreased in both RCC tissues and RCC cells compared to normal tissues and non-cancer cells. Moreover, MOF downregulation was associated with advanced histological grade, pathologic stage and distant metastasis of RCC patients. Ectopic expression of MOF could significantly attenuate cell proliferation and promote cell apoptosis. Besides, MOF overexpression also suppressed migration of RCC cells through inhibiting epithelial-mesenchymal transition (EMT). Importantly, the inhibition of tumor growth by MOF was further confirmed by in vivo studies. Mechanism dissection revealed that MOF could transcriptionally upregulate the expression of SIRT1, leading to attenuated STAT3 signaling, which was involved in cell proliferation and migration. Moreover, SIRT1 knockdown could restore the biological function induced by MOF overexpression. Our findings indicated that MOF serves as a tumor suppressor via regulation of SIRT1 in the development and progression of RCC, and MOF might be a potent biomarker for diagnosis and prognosis prediction of RCC patients.


Saccular Thoracoabdominal Aneurysms in Systemic Lupus Erythematosus.
Aortic aneurysm is a rare but a serious complication of systemic lupus erythematosus. We report the case of a 59-year-old man with systemic lupus erythematosus disease who presented with symptomatic saccular thoracoabdominal aneurysms. The 2 aneurysms were resected and 2 silver-coated tube grafts were interposed. Surgical pathology revealed lymphoplasmacytic aortitis, without pathogenic agents. This is the first case of a double localization of saccular thoracoabdominal aneurysms with inflammatory aortitis caused by lupus. In patients with a history of systemic lupus erythematosus, with or without active inflammation, screening for aortic disease should be selectively performed if other risk factors for aortic aneurysm are present.


Opioidergic control of gonadotrophin secretion in the prepubertal gilt during restricted feeding and realimentation.
Prepubertal gilts, having undergone a 7-day period of feed restriction to a maintenance ration, were allocated to one of 4 treatments; restricted feeding at 09:00 and 17:00 h for an 8th day both with (Group RN) and without (Group R) administration of the opioid antagonist naloxone hydrochloride (1 mg.kg-1 at 09:30 h followed by 0.5 mg.kg-1 at hourly intervals for 7 h), or feed to appetite with (Group ALN) and without (Group AL) naloxone administration. Gilts were bled at 10-min intervals on Day 8 from morning to evening feed and plasma LH, FSH and prolactin concentrations were measured by radioimmunoassay. Compared with Group R gilts, Group AL gilts exhibited significantly (P less than or equal to 0.05) higher mean and maximum LH concentrations and pulsatility, lower prolactin concentrations (P less than 0.05) but no significant difference in FSH secretion. Naloxone significantly depressed the increase in LH after re-feeding (Group ALN) (P less than 0.05). Once again there were no significant effects on FSH secretion. Naloxone also significantly depressed prolactin secretion in feed-restricted gilts (P less than 0.05). These results confirm that re-feeding of feed-restricted prepubertal gilts stimulates an immediate increase in LH secretion and that this elevation is not mediated via a suppression of inhibitory endogenous opioidergic tone. Rather, naloxone treatment appeared to expose a latent inhibition of LH secretion. The control of LH secretion is distinct from that of FSH in this model.


Bidirectional transfer and tissue accumulation of folic acid by rat intestine in vitro.
The transfer and tissue content of 3H-pteroylmonoglutamate (PteGlu) from the mucosal to the serosal side (Jms, TCm) and in the reverse direction (Jsm, TCs) was studied using the everted sac technique. In the entire intestine, except for the colon, 3H-PteGlu was transferred preferentially into the serosal solution. When 3H-PteGlu was applied to the serosal side the final tissue concentration in either jejunal, duodenal, ileal or colonic segments was not significantly different from each other and about two-fold the serosal concentration. Apparently there exists a specific transfer process from the mucosal to the serosal side in the jejunum. The transfer of 3H-PteGlu shows saturation kinetics (S0.5 = 4.9 X 10(-5) mol/l). At low concentration (2 nmol/l) 3H-PteGlu was accumulated within the mucosal epithelium (tissue/mucosal fluid ratio = 3.8). Transfer and accumulation in the mucosal tissue of 3H-PteGlu apparently need high activation energy as indicated by the temperature dependency of these processes. Finally, transfer and accumulation in the tissue of 3H-PteGlu could be inhibited by salazosulfapyridine and phenobarbital.


Anatomical Studies of the Orbital Cavity Using Three-Dimensional Computed Tomography.
This study was designed to analyze the morphometric characteristics of the orbital cavity using three-dimensional computed tomography in Asians. Two hundred seventy-six orbits in 142 Asians (74 men and 68 women) were examined and compared according to age, sex, and laterality (right and left). Mean orbital morphometric values were as follows. Orbital cavity depth was 49.60 mm from optic foramen to orbitale (inferior) and 41.32 mm from optic foramen to lacrimal crest (medial). Anterior and posterior orbital medial wall heights were 17.73 and 12.76 mm, respectively. Medial, middle, and lateral orbital floor lengths were 39.08, 29.56, and 20.08 mm, respectively. Anterior and posterior orbital floor width was 21.87 and 12.00 mm, respectively. For the orbital inferior-medial angle, anterior, middle, and posterior value was 132.11°, 126.24°, and 136.88°, respectively. Inferior orbital cavity depth, anterior orbital medial wall height, and orbital floor length tended to increase with aging, whereas orbital floor width tended to decrease with aging. No significant differences were found in terms of laterality, and values were greater in men than in women. This quantitative analysis of orbital measurements will allow surgeons to plan operations more accurately and will help predict outcomes.


Medicare program; criteria and standards for evaluating intermediary and carrier performance during fiscal year 1988--HCFA. General notice with comment period.
This notice describes the criteria and standards to be used for evaluating the performance of fiscal intermediaries and carriers in the administration of the Medicare program for the fiscal year beginning October 1, 1987. The results of these evaluations are considered whenever we enter into, renew, or terminate an intermediary or carrier contract or take other contract actions; assign or reassign providers of services to an intermediary; or designate regional or national intermediaries. In addition, this notice describes the methodology used for identifying contractors for competitive replacement under section 2326 of the Deficit Reduction Act of 1984.


Selective beta 1-receptor full agonists, T-0509 and T-1583, increase the force monophasically and cyclic AMP biphasically in canine ventricular muscle.
In canine right ventricular muscle, we investigated the mechanism of action of the positive inotropic effects of T-0509 and T-1583, derivatives of denopamine, a new selective beta 1-partial agonist. T-1583 has already been characterized as a selective beta 1 full agonist (pD2 = 7.39). T-0509 also behaved as a full agonist (pD2 = 8.27) and its positive inotropic effect was antagonized competitively by atenolol (pA2 = 7.53) and noncompetitively by carbachol, and potentiated by 3-isobutyl-1-methylxanthine. With increasing concentrations of T-0509 (10(-9) to 10(-7) M) and T-1583 (10(-8) to 10(-6) M), cyclic AMP increased and increases reached plateaus approximately 40% above the baseline levels with approximately 10(-7) M T-0509 and approximately 10(-6) M T-1583, at which their positive inotropic effects reached maxima. However, with further increasing concentrations, cyclic AMP again started to increase and increases amounted to approximately 120% above the baseline levels with 10(-5) M T-0509 and with 10(-4) M T-1583. These results suggest the following: Like denopamine, the selective beta 1 full agonists, T-0509 and T-1583, at lower concentrations produce positive inotropic effects accompanied by only a small increase in cyclic AMP via stimulation of high-affinity beta 1-receptors. In higher concentrations, unlike denopamine, the two full agonists produce large increases in cyclic AMP loosely coupled to positive inotropy via stimulation of low-affinity beta 1-receptors.


Vibrio Pathogens: A Public Health Concern in Rural Water Resources in Sub-Saharan Africa.
Members of the Vibrio genus are autochthonous inhabitants of aquatic environments and play vital roles in sustaining the aquatic milieu. The genus comprises about 100 species, which are mostly of marine or freshwater origin, and their classification is frequently updated due to the continuous discovery of novel species. The main route of transmission of Vibrio pathogens to man is through drinking of contaminated water and consumption inadequately cooked aquatic food products. In sub-Saharan Africa and much of the developing world, some rural dwellers use freshwater resources such as rivers for domestic activities, bathing, and cultural and religious purposes. This review describes the impact of inadequately treated sewage effluents on the receiving freshwater resources and the associated risk to the rural dwellers that depends on the water. Vibrio infections remain a threat to public health. In the last decade, Vibrio disease outbreaks have created alertness on the personal, economic, and public health uncertainties associated with the impact of contaminated water in the aquatic environment of sub-Saharan Africa. In this review, we carried out an overview of Vibrio pathogens in rural water resources in Sub-Saharan Africa and the implication of Vibrio pathogens on public health. Continuous monitoring of Vibrio pathogens among environmental freshwater and treated effluents is expected to help reduce the risk associated with the early detection of sources of infection, and also aid our understanding of the natural ecology and evolution of Vibrio pathogens.


Inhibition of organic cation transporter 3 activity by tyrosine kinase inhibitors.
Organic cation transporter (OCT) 3 (SLC22A3) is a widely expressed drug transporter, handling notably metformin and platinum derivatives, as well as endogenous compounds like monoamine neurotransmitters. OCT3 has been shown to be inhibited by a few marketed tyrosine kinase inhibitors (TKIs). The present study was designed to determine whether additional TKIs may interact with OCT3. For this purpose, the effects of 25 TKIs toward OCT3 activity were analyzed using OCT3-overexpressing HEK293 cells. 13/25 TKIs, each used at 10 µM, were found to behave as moderate or strong inhibitors of OCT3 activity, that is, they decreased OCT3-mediated uptake of the fluorescent dye 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide by at least 50% or 80%, respectively. This OCT3 inhibition was correlated to some molecular descriptors of TKIs, such as the percentage of H atoms and that of cationic forms at pH = 7.4. It was concentration-dependent, notably for brigatinib, ceritinib, and crizotinib, which exhibited low half maximal inhibitory concentration (IC50 ) values in the 28-106 nM range. Clinical concentrations of these three marketed TKIs, as well as those of pacritinib, were next predicted to inhibit in vivo OCT3 activity according to regulatory criteria. Cellular TKI accumulation experiments as well as trans-stimulation assays, however, demonstrated that OCT3 does not transport brigatinib, ceritinib, crizotinib, and pacritinib, thus discarding any implication of OCT3 in the pharmacokinetics of these TKIs. Taken together, these data suggest that some TKIs may act as potent inhibitors of OCT3 activity, which may have consequences in terms of drug-drug interactions and toxicity.


Bats as the main prey of wintering long-eared owl (Asio otus) in Beijing: Integrating biodiversity protection and urban management.
The loss of biodiversity from urbanized areas is a major environmental problem challenging policy-makers throughout the world. Solutions to this problem are urgently required in China. We carried out a case study of wintering long-eared owls (Asio otus) and their main prey to illustrate the negative effects of urbanization combined with ineffective conservation of biodiversity in Beijing. Field monitoring of owl numbers at two roosting sites from 2004 to 2012 showed that the owl population had fallen rapidly in metropolitan Beijing. Analysis of pellet contents identified only seven individuals of two species of shrew. The majority of mammalian prey comprised four bat and seven rodent species, making up 29.3% and 29.5% of the prey items, respectively. Prey composition varied significantly among years at the two sample sites. At the urban site the consumption of bats and rodents declined gradually over time, while predation on birds increased. In contrast, at the suburban site the prey composition showed an overall decrease in the number of bats, a sharp increase and a subsequent decrease in bird prey, and the number of rodent prey fell to a low point. Rapid development of real estate and inadequate greenfield management in city parks resulted in negative effects on the bird and small mammal habitat of urban areas in Beijing. We suggest that measures to conserve biodiversity should be integrated into future urban planning to maintain China's rich biodiversity while also achieving sustainable economic development.


Designing Ruby: Protocol for a 2-Arm, Brief, Digital Randomized Controlled Trial for Internalized Weight Bias.
Weight bias internalization, also known as weight self-stigma, is a serious health concern for individuals with higher body weight. Weight bias internalization is associated with the greater avoidance of health care and health-promoting activities, disordered eating, social isolation, and weight gain. Elevated weight bias internalization has been associated with low self-compassion, yet few investigations have explored self-compassion as a potential mechanism for reducing internalized weight bias. Ruby is a 2-arm randomized controlled trial that was designed to test the efficacy of a 4-week digital self-compassion intervention to reduce internalized weight bias compared with a wait-list control. Adults with elevated internalized weight bias and a BMI of >30 kg/m2 (N=80) were recruited. Ruby is a standalone digital trial that will be delivered entirely via a smartphone and will involve web-based data collection and text messages. The intervention content will include psychoeducation and daily mindfulness practices with a focus on self-compassion and body concerns. We will use intent-to-treat analyses to examine changes in weight bias internalization throughout time by treatment arm. The analyses will be conducted by using one-way analysis of covariance models and linear mixed models. The protocol was designed in May 2020 and approved in December 2020. Data collection is currently underway. Ruby will be the first digital standalone, self-compassion-based intervention designed to reduce internalized weight bias. Owing to its standalone digital delivery, Ruby may be a highly scalable treatment for internalized weight bias that can be delivered on its own or combined with other treatments. We expect Ruby to be accessible to many, as participants can access the digital intervention at times of the day that are the most convenient in their schedule and are not burdened by in-person time commitments, which can be a barrier for participants with competing demands on their time and resources. If efficacious, Ruby will be poised to expand a burgeoning body of literature related to psychological intervention in this area. ClinicalTrials.gov NCT04678973; https://clinicaltrials.gov/ct2/show/NCT04678973. DERR1-10.2196/31307.


Increase in oxidative damage to lipids and proteins in skeletal muscle of uremic patients.
Muscle weakness and reduced exercise capacity are frequent complaints of patients with chronic uremia. Several lines of evidence have suggested that chronic uremia result in a state of increased oxidative stress. Reactive oxygen species (ROS) and free radicals are capable of damaging lipids and proteins but it remains unclear whether oxidative damage plays a role in the skeletal myopathy commonly seen in chronic uremia. In this cross-sectional study, we compared the levels of oxidative damage to proteins and lipids of skeletal muscle from 40 chronic uremic patients and 20 age- and sex-matched healthy subjects. Protein carbonyls were determined by a spectrophotometric method to assess the oxidative damage to proteins. Our results showed that the mean content of protein carbonyls in skeletal muscles was significantly elevated in the hemodialysis patients (3.78+/-0.14 nmol of 2,4-dinitrophenyl-hydrazone per mg of protein) as compared to healthy controls (2.97+/-0.28 nmol per mg of protein, p = 0.017 vs normal controls). In addition, we found that the mean malondialdehyde (MDA) level was also significantly increased in the uremic patients compared to healthy controls. Further analysis revealed that there was an age-dependent increase in both oxidative damages in these patients. Regression analysis between plasma protein carbonyl and MDA levels showed a significant correlation between these two parameters (r = 0.43, p = 0.002). The finding of increased oxidative damage to protein and lipids provide support that oxidative damage may play a role in the pathogenesis of skeletal myopathy in chronic uremic patients on hemodialysis.


Linezolid as salvage therapy for central nervous system infections due to methicillin-resistant Staphylococcus aureus at two medical centers in Taiwan.
Methicillin-resistant Staphylococcus aureus (MRSA)-associated central nervous system infections are potentially devastating. Linezolid has good penetration into cerebrospinal fluid and brain tissue. In clinical practice, linezolid may be used to treat central nervous system infections caused by MRSA resulting from glycopeptide intolerance or treatment failure. However, the clinical experience of linezolid in treating MRSA related central nervous system infections is scarce. From 2006 to 2016, patients aged ≥20 years who had central nervous system infections caused by MRSA treated with linezolid for more than 24 hours were retrospectively included from two medical centers. The demographic details, treatment response, side effects, and relapse of infection were reviewed. Sixty-six patients with proven CNS infection caused by MRSA were treated with linezolid. The mean age was 53.3 years. The diagnoses in this cohort consisted of brain abscesses (n = 19, 28.8%), spinal epidural abscess (n = 18, 27.3%), meningitis only (n = 12, 18.2%), meningitis with brain epidural abscess (n = 9, 13.6%), and spine device-related infection (n = 5, 7.6%). The main reasons to prescribe linezolid were glycopeptide treatment failure (51.5%) and glycopeptide allergy (48.5%). Ninety-one percent of patients were treated with linezolid for more than 14 days. The in-hospital mortality rate was 13.6%. The relapse rate after treatment was 16.7%. Drug-related adverse events (mainly cytopenia) were observed in 27.3% of patients, but none of the adverse events was fatal. In our retrospective study, linezolid demonstrated promising effect as a salvage therapy for central nervous system infection caused by MRSA, whether due to drug allergy or glycopeptide treatment failure.


Fast dissociation of phe-tRNA synthetase from Aspergillus nidulans immobilized on sepharose-6B column by NaCl.
Phenylalanyl-tRNA2) synthetase from Aspergillus nidulans was efficiently immobilised to sepharose 6B column containing phenylalanine as the ligand. NaCl was found to be a potent dissociating agent for the immobilised enzyme. While 0.5 M NaCl in discontinuous elution showed a slow impetus on dissociation giving a plateaux profile, a solution of 0.8 M NaCl made the elution rapid giving a sharp peak. On the other hand, in a gradient (continuous) elution the rapidity of dissociation was found to be enhanced with the increase in the difference of the two concentrations. The result suggests that Na+ ions interact with the protein binding site of the ligand eventually dissociating the enzyme molecule by disrupting the covalent bond without affecting its normal catalytic activity.


Aberrant Expression of lncRNA ( HOXA11-AS1) and Homeobox A ( HOXA9, HOXA10, HOXA11, and HOXA13) Genes in Infertile Women With Endometriosis.
This study aimed to study the expression of homeobox (HOX)A11-AS1 ( HOXA11 antisense RNA) long noncoding RNA (lncRNA) and the expression of homeobox A ( HOXA9, HOXA10, HOXA11, and HOXA13) genes in the eutopic (EU) and ectopic (EC) endometria of women with peritoneal endometriosis. A total of 30 women undergoing laparoscopic surgery for peritoneal endometriosis and 15 infertile women without endometriosis were enrolled in this study. Peritoneal EC tissue samples were obtained through surgery. The EU tissues were obtained by curettage. The EC and EU lncRNA and messenger RNA (mRNA) expression levels were measured using real-time reverse transcriptase-polymerase chain reaction. The HOXA11-AS1 lncRNA and HOXA9, HOXA10, HOXA11, and HOXA13 mRNA were expressed at significantly lower levels in the EU than in the EC, that is, in women with peritoneal endometriosis ( P < .05). The expression levels of HOXA10 and HOXA11 in the EU were significantly lower in women with peritoneal endometriosis compared to the control group participants ( P < .05), whereas the levels of lncRNA ( HOXA11-AS1), HOXA9, and HOXA13 did not differ significantly between the 2 patient groups ( P > .05). In conclusion, the study findings suggest that HOXA11-AS1 lncRNA may play a role in the development of peritoneal endometriosis, but HOXA11-AS1 may not influence endometrial receptivity in endometriosis-associated infertility.


[Premorbid intelligence diagnosis with the MWT-B(Multiple Choice Word Test-B) in patients with Alzheimer disease].
The usefulness of the multiple-choice word test (MWT-B) was tested as a measure for premorbid intelligence in 107 patients with probable Alzheimer's disease following the NINCDS-ADRDA criteria. The patients were allocated to three groups according to severity of dementia: mild (n = 40), moderate (n = 41) and severe (n = 26). Dementia severity was assessed with the Mini Mental State Test (MMST). The mean of the raw values of the MWT-B (maximum 37) in the group with mild dementia was 28.0 (SD = 5.57), in the group with moderate dementia 23.3 (SD = 8.01), and in the group with severe dementia 6.7 (SD = 8.44), indicating a parallel worsening with the other tests. The MWT-B value of the whole sample correlated with the MMST value (r = 0.70); a significant correlation still existed in patients with mild and moderate dementia. These results confirm that the MWT-B is relevant for dementia. The rate of cerebral glucose metabolism, measured with positron emission tomography (PET) and 18F-fluorodeoxy-glucose (FDG) correlated significantly with the MWT-B scores in the Alzheimer-sensitive temporoparietal region (r = 0.43; P = 0.001) and frontal brain region (r = 0.37; P < 0.05). Whether or not it can be used as a screening measure of dementia will have to be decided on the basis of its scales for sensitivity and specificity.


Prosorhynchoides borealis Bartoli, Gibson & Bray, 2006 (Digenea: Bucephalidae) cercariae from Abra prismatica (Mollusca: Bivalvia) in Icelandic waters.
This paper reports the adult stage of Prosorhynchoides borealis (Digenea) from Lophius piscatorius in Icelandic waters and infections with the larval stages (sporocysts and cercariae) found for the first time in the bivalve Abra prismatica (Semelidae). The previously known first intermediate host was Abra alba (Semelidae). Ribosomal DNA sequencing studies on all three life stages of the parasite (cercariae, metacercariae, adults) were performed to confirm their identites. Morphometric measurements confirmed that the adult worms belong to the newly described species P. borealis. Prosorhynchoides borealis sporocysts filled with cercariae were found in 16% of A. prismatica bivalves sampled at depths between 34 and 93 m off South Iceland. Prevalence ranged from 0 to 44% between different localities. The parasite was found only in the larger bivalves. Extensive sporocyst infection in the haemocoel of the foot caused mechanical muscle damage with subsequent degeneration and necrosis. Other tissues, including the digestive gland, nephridia, gills and intestine, were less heavily infected. Only focal necrosis was observed in the digestive gland, nephridia and gills, and local atrophy in the intestine. Cercariae were also observed in the lumen of both the stomach and intestine. This is the first report of A. prismatica as an alternative first intermediate host for P. borealis. Ribosomal DNA sequence data reveals 100% homology in the data between cercariae, metacercariae and adult digeneans, supporting the morphological data suggesting that all stages belong to the same species.


An in vitro analysis of disintegration times of different formulations of olanzapine orodispersible tablet: a preliminary report.
Orodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies. Disintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab(®) was included as a non-olanzapine ODT comparator. Eleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vitro for formulation composition, manufacturing method, disintegration and dissolution characteristics, and formulation differences in comparison with freeze dried Zydis(®) ODT. Automated dissolution test equipment captured ODT dissolution rates by measuring real-time release of active ingredient. A high-speed video camera was used to capture tablet disintegration times in warm simulated saliva. The main outcome measure was the disintegration and dissolution characteristics of the ODT formulations. The ODT manufacturing method was associated with time to disintegrate; the fastest were freeze dried tablets, followed by soft compressed tablets and then hard/dense tablets. Olanzapine Zydis(®) was the only ODT that completely disintegrated in less than 4 s for all strengths (5, 10, 15, and 20 mg), followed by 5-mg Prolanz FAST(®) (12 s) and then risperidone ODT 4 mg (40 s). Reasons for slow dissolution of the olanzapine generics may include low product potency, excipient binding, excipient solubility, active ingredient particle size and incomplete disintegration. Differences in the formulation and manufacturing process of olanzapine ODTs appear to have a strong influence on the disintegration time of the active compound; differences that may potentially impact their use in clinical practice.


The transformation of the agricultural population and the urbanisation process in China.
"Nine causes for the occurrence of surplus agricultural labour with the modernisation of agriculture have been identified. Several solutions to this problem are presented. Urbanisation of the agricultural population in a way suited to China's characteristics is necessary, important and possible." An example of labor saving through mechanization in Heilongjiang province is presented.


Are reliability, reproducibility and validity the correct terms to assess the correctness of dietary studies?
Nutritional studies often use the terms reliability, reproducibility and validity to indicate the correctness of the study. These terms do not appear to have a universal meaning to all researchers. The components of a dietary study are the input, the data collection instrument and the compiled data. Frequently the data collection questionnaire/tool/instrument is tested for reliability, reproducibility or validity. The data collection questionnaire/tool/instrument is simply a structure, a vehicle for gathering data. An argument is presented that demonstrates the reasons that such a structure cannot be tested for reliability, reproducibility or validity. The logical approach to the use of the terms reliability, reproducibility and validity is presented. Reliability refers to the input component of the study, reproducibility may or may not lead to strengthening the study and validity refers to the truthfulness of the database generated. Validity must be derived from reliable and reproducible data.


Quantifying Alumina Nanoparticle Dispersion in Hybrid Carbon Fiber Composites Using Photoluminescent Spectroscopy.
Composites modified with nanoparticles are of interest to many researchers due to the large surface-area-to-volume ratio of nano-scale fillers. One challenge with nanoscale materials that has received significant attention is the dispersion of nanoparticles in a matrix material. A random distribution of particles often ensures good material properties, especially as it relates to the thermal and mechanical performance of composites. Typical methods to quantify particle dispersion in a matrix material include optical, scanning electron, and transmission electron microscopy. These utilize images and a variety of analysis methods to describe particle dispersion. This work describes how photoluminescent spectroscopy can serve as an additional technique capable of quickly and comprehensively quantifying particle dispersion of photoluminescent particles in a hybrid composite. High resolution 2D photoluminescent maps were conducted on the front and back surfaces of a hybrid carbon fiber reinforced polymer containing varying contents of alumina nanoparticles. The photoluminescent maps were analyzed for the intensity of the alumina R1 fluorescence peak, and therefore yielded alumina particle dispersion based on changes in intensity from the embedded nanoparticles. A method for quantifying particle sedimentation is also proposed that compares the photoluminescent data of the front and back surfaces of each hybrid composite and assigns a single numerical value to the degree of sedimentation in each specimen. The methods described in this work have the potential to aid in the manufacturing processes of hybrid composites by providing on-site quality control options, capable of quickly and noninvasively providing feedback on nanoparticle dispersion and sedimentation.


The Effects of Right Hemisphere Brain Damage on Question-Asking in Conversation.
Right hemisphere brain damage (RHD) can cause challenges with information gathering. Cognitive processes aid in implicit and explicit information gathering, yet the relationship between these processes and question-asking, the most explicit avenue of information gathering, has not been explored. The purpose of this exploratory descriptive study was to test the hypothesis that adults with RHD differ from controls in the types of questions produced during a conversational discourse task and whether observed differences are associated with cognitive limitations. Adults with RHD (n = 15) and controls (n = 15) participated in a 5-min "first-encounter conversation" and were assessed for attention, memory, executive functioning (EF), visuospatial skills, and language domains using the Cognitive Linguistic Quick Test (CLQT). Questions produced during the conversation were coded and tallied by type: polar (yes/no), content (wh-), or alternative (A or B) using Computerized Language Analysis programs. Groups were compared on total questions used, use of questions by type, and CLQT domain scores; associations were computed between cognitive domain scores and question types. Compared with controls, adults with RHD used half as many questions overall and scored significantly lower on the attention, executive function, and visuospatial domains of the CLQT. For the RHD group, there was a significant correlation between EF scores and the production of content and polar questions. The frequency of question-asking is important to understanding the communication profile in adults with RHD. Executive function, attention, and, to a lesser extent, visuospatial capabilities may contribute to question-asking behaviors in conversation in this population. The RHD Framework for Asking Questions is proposed to illustrate the potential areas of deficit in the question-asking process after RHD.


Perceptions of clinicians and staff about the use of digital technology in primary care: qualitative interviews prior to implementation of a computer-facilitated 5As intervention.
Digital health interventions using hybrid delivery models may offer efficient alternatives to traditional behavioral counseling by addressing obstacles of time, resources, and knowledge. Using a computer-facilitated 5As (ask, advise, assess, assist, arrange) model as an example (CF5As), we aimed to identify factors from the perspectives of primary care providers and clinical staff that were likely to influence introduction of digital technology and a CF5As smoking cessation counseling intervention. In the CF5As model, patients self-administer a tablet intervention that provides 5As smoking cessation counseling, produces patient and provider handouts recommending next steps, and is followed by a patient-provider encounter to reinforce key cessation messages, provide assistance, and arrange follow-up. Semi-structured in-person interviews of administrative and clinical staff and primary care providers from three primary care clinics. Thirty-five interviews were completed (12 administrative staff, ten clinical staff, and 13 primary care providers). Twelve were from an academic internal medicine practice, 12 from a public hospital academic general medicine clinic, and 11 from a public hospital HIV clinic. Most were women (91 %); mean age (SD) was 42 years (11.1). Perceived usefulness of the CF5As focused on its relevance for various health behavior counseling purposes, potential gains in counseling efficiency, confidentiality of data collection, occupying patients while waiting, and serving as a cue to action. Perceived ease of use was viewed to depend on the ability to accommodate: clinic workflow; heavy patient volumes; and patient characterisitics, e.g., low literacy. Social norms potentially affecting implementation included beliefs in the promise/burden of technology, priority of smoking cessation counseling relative to other patient needs, and perception of CF5As as just "one more thing to do" in an overburdened system. The most frequently cited facilitating conditions were staffing levels and smoking cessation resources and training; the most cited hindering factors were visit time constraints and patients' complex health care needs. Integrating CF5As and other technology-enhanced behavioral counseling interventions in primary care requires flexibility to accommodate work flow and perceptions of overload in dynamic environments. Identifying factors that promote and hinder CF5As adoption could inform implementation of other CF behavioral health interventions in primary care.


[Experimental studies of direct pulp capping in permanent teeth with incompletely formed apices].
In permanent teeth described as having incompleted roots, dentin is still in the process of deposition on internal dentin walls and the root is in the process of completion. The purpose of this study of dog's immature permanent teeth was to investigate pulp healing and continuous root and internal dentin-wall developments after direct pulp capping with two types of calcium hydroxide paste on mechanically exposed pulp. Material and methods In this study, 148 vital permanent premolars with incompletely formed apices were obtained from 26 dogs (6 months old). The animals were generally anesthetized with 5% sodium pentobarbital, and a cavity was prepared on the occlusal surface of each experimental tooth using an air turban handpiece with diamond bur. After the cavity preparation, the central pulp horn of each tooth was mechanically exposed with a sterile round bur (ISO No. 007, 2/0). In experimental teeth on the right side, a calcium hydroxide-iodoform paste "Calvital" was applied on the exposed pulp, in experimental teeth on the left side, the exposed pulp was capped with a hard-setting calcium hydroxide paste "Dycal". The cavities were lined with first a zinc-oxide eugenol cement and then a zinc-phosphate cement. Then the cavities were filled with silver amalgam. The dogs were sacrificed by means of sodium pentobarbital at intervals of 3, 7, 14, 28, and 56 days after direct pulp capping. Their jaws and teeth were removed, fixed with formalin, and 100 cases out of 148 teeth with bones from 20 dogs were decalcified, and embedded in celloidin. Each specimen was serially sectioned, stained with hematoxylin-eosin, thionin-picric acid and van Gieson's stain, and evaluated microscopically. In order to identify postoperative dentin formation, intravenous injections of tetracycline were administered to the remaining 6 dogs (48 teeth) at various intervals after the experimental procedure. Two dogs were sacrificed each of the experimental periods. Specimens were embedded in resin and sectioned to a thickness of 50 microns. Undecalcified ground sections were observed by contact microradiography, and tetracycline labeling was evaluated by ultraviolet light. Results and Conclusion 1. Pathological evaluations of the 2 groups "Calvital" group: 49 (98.0%) of 50 cases were evaluated as good, and 1 case (2.0%) as moderately good. "Dycal" group: 31 (62.0%) of 50 cases were evaluated as good, 15 (30.0%) as moderately good, and 4 (8.0%) as bad.(ABSTRACT TRUNCATED AT 400 WORDS)


Survival of hepatitis C virus in syringes: implication for transmission among injection drug users.
We hypothesized that the high prevalence of hepatitis C virus (HCV) among injection drug users might be due to prolonged virus survival in contaminated syringes. We developed a microculture assay to examine the viability of HCV. Syringes were loaded with blood spiked with HCV reporter virus (Jc1/GLuc2A) to simulate 2 scenarios of residual volumes: low void volume (2 microL) for 1-mL insulin syringes and high void volume (32 microL) for 1-mL tuberculin syringes. Syringes were stored at 4 degrees C, 22 degrees C, and 37 degrees C for up to 63 days before testing for HCV infectivity by using luciferase activity. The virus decay rate was biphasic (t1/2alpha= 0.4 h and t1/2beta = 28 hh). Insulin syringes failed to yield viable HCV beyond day 1 at all storage temperatures except 4 degrees , in which 5% of syringes yielded viable virus on day 7. Tuberculin syringes yielded viable virus from 96%, 71%, and 52% of syringes after storage at 4 degrees, 22 degrees, and 37 degrees for 7 days, respectively, and yielded viable virus up to day 63. The high prevalence of HCV among injection drug users may be partly due to the resilience of the virus and the syringe type. Our findings may be used to guide prevention strategies.


The influence of the biarticularity of the gastrocnemius muscle on vertical-jumping achievement.
Hypotheses concerning the influence of changes in the design of the human musculoskeletal system on performance cannot be tested experimentally. Computer modelling and simulation provide a research methodology that does allow manipulation of the system's design. In the present study this methodology was used to test a recently formulated hypothesis concerning the role of the biarticularity of the gastrocnemius muscle (GAS) in vertical jumping [Bobbert and van Ingen Schenau, J. Biomechanics 21, 249-262 (1988)]. This was done by comparing maximal jump heights for a model equipped with biarticular GAS with a model equipped with a monoarticular GAS. It was found that jump height decreased by 10 mm when GAS was changed into a monoarticular muscle. Thus, the hypothesis formulated by Bobbert was substantiated, although quantitatively the effect is small. Our result differs from that of Pandy and Zajac [J. Biomechanics 24, 1-10 (1991)], who performed similar model calculations. It is shown that the results described by these authors can be explained from the moment-arm-joint-angle relation of GAS at the knee in their model.


Polymorphism, pseudopolymorphism, and amorphism of peracetylated alpha-, beta-, and gamma-cyclodextrins.
Polymorphism, pseudopolymorphism, and amorphism of hexakis(2,3,6-tri-O-acetyl)-alpha-cyclodextrin (TAalphaCyD), heptakis(2,3,6-tri-O-acetyl)-beta-cyclodextrin (TAbetaCyD), and octakis(2,3,6-tri-O-acetyl)-gamma-cyclodextrin (TAgammaCyD) were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and optical microscopy. An anhydrous and a bi-hydrate crystalline forms of TAalphaCyD, two monotropic anhydrous polymorphs and three pseudopolymorphs (i.e. methanolate, hydrate, and isopropanolate-hydrate) of TAbetaCyD, as well as two monotropic anhydrous polymorphs and isostructural pseudopolymorphs (e.g. hydrate and isopropanolate-hydrate) of TAgammaCyD were isolated and characterized. The amorphous forms of each TACyD were also obtained. Thermal data for desolvation of TAalphaCyD.2H2O and TAbetaCyD.CH3OH were reconciled with their crystal packing features. Melting temperatures and enthalpies of the crystalline forms of each TACyD can be referred to for possible solid-state interactions with drugs.


Association among metabolic status, oxidative stress, milk yield, body condition score and reproductive cyclicity in dairy buffaloes.
The aim of this study was to determine the metabolic status, stress and ovarian activity through progesterone profile in dairy buffalo as influenced by post-partum days, body condition score (BCS) and lactation number. A total of 45 dairy buffaloes were involved and divided into three factors based on their BCS (2.5, 3.0 and 3.5, respectively), lactation number (1, 2 and 3, respectively), and post-partum intervals (14, 28, 42 and 56, respectively). Based on findings, from day 14 to day 56 after parturition, blood glucose, cholesterol and triglyceride levels increased significantly (p < .01), while malondialdehyde (MDA) and cortisol levels decreased significantly (p < .05) on day 56 of the trial. With increased BCS levels, milk yield, blood metabolites and progesterone improved significantly (p < .05), whereas stress indicators decreased significantly (p < .01). Blood metabolites, progesterone and milk production were significantly (p < .01) higher and stress indicators (MDA and cortisol) were significantly (p < .01) lower in lactation stage. Buffaloes with a greater lactation stage and growing post-partum stage had better blood metabolite and progesterone concentrations and less stress. It was concluded that better BCS and increased lactation stage have significant impact on milk yield, stress reduction and restoration of ovarian activity in buffaloes during post-partum period.


[Indications for prophylactic cranial irradiation in patients with small cell lung cancer].
Brain metastases are one of the important causes of failure in the treatment of SCLC patients. Intracranial metastases are reported in 10% of the newly diagnosed SCLC pts. Further 20% brain metastases develop during therapy. Autopsy studies showed that 40%-60% of pts had evidence of intracranial spread at the time of death. The frequency of brain metastases increases with the duration of survival, reaching a probability of 80% after 2 years of observation. The high risk of brain metastases which developed in spite of chemotherapy was the reason of introducing PCI to the treatment. PCI reduces the risk of brain metastases to less than 10%, but unfortunately, does not prolong median survival. Probably this is due to the fact, that in the majority of cases the brain is one of many sites of metastases at the time of progression. In addition, in some pts brain metastases developed in spite of PCI and/or brain toxicity may develop after this treatment. Thus, up till now the role of PCI in the treatment of SCLC pts remains controversial. The indication for this treatment could improve if we have more exact information which pts have the greatest probability do develop metastases restricted to the brain only. This question was the main aim of our study.


Brush cytology vs. endoscopic biopsy for the surveillance of Barrett's esophagus.
Periodic surveillance with systematic biopsies is recommended for patients with Barrett's esophagus. Brush cytology has been proposed as a simple inexpensive component of endoscopic surveillance, which may also detect abnormalities prior to detection of histologic abnormalities. The aim of the current study was to determine whether brush cytology provides any additional value over endoscopic surveillance biopsies in patients with Barrett's esophagus. This retrospective cohort study included 530 patients with Barrett's esophagus undergoing endoscopic surveillance with paired biopsy and cytology specimens at the Cleveland Clinic between January 1994 and July 2008. The main outcome measures were sensitivity, specificity, and concordance rates of cytology and histology. Sensitivity of cytology for any dysplasia was 49 % and specificity was 95 %. However, sensitivity was 82 % for detection of high grade dysplasia/adenocarcinoma but only 31 % for low grade/indefinite for dysplasia. The concordance rate between cytology and histology was 80 %. Histology had a higher dysplasia detection rate than cytology (24.0 % vs. 15.7 %, respectively; P <0.0001). Cytology has excellent specificity and good sensitivity for the detection of high grade dysplasia/adenocarcinoma but poor sensitivity for low grade dysplasia. There was substantial concordance between cytology and histology for the detection of dysplasia. However, histology had a higher dysplasia detection rate and therefore the value of routine cytology in the surveillance of Barrett's esophagus is questionable.


Relationship between total serum immunoglobulin E levels, fractional exhaled breath nitric oxide levels and absolute blood eosinophil counts in atopic and non-atopic asthma: a controlled comparative study.
Asthma is a prevalent non-communicable disease both in low- and high-income countries, including Nepal. Total serum immunoglobulin E levels and peripheral blood absolute eosinophil counts are known inflammatory markers of asthma. Fractional exhaled nitric oxide measurement in breath has also been proposed as a non-invasive biomarker to assess eosinophilic airway inflammation. This study explores the correlation between these three variables with the intent that one may replace the other in resource-limited setups. This prospective controlled trial evaluated 314 subjects with and without asthma, with the asthma group sub-divided into atopic and non-atopic categories. Total serum immunoglobulin E level, absolute eosinophil count in peripheral blood and fractional exhaled nitric oxide level were measured in all categories. The geometric mean of immunoglobulin E levels, absolute eosinophil count and fractional exhaled nitric oxide were 221.07 ± 774.55 IU/mL, 214 ± 360/uL and 37 ± 49 ppb in the asthma group and 59.13 ± 174.32 IU/mL, 164 ± 137/uL and 12 ± 21 ppb in the control group, respectively. Significantly higher levels were seen in the asthma group for total serum immunoglobulin E (p < 0.001), AEC (p = 0.002) and FENO (p < 0.001) levels. Total serum immunoglobulin E levels, absolute eosinophil count and fractional exhaled nitric oxide were 436.79 ± 822.40 IU/mL, 269 ± 395/uL and 76 ± 52 ppb in atopic asthma group. Similarly, total serum immunoglobulin E levels, absolute eosinophil count and fractional exhaled nitric oxide were 131.17 ± 692.96 IU/mL, 182 ± 328/uL and 23 ± 22.5 ppb in non-atopic asthma group. Significantly higher levels were seen in all three variables: tIgE (p < 0.001), AEC (p = 0.008) and FENO (p < 0.001). A moderate degree of positive correlation was identified between tIgE and FENO50 (Spearman's rho = 0.461) and tIgE and AEC (Spearman's rho = 0.315) with only small correlation between FENO50 and AEC (Spearman's rho = 0.299). tIgE levels, FENO50 and AEC levels are higher in asthma, specifically in the atopic phenotype, as compared to normal. Total serum IgE levels have moderate correlation with FENO50 and AEC but FENO50 and AEC are weakly correlated.


The role of S100B/RAGE-enhanced ADAM17 activation in endothelial glycocalyx shedding after traumatic brain injury.
Traumatic brain injury (TBI) remains one of the main causes for disability and death worldwide. While the primary mechanical injury cannot be avoided, the prevention of secondary injury is the focus of TBI research. Present study aimed to elucidate the effects and mechanisms of S100B and its receptor RAGE on mediating secondary injury after TBI. This study established TBI animal model by fluid percussion injury in rats, cell model by stretch-injured in astrocytes, and endothelial injury model with conditioned medium stimulation. Pharmacological intervention was applied to interfere the activities of S100B/RAGE/ADAM17 signaling pathway, respectively. The expressions or contents of S100B, RAGE, syndecan-1 and ADAM17 in brain and serum, as well as in cultured cells and medium, were detected by western blot. The distribution of relative molecules was observed with immunofluorescence. We found that TBI could activate the release of S100B, mostly from astrocytes, and S100B and RAGE could mutually regulate their expression and activation. Most importantly, present study revealed an obvious increase of syndecan-1 in rat serum or in endothelial cultured medium after injury, and a significant decrease in tissue and in cultured endothelial cells, indicating TBI-induced shedding of endothelial glycocalyx. The data further proved that the activation of S100B/RAGE signaling could promote the shedding of endothelial glycocalyx by enhancing the expression, translocation and activity of ADAM17, an important sheddase, in endothelial cells. The damage of endothelial glycocalyx consequently aggravated blood brain barrier (BBB) dysfunction and systemic vascular hyper-permeability, overall resulting in secondary brain and lung injury. TBI triggers the activation of S100B/RAGE signal pathway. The regulation S100B/RAGE on ADAM17 expression, translocation and activation further promotes the shedding of endothelial glycocalyx, aggravates the dysfunction of BBB, and increases the vascular permeability, leading to secondary brain and lung injury. Present study may open a new corridor for the more in-depth understanding of the molecular processes responsible for cerebral and systemic vascular barrier impairment and secondary injury after TBI.


Process and tubercle fractures of the hindfoot.
Process and tubercle fractures of the talus and calcaneus can be a source of significant pain and dysfunction. Successful management requires extensive knowledge of the complex osseoligamentous anatomy of the hindfoot. The large posterior process of the talus is composed of a medial and a lateral tubercle; an os trigonum may exist posterior to the lateral tubercle. The talus has a lateral process that articulates with the fibula and subtalar joint; the calcaneus possesses a frequently injured anterior process that articulates with the cuboid. Injury to these hindfoot structures is caused by inversion and eversion of the ankle, which can occur during athletic activity. These injuries often are misdiagnosed as ankle sprains. A high degree of clinical suspicion is warranted, and specialized radiographs or other imaging modalities may be required for accurate diagnosis. Nonsurgical management with cast immobilization is frequently successful when the fracture is correctly diagnosed acutely. Large fragments may be amenable to open reduction and internal fixation. Untreated, chronic injuries can cause significant pain and functional impairment that may be improved substantially with late surgical intervention.


Clostridium difficile Causing Empyema.
Extraintestinal Clostridium difficile infection (CDI) is extremely uncommon. High mortality and poor outcomes have been observed among individuals with this rare medical condition. Empyema is one of the extraintestinal manifestations of CDI. Possible mechanisms to develop this parapneumonic effusion are aspiration and contamination of the chest tube. We present a 42-year-old Hispanic male with C. difficile empyema without any prior history of CDI.


Selective targeting of G-quadruplex using furan-based cyclic homooligopeptides: effect on c-MYC expression.
Quadruplex-specific molecules can serve as suitable drugs in cancer therapy. We have synthesized a pair of furan-based cyclic homooligopeptides, ligand 1 and ligand 2, to specifically target G-quadruplexes. We have shown by CD spectroscopy and UV melting that these ligands can effectively induce G-quadruplex structures in the G-rich 22-mer c-MYC DNA sequence and further stabilize the structure. Equilibrium binding constants measured by isothermal titration calorimeter methods indicate a high affinity of the ligands for the quadruplex structures (K ∼ 10(7) M(-1)) and no affinity for the duplex DNA, demonstrating that these ligands are selective for G-quadruplex structures. Surface plasmon resonance was also used to compute the binding while fluorescence resonance energy transfer-based assay was additionally used to confirm the selectivity. Moreover, using real time PCR we observed up to 90% downregulation of c-MYC transcripts after 24 h of ligand treatment in HeLa cells. Using a luciferase assay we show the downregulation of the protein levels. Fluorescent-assisted cell sorter-based cell cycle analysis showed a prominent arrest of cells in the sub-G1 stage upon treatment of ligands that leads toward apoptosis. Altogether, these experiments support the hypothesis that the present molecules are effective in specifically binding and stabilizing quadruplexes and provide a suitable scaffold to develop into a quadruplex-targeting therapeutic agent.


Chemometric evaluation of brompheniramine-tannate complexes.
The objective of the current study was to evaluate the performance of Raman and near-infrared (NIR) techniques combined with chemometrics in characterizing the critical quality attributes of brompheniramine (BP)-tannate complexes. Seven complexes were prepared and evaluated for chemical interactions, solubilities, dissolutions, and spatial distributions by NIR chemical imaging (CI). Principal component analysis (PCA) was applied before either partial least squares regression (PLSR) or principal component regression (PCR) models were developed. Complexation was confirmed by Fourier transform IR analysis to yield complexes of lower drug solubilities and sustained-release characteristics in alkaline media. PCA results showed better discrimination ability by NIR than by Raman spectroscopy. Compared with PCR, the PLSR predictions errors, calculated from the Raman and NIR data with second-derivative pretreatment, showed lesser values of 2.68, 0.37, 1.79, and 5.60 and 0.58, 0.25, 0.93, and 0.58 for complex solubilities in acidic and alkaline media and percentages dissolved after 1 and 20 h, respectively. In addition, good correlation (>0.95) was obtained for predicting the drug concentration using PLSR score images explaining the validity of the NIR-CI model for spatial quantitation of BP within its tannate complexes. In conclusion, the chemometric analysis of NIR and/or Raman spectra represented an innovative approach to determine the tannate complexation variability.


Construction of a circular single-stranded DNA template containing a defined lesion.
We report a concise and efficient method to make a circular single-stranded DNA containing a defined DNA lesion. In this protocol, phagemid DNA containing Uracil is used as a template to synthesize a complementary DNA strand using T7 DNA polymerase and an oligonucleotide primer including a site-specific DNA lesion. The ligated lesion-containing strand can be recovered after the phage-derived template DNA is degraded by treatment with E. coli Uracil DNA glycosylase and Exonucleases I and III. The resulting product is a circular single-stranded DNA containing a defined DNA lesion suitable for in vitro translesion replication assays.


How do proteins fold?
This article emphasizes the importance of getting students to understand the ways in which polypeptides fold to form protein molecules with complex higher-ordered structures. Modern views on how this folding occurs in vitro and in the cell are summarized and set within an appropriate biological context.


Jackstone: A Calculus "Toy" in the Bladder. A Case Report of Rare Entity and Comprehensive Review of the Literature.
An uncommon type of urinary calculus, Jackstone was named after its distinct resemblance to the children's game "Jacks." It typically involves the bladder and, to a lesser extent, the upper urinary tract. Herein, we report a case of Jackstone vesical calculus in a 75-year-old male undergoing elective open prostate surgery for benign prostate hyperplasia refractory to medical treatment. Preoperative clinical examination revealed intermittent gross hematuria and symptoms suggestive of bladder outlet obstruction, while radiological investigation confirmed the presence of a solitary star-shaped spike-like bladder stone along with an overly enlarged prostate. Following open simple prostatectomy and concomitant intact stone removal, our patient made an uneventful postoperative recovery. This case highlights an infrequent subtype of bladder lithiasis and further expands upon the importance of promptly treating the underlying cause once this rare entity is detected. A comprehensive review of the literature on Jackstone calculi is further presented.


Sex differences and estradiol involvement in hyperalgesia and allodynia in an experimental model of fibromyalgia.
Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome. Its prevalence in women is higher than in men possibly by hormonal factors given that symptoms are aggravated during sex hormone-related events, such as the premenstrual period, pregnancy, postpartum or menopause. The aim of the present study was to investigate whether hyperalgesia and allodynia, in reserpine-induced experimental FM, depend on sex, estrous cycle, ovariectomy and replacement with 17β-estradiol. To fulfill this objective, we compared males, intact females with known estrous cycle phases and ovariectomized (OVX) rats treated with 17β-estradiol. Data demonstrated that reserpine administration disrupted the normal estrous cycle and produced that all females entered metestrus/diestrus. In addition, this treatment leads to muscle hyperalgesia and tactile allodynia in a similar manner in male and intact female rats. However, the absence of ovarian hormones (in OVX rats) increased muscle nociception. 17β-estradiol (2.5-10μg/rat) produced antihyperalgesic and antiallodynic effects 24h, but not 8h, after its administration, suggesting a genomic mechanism. The present results support the validity of the reserpine-induced FM model for searching alternatives of treatment, particularly during endocrine phases when pain is exacerbated such as menopause, and that 17β-estradiol replacement might be useful.


Strategies for effective management of depression in primary care. Based on a presentation by Michael S. Klinkman, MD.
The diagnosis and treatment of depressive disorders are challenges to the primary care physician because of the condition's high prevalence and chronicity, the frequent occurrence of medical and mental health comorbidities, patients' unwillingness to disclose a mental health history, and cost. Primary care physicians also cite lack of time and managed care policies as major barriers to improving outcomes in patients with depression. A potentially more effective approach to treating depression is health management, rather than traditional disease management. In this approach, the focus of care is patients' functional status and quality of life rather than the treatment of a specific health condition in isolation; patients are actively involved with care, and care choices are driven by competing demands. Another approach that may help improve outcomes in depression is the Recognize, Assess, Categorize, and Treat (ReACT) strategy, which is an efficient way to detect and triage patients with depressive disorders according to the severity of illness. Adjunctive aids, such as the use of support staff, monitoring systems, and collaborative care with mental health specialists, also have great potential for improving primary care physicians' effectiveness in treating depression.


Involvement of specific transport system on uptake of lactone form of SN-38 in human intestinal epithelial cell line Caco-2.
The aim of this study was to elucidate the characteristics of the transport of lactone and carboxylate forms of SN-38 (SN-38L and SN-38C, respectively), a metabolite of irinotecan hydrochloride (CPT-11), with the human intestinal epithelial cell line, Caco-2. We examined SN-38L and SN-38C uptake from the apical side into Caco-2, and the effects of various compounds on the uptake of SN-38L. SN-38L and SN-38C in the cells were determined by HPLC with a fluorescence detector. When either SN-38L (0.5 µM) or SN-38C (0.5 µM) was added extracellularly at 37°C, the accumulation of SN-38L into the cells was about 10-fold higher than that of SN-38C, suggesting a dominant role of the lactone form in the uptake of SN-38 into Caco-2. The accumulation of SN-38L in Caco-2 increased time-dependently up to 10 min at 37°C, whereas the accumulation markedly decreased at 4°C. The initial uptake rate of SN-38L approached saturation at high concentrations with Michaelis-Menten constant and 'Hill coefficient,' 2.84±1.00 μM and 2.13±1.14, respectively (mean±S.E.). The accumulation of SN-38L was markedly inhibited by baicalin, an active ingredient of a Chinese herbal medicine, Hange-Shashin-To, as well as CPT-11. The type of inhibition by baicalin was competitive. In contrast, concomitant sulfobromophthalein, taurocholate and estrone 3-sulfate significantly increased SN-38L uptake. These results suggest that apical uptake of SN-38 by Caco-2 is dominantly performed as a lactone form through a specific transporter, which is competitively inhibited by baicalin.


Unusual presentation of entomophthoromycosis.
Rhinoentomophthoromycosis caused by Conidiobolus sp commonly presents as a chronic granulomatous lesion that affects the rhinofacial subcutaneous tissue. We present an 18-year-old girl who presented with progressive bilateral proptosis and loss of vision since 2 weeks. Biopsy and fungal cultures confirmed diagnosis of Conidiobolus sp infection of the paranasal sinuses bilaterally with orbital extension and blindness. The clinical picture was complicated by the presence of sputum-positive cavitatory pulmonary tuberculosis, which was diagnosed at the same time. To our knowledge, this is the first such case to be reported from India. We also discuss the management of entomophthoromycosis. Despite many reports of success, there remains no consensus on the treatment of Conidiobolus infections of the nose and the paranasal sinuses with antifungal agents.


Public attitudes towards people who stutter in South Egypt.
Stuttering is a multifactorial speech disorder with significant social and psychological consequences. There is a lack of knowledge about public attitudes towards people who stutter (PWS) and the factors that can determine such attitudes in underprivileged communities. This study aimed to assess the public attitudes in South Egypt towards PWS and compare our results with those stored in a reference database representing 180 different samples. A multi-stage random sampling approach was used to recruit 650 people from Beni-Suef City in South Egypt. All participants were interviewed using the Arabic version of the Public Opinion Survey of Human Attributes-Stuttering (POSHA-S) after getting their informed consent. This instrument assesses people's Beliefs and Self Reactions towards PWS in addition to their sociodemographic characteristics. The Beliefs and Self Reactions subscores in addition to the Overall Stuttering Score of the Egyptian sample were remarkably lower than the median values of the reference database (12 versus 34), (-4 versus 2), and (4 versus 18), respectively. TV, radio, and films were the main sources of knowledge about stuttering. Egyptian participants who reported average to high income were more likely to have a positive attitude (≥50% of Overall Stuttering Score) towards PWS than their counterparts with low income (Odds Ratio = 1.57, 95% Confidence Interval: 1.08-2.28). People in South Egypt showed a less positive attitude towards PWS compared with other populations worldwide. Further studies should focus on changing the public attitudes towards PWS through awareness programs that consider the cultural perspectives of the society.


A machine learning framework for the evaluation of myocardial rotation in patients with noncompaction cardiomyopathy.
Noncompaction cardiomyopathy (NCC) is considered a genetic cardiomyopathy with unknown pathophysiological mechanisms. We propose to evaluate echocardiographic predictors for rigid body rotation (RBR) in NCC using a machine learning (ML) based model. Forty-nine outpatients with NCC diagnosis by echocardiography and magnetic resonance imaging (21 men, 42.8±14.8 years) were included. A comprehensive echocardiogram was performed. The layer-specific strain was analyzed from the apical two-, three, four-chamber views, short axis, and focused right ventricle views using 2D echocardiography (2DE) software. RBR was present in 44.9% of patients, and this group presented increased LV mass indexed (118±43.4 vs. 94.1±27.1g/m2, P = 0.034), LV end-diastolic and end-systolic volumes (P< 0.001), E/e' (12.2±8.68 vs. 7.69±3.13, P = 0.034), and decreased LV ejection fraction (40.7±8.71 vs. 58.9±8.76%, P < 0.001) when compared to patients without RBR. Also, patients with RBR presented a significant decrease of global longitudinal, radial, and circumferential strain. When ML model based on a random forest algorithm and a neural network model was applied, it found that twist, NC/C, torsion, LV ejection fraction, and diastolic dysfunction are the strongest predictors to RBR with accuracy, sensitivity, specificity, area under the curve of 0.93, 0.99, 0.80, and 0.88, respectively. In this study, a random forest algorithm was capable of selecting the best echocardiographic predictors to RBR pattern in NCC patients, which was consistent with worse systolic, diastolic, and myocardium deformation indices. Prospective studies are warranted to evaluate the role of this tool for NCC risk stratification.


Applying work-role attachment theory to retirement decision-making.
This study examined the relationships between work-role attachment variables (job involvement, affective organizational commitment, and career identification) and intention to retire. Results indicated that organizational commitment was negatively related to retirement intent. Contrary to expectations, job involvement displayed a positive relationship and career identification had no relationship to retirement intent.


Angiogenic monocytes: another colorful blow to endothelial progenitors.
This Commentary provides perspective on a related article by Sun-Jin Kim and coworkers (Am J Pathol: 172 AJP08-0819), who assess the contribution of bone marrow-derived cells to tumor angiogenesis in a physiologic, non-myeloablative setting and conclude that the actual angiogenic cell type incorporated in the newly formed vessels is actually monocytes/macrophages.


Asian Americans' adherence to Asian values, attributions about depression, and coping strategies.
Using Brickman et al.'s (1982) theoretical framework of responsibility attributions, the authors examined the relationships among adherence to Asian values, attributions about the cause of and solution to depression, and preferred coping strategies in a nonclinical sample of Asian Americans. Results of a path analysis (N = 238) indicate that attribution of cause fully mediated the relations between adherence to Asian values and use of coping strategies. Adherence to Asian values was positively related to attributing the cause of depression to internal factors, which was in turn associated with greater use of disengagement coping strategies and decreased use of engagement coping strategies. In addition, an internal attribution for the solution to depressive symptoms was related to more reliance on engagement coping strategies and a lower use of disengagement coping strategies. Practical implications of the results are discussed.


Clinical features and treatment outcome in Japanese patients with social anxiety disorder: chart review study.
The lifetime prevalence of social anxiety disorder (SAD) is high at 3-13%, but there have been only limited reports investigating the clinical features of this disorder in a large number of Japanese patients. The authors have conducted a retrospective, chart review study of 52 patients with SAD and obtained the following results. (i) The proportion of SAD in first visit outpatients at the Department of Psychiatry, Niigata University Medical and Dental Hospital, Niigata, Japan, was 1.04%. The male : female ratio was 1:0.73, so male patients appeared to be more common in the sample. (ii) With regard to subtype, generalized type (73% of the patients) was more common than non-generalized type (27%). (iii) The mean age of onset was 18.6 +/- 7.8 years, and there was a trend towards onset of disease at a younger age in the generalized type compared to the non-generalized type. (iv) The most common chief complaint was anxiety and tension in front of others (40.4%). (v) Pharmacotherapy resulted in improvement in 63.5% of the patients. Treatment by fluvoxamine and alprazolam resulted in high response rates of more than 70%.


Correlation of expression of aberrant immunophenotypic markers in T-ALL with its morphology: A pilot study.
Aberrant expression of immunophenotypic markers is commonly found in patients of acute leukemia. T-ALL also shows aberrant markers such as CD13, CD33, CD117, CD10, and CD79a. Morphologically, T-ALL has been categorized into L1, L2, and L3 subtypes. Till now, no study has been done to correlate these markers with morphological features of T-ALL. This study aimed to correlate the expression of aberrant immunophenotypic markers with morphology in T-ALL. All the cases of T-ALL diagnosed by flow cytometry over a period of 2½ year were taken out from the records of Hematology Section of Department of Pathology of University College of Medical Science and Guru Teg Bahadur Hospital and Max Hospital, Saket. Their peripheral blood smear was screened to correlate the morphology of blasts with the expression of aberrant markers. A total of 40 cases of T-ALL were identified during 2½ year period of our study. Morphological correlation was available for 23 cases. Aberrant expression of CD10 was present in 6 (35.3%) cases, CD79a in 9 (47.36%) cases, CD117 in 5 (42.28%) cases and myeloid antigen CD33 in 5 (38.46%) cases. CD117 and CD33-positive cases showed L2 morphology with the presence of convolutions, while cases with expression of CD79a had L1 morphology with absent-slight convolutions. CD10-positive cases had L1/L2 morphology with absent occasionally present convolutions. There seems to be an association of aberrant markers with L1 and L2 morphology. However, this needs to be tested for statistical significance on a larger sample size.


Obesity surgery and Ehlers-Danlos syndrome: challenges and considerations based on a case report.
Ehlers-Danlos syndrome is a hereditary connective tissue disorder that has gastrointestinal manifestations in over 50% of its cases. We present the first case of bariatric surgery in a patient with Ehlers-Danlos syndrome and outline management challenges in the context of the relevant literature. A 56-year-old man with type IV Ehlers-Danlos syndrome and a body mass index of 41.8 kg/m2 was referred to the bariatric centre of the Churchill Hospital, Oxford, for consideration of surgery for morbid obesity. His comorbidity included type 2 diabetes, hypertension, dyslipidaemia and obstructive sleep apnoea. He underwent a laparoscopic Roux-en-Y gastric bypass. His initial recovery was uneventful and he was discharged on the first postoperative day. Six weeks later, he presented with 43.9% excess weight loss and improved glycaemic control. Three months postoperatively, however, he complained of dysphagia, regurgitation and postprandial pain. A barium meal and gastroscopy suggested the presence of a gastric diverticulum. A surgical exploration was planned. Intraoperative gastroscopy demonstrated an asymmetrical gastric pouch dilatation and the pouch was therefore refashioned laparoscopically. Despite the initial symptomatic relief, two months later he experienced retrosternal pain with progressive dysphagia. Since then, multiple endoscopic dilatations of the gastro-oesophageal junction have been performed for recurrence of symptoms. Finally, a laparoscopic hiatus hernia repair and adhesiolysis was performed resulting in complete relief of patient's symptoms. Bariatric management of patients with Ehlers-Danlos syndrome can prove challenging. The bariatric team must implement a careful management plan including a detailed consent process, a tailored surgical intervention and a follow-up focused on potential gastrointestinal manifestations.


Oxidation and reduction of leghemoglobin in root nodules of leguminous plants.
Reactions involving changes that affect the function of leghemoglobin (Lb) are reviewed. The chemical nature of Lb and conditions inside nodules, such as slightly acid pH and the presence of metal ions, chelators, and toxic metabolites (nitrite, superoxide radical, peroxides), are conducive for oxidation of ferrous Lb (Lb(2+)) or its oxygenated form (LbO(2)) to nonfunctional ferric Lb (Lb(3+)) and ferryl Lb. Because Lb(3+) is nearly nonexistent in nodules and undergoes observable reduction in vivo, mechanisms must operate in nodules to maintain Lb in the Lb(2+) state. Redox reactions of Lb are mediated, for the most part, by activated oxygen species: (a) oxidation of LbO(2) to Lb(3+) involves superoxide; (b) excess peroxide oxidizes LbO(2) and Lb(3+) to ferryl Lb and may cause breakdown of heme, release of iron, and generation of hydroxyl radicals (protein radicals may be formed in this process); (c) enzymatic reduction of Lb(3+) requires active flavin and thiol groups and involves formation of peroxide; and (d) direct reduction of Lb(3+) by NADH is mediated by superoxide and peroxide. Transition metal ions and certain small molecules of nodules such as flavins may act as intermediate electron carriers between NADH and Lb(3+), increasing the rate of reaction, which then proceeds via superoxide or flavin radicals, respectively.


PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells.
Initiation of DNA replication in eukaryotes is dependent on the activity of protein phosphatase 2A (PP2A), but specific phosphoprotein substrates pertinent to this requirement have not been identified. A novel regulatory subunit of PP2A, termed PR48, was identified by a yeast two-hybrid screen of a human placental cDNA library, using human Cdc6, an essential component of prereplicative complexes, as bait. PR48 binds specifically to an amino-terminal segment of Cdc6 and forms functional holoenzyme complexes with A and C subunits of PP2A. PR48 localizes to the nucleus of mammalian cells, and its forced overexpression perturbs cell cycle progression, causing a G(1) arrest. These results suggest that dephosphorylation of Cdc6 by PP2A, mediated by a specific interaction with PR48, is a regulatory event controlling initiation of DNA replication in mammalian cells.


Differences between ion binding to eag and HERG voltage sensors contribute to differential regulation of activation and deactivation gating.
HERG (KCNH2) and ether-à-go-go (eag) (KCNH1) are members of the same subfamily of voltage-gated K+ channels. In eag, voltage-dependent activation is significantly slowed by extracellular divalent cations. To exert this effect, ions bind to a site located between transmembrane segments S2 and S3 in the voltage sensor domain where they interact with acidic residues that are conserved only among members of the eag subfamily. In HERG channels, extracellular divalent ions significantly accelerate deactivation. To investigate the ionbinding site in HERG, acidic residues in S2 and S3 were neutralized singly or in pairs to alanine, and the functional effects of extracellular Mg(2+) were characterized in Xenopus oocytes. To modulate deactivation kinetics in HERG, divalent cations interact with eag subfamily-specific acidic residues (D460 and D509) and also with an acidic residue in S2 (D456) that is widely conserved in the voltage-gated channel superfamily. In contrast, the analogous widely-conserved residue does not contribute to the ion-binding site that modulates activation kinetics in eag. We propose that structural differences between the ion-binding sites in the eag and HERG voltage sensors contribute to the differential regulation of activation and deactivation gating in these channels. A previously proposed model for S4 conformational changes during voltagedependent activation can account for the differential regulation of gating seen in eag and HERG.


Clinician Knowledge of Incontinence-Associated Dermatitis: A Multisite Survey of Healthcare Professionals in Acute and Subacute Settings.
This study examined clinicians' knowledge of incontinence-associated dermatitis (IAD) using the Barakat-Johnson Incontinence-Associated Dermatitis Knowledge Tool (Know-IAD). A cross-sectional multicenter survey. The setting was 6 hospitals across 5 health districts in New South Wales, Australia. The participants were nurses (registered nurses and enrolled nurses), physicians, allied health (occupational therapists, dietitians, and physiotherapists), and students (nursing and allied health). Data about IAD knowledge were collected from November 2019 to January 2020. The Know-IAD, an 18-item validated instrument that measures knowledge of IAD in 3 domains (etiology and risk, classification and diagnosis, and prevention and management), was administered to a cross section of eligible clinicians. The participants anonymously completed hard copy surveys. Descriptive and exploratory analyses were conducted to quantify clinicians' knowledge about the etiology and risk, classification and diagnosis, and prevention and management of IAD. A mean knowledge score of 70% was considered to be satisfactory. Four hundred twelve respondents completed the survey. One hundred twenty nine respondents (31.3%) achieved 70% correct responses and greater for the entire set of items. For the etiology and risk domain, 348 respondents (84.5%) obtained a score of 70% correct responses and greater, 67 respondents (16.3%) achieved 70% correct responses and greater for the classification and diagnosis domain, and 84 respondents (20.4%) achieved 70% correct responses and greater for the prevention and management domain. Clinicians tend to have low knowledge and recognition of IAD, particularly in the areas of classification and diagnosis along with prevention and management. They tend to have higher knowledge of how IAD is caused and the risk factors. This study has identified knowledge gaps for further education that can improve assessment, prevention, and management of IAD.


Self-healing graphene-based composites with sensing capabilities.
A self-healing composite is fabricated by confining a supramolecular polymer in a graphene network. The network provides electrical conductivity. Upon damage, the polymer is released and flows to reform the material. Healing is repeatable and autonomous. The composite is sensitive to pressure and flexion and recovers its mechanical and electrical properties even when rejoining cut surfaces after long exposure times.


The Influence of Entrepreneurs' Online Popularity and Interaction Behaviors on Individual Investors' Psychological Perception: Evidence From the Peer-To-Peer Lending Market.
Inappropriate social interactions of entrepreneurs can generate negative effects in the peer-to-peer lending market. To address this problem and assist peer-to-peer entrepreneurs in customizing their online interaction strategies, we used the cutting-edge cognitive-experiential self-system conceptual model and studied the relationship between peer-to-peer entrepreneurs' interactions and financing levels. Online interactive information was categorized as emotional or cognitive, adding the moderator of entrepreneur popularity, and the effect of these interactions on individual investors was analyzed. We found that the entrepreneurs' online interactive information affected psychological perception of entrepreneurs and their corresponding brand image. The interaction between popularity and interactive information types was significant. The findings imply that less popular entrepreneurs should engage in emotional interactions, while more popular entrepreneurs should choose cognitive interactions. Online interaction created comparative advantages in the financing activities of peer-to-peer companies. These results expand understanding of the psychological facets of the consumer-brand relationship in the digital world, and extend the current literature. This study also highlights key areas of learning and application for both practitioners and scholars of organizational psychology.


Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis.
Stem Leydig cells (SLCs), precursors of testicular Leydig cells that secrete testosterone required for male sexual differentiation, spermatogenesis, and fertility, were recently identified in rat testes. Various types of stem cells have shown the ability to differentiate into other tissues, but there is no information on the plasticity of adult rat SLCs (rSLCs). This study investigated the ability of rSLCs to transdifferentiate into cell types from all three germ layers-prostatic epithelium (endoderm), uterine epithelium (mesoderm), and epidermis (ectoderm)-under the influence of inductive mesenchyme from fetal and neonatal tissues. To differentiate rSLCs into cells of other lineages, mesenchyme from green fluorescent protein (GFP)-expressing mice was used. Tissue recombinants of urogenital sinus mesenchyme (a potent prostate inducer) and rSLCs grafted into adult male hosts formed ductal structures resembling prostate after 5 weeks. Prostate epithelium was of rSLC origin as determined by absence of GFP expression, and expressed characteristic markers of prostatic epithelium. Similarly, uterine mesenchyme + rSLCs tissue recombinants contained a simple columnar epithelium that was histologically similar to normal uterine epithelium and expressed typical uterine epithelial markers, but was of rSLC origin. In contrast, epidermal tissue was absent in fetal dermis + rSLCs recombinants, suggesting rSLCs did not form skin epithelium. Thus, rSLCs can transdifferentiate into uterine and prostatic epithelium, mesodermal, and endodermal derivatives, respectively, but they may have a limited transdifferentiation potential, as shown by their inability to form epidermis, an ectodermal derivative.


Lithotripter outcomes in a community practice setting: comparison of an electromagnetic and an electrohydraulic lithotripter.
We assessed patient outcomes using 2 widely different contemporary lithotripters. We performed a consecutive case series study of 355 patients in a large private practice group using a Modulith® SLX electromagnetic lithotripter in 200 patients and a LithoGold LG-380 electrohydraulic lithotripter (TRT, Woodstock, Georgia) in 155. Patients were followed at approximately 2 weeks. All preoperative and postoperative films were reviewed blindly by a dedicated genitourinary radiologist. The stone-free rate was defined as no residual fragments remaining after a single session of shock wave lithotripsy without an ancillary procedure. Patients with multiple stones were excluded from analysis, leaving 76 and 142 treated with electrohydraulic and electromagnetic lithotripsy, respectively. The stone-free rate was similar for the electrohydraulic and electromagnetic lithotripters (29 of 76 patients or 38.2% and 69 of 142 or 48.6%, p = 0.15) with no difference in the stone-free outcome for renal stones (20 of 45 or 44.4% and 33 of 66 or 50%, p = 0.70) or ureteral stones (9 of 31 or 29% and 36 of 76 or 47.4%, respectively, p = 0.08). The percent of stones that did not break was similar for the electrohydraulic and electromagnetic devices (10 of 76 patients or 13.2% and 23 of 142 or 16.2%) and ureteroscopy was the most common ancillary procedure (18 of 22 or 81.8% and 30 of 40 or 75%, respectively). The overall mean number of procedures performed in patients in the 2 groups was similar (1.7 and 1.5, respectively). We present lithotripsy outcomes in the setting of a suburban urology practice. Stone-free rates were modest using shock wave lithotripsy alone but access to ureteroscopy provided satisfactory outcomes overall. Although the acoustic characteristics of the electrohydraulic and electromagnetic lithotripters differ substantially, outcomes with these 2 machines were similar.


Staged exchange arthroplasty for shoulder sepsis.
Eight patients with shoulder sepsis were treated with staged exchange arthroplasty using antibiotic-impregnated polymethyl methacrylate spacers shaped and fitted to the patient's anatomy after extensive joint débridement. Intravenous antibiotic therapy followed for a minimum of 3 months. At the end of 6 months, the patients were evaluated for any clinical or laboratory signs of infection; none were encountered. Exchange prosthetic reconstructions were performed using standard implants fixed with antibiotic-impregnated polymethyl methacrylate cement. Three patients underwent a revision to total shoulder arthroplasty, whereas 5 underwent hemiarthroplasty of the humerus with local capsular flap covering of the glenoid. All patients experienced substantial pain relief and improvement in function despite limited total overhead motion, showing this technique to be a satisfactory salvage procedure for managing sepsis of the glenohumeral joint primarily and after total shoulder arthroplasty.


Regeneration of dendritic cells in aged mice.
Age-related thymic involution causes a decreased output of thymocytes from the thymus, thereby resulting in impairment of T cell-mediated immunity. While alterations in the T cell and non-haematopoietic stromal compartments have been described, the effects of thymic involution on thymic dendritic cells (DC) are not clearly known. Thymic DC play an essential role in shaping T cell-mediated immune responses by deleting self-reactive thymocytes to establish central tolerance and by inducing regulatory T-cell (Treg) development. It is therefore important to assess the prevalence of and alterations to thymic DC with age, as this may impact on their function. We assessed the numbers and proportions of the three distinct subsets of thymic DC in ageing mice, and showed that these subsets are differentially regulated. This is expected as thymic DC subsets have different origins of development. We further assessed the responses of thymic DC in a regenerative environment, such as that induced by sex-steroid ablation (SSA), and clearly showed that, consistent with global thymus regrowth, all three DC populations increased in numbers and regained their relative proportions to thymocytes after an initial lag period. These findings are important for the clinical translation of thymic regenerative approaches, and indicate that SSA facilitates the maintenance of critical processes such as negative selection and Treg induction through promoting thymic DC regeneration.


Modulatory effect of subthalamic nucleus on the development of fatigue during exhausting exercise: an in vivo electrophysiological and microdialysis study in rats.
The purpose of the study was to investigate the modulatory effect of changes of subthalamic nucleus (STN) activity on the development of central fatigue during exhausting exercise, and reveal the possible mechanism that might affect STN activity from the perspective of neurotransmitters. Rats were randomly divided into electrophysiology and microdialysis study groups. For electrophysiological study, electrical activity in sensorimotor cortex and STN were simultaneously recorded before, during and 90min after the exhausting exercise. For microdialysis study, extracellular fluid of STN was continuously collected with a microdialysis probe and glutamate (Glu), gamma-aminobutyric acid (GABA) levels were subsequently detected with high performance liquid chromatography (HPLC). The behavioral studies showed that rats ran well initiatively with the treadmill exercise in the beginning, 45 ± 11.5min later, movement capacity reduced obviously (which was termed as 'early fatigue'). Correspondingly, STN activity increased significantly compared with rest condition (p < 0.05), while, cortex activity decreased significantly (p < 0.05). Subsequently, rats continued their exercise with minor external stimulation till exhaustion. Cortex activity reached the minimum value under exhaustion condition, while STN activity changed insignificantly (p > 0.05). For microdialysis study, the dynamic change of Glu/GABA ratio was consistent with the change of STN activity during the development of 'early fatigue' rather than the development of exhaustion. In conclusion, the present study shows that, the development of the cortex fatigue during exhausting exercise consists of two phases, 'early fatigue' and exhaustion. Our results suggest that, dynamic changes of STN activity are closely relevant to the development of 'early fatigue' rather than exhaustion, and the changes of STN activity during the development of 'early fatigue' might be partly related to the variance of Glu and GABA levels in STN extracellular fluid. Key pointsThe development of the cortex fatigue during exhausting exercise consists of two phases, 'early fatigue' and exhaustion.Dynamic changes of STN activity are closely relevant to the development of 'early fatigue' rather than exhaustion.The changes of STN activity during the development of 'early fatigue' might be partly related to the variance of Glu and GABA levels in STN extracellular fluid.


Mono-Dendronized β-Cyclodextrin Derivatives as Multitasking Containers for Curcumin. Impacting Its Solubility, Loading, and Tautomeric Form.
In this study, three mono-dendronized β-cyclodextrin (βCD) derivatives (βCD-1G, βCD-2G, and βCD-3G) were used as multitasking containers of curcumin (CUR) to influence its aqueous solubility and tautomerism, both of which are related to its biological activity. We evaluated the relevant physicochemical properties of these containers associated with their potential hosting capacity. All mono-dendronized derivatives exhibited enhanced solubility in different solvents, including water, in comparison with native βCD. Gas-phase geometry optimizations by density functional theory (DFT) confirmed that none of the dendrons blocked the passage of CUR into the βCD cavity, and depending on the generation, different preorganization scenarios were promoted before complexation. Phase solubility diagrams showed that all the dendronized containers have superior performance for solubilizing CUR compared to native βCD. We proved that coprecipitation is most efficient than lyophilization for forming inclusion complexes (ICs) with dendronized containers. Even though βCD-3G with the largest 3G dendron exhibited the highest CUR loading, the complexation of CUR with βCD-2G provided the supramolecular system that contains CUR preferentially in its diketo tautomer, which is known for its antioxidant activity.