Involvement of peripheral prostaglandins in formalin-induced nociceptive behaviours in the orofacial area of rats.
Prostaglandins (PGs) are known to be involved in the pathogenesis of inflammation and pain. However, their role in orofacial pain is not clearly understood. The present study was undertaken to determine the effect of systemic and locally administered nonsteroidal anti-inflammatory drugs (NSAIDs) on the role of PGs in orofacial pain induced by formalin in rats. The subcutaneous injection of formalin into the rat upper lip generated behavioural responses that lasted for several minutes. The orofacial responses due to formalin were seen in two distinct phases, the early response (0-3 min) and the continuous prolonged response (9-45 min). Systemic administration of ketorolac or diclofenac (10 and 30 mg/kg, i.p.) significantly attenuated formalin-induced nociceptive behaviour in the phase-2, but not in the phase-1 of the formalin test. Similarly, subcutaneous (local) administration of ketorolac or diclofenac in the orofacial area (100 and 300 microg/lip) markedly decreased the phase-2 nociceptive response due to formalin. However, both the drugs had no effect on the phase-1 response of the formalin test. These results suggest that PGs, particularly peripheral PGs are involved in nociceptive behaviour following formalin injection in the orofacial area.


Desorption electrospray ionization and matrix-assisted laser desorption/ionization as imaging approaches for biological samples analysis.
The imaging of biological tissues can offer valuable information about the sample composition, which improves the understanding of analyte distribution in such complex samples. Different approaches using mass spectrometry imaging (MSI), also known as imaging mass spectrometry (IMS), enabled the visualization of the distribution of numerous metabolites, drugs, lipids, and glycans in biological samples. The high sensitivity and multiple analyte evaluation/visualization in a single sample provided by MSI methods lead to various advantages and overcome drawbacks of classical microscopy techniques. In this context, the application of MSI methods, such as desorption electrospray ionization-MSI (DESI-MSI) and matrix-assisted laser desorption/ionization-MSI (MALDI-MSI), has significantly contributed to this field. This review discusses the evaluation of exogenous and endogenous molecules in biological samples using DESI and MALDI imaging. It offers rare technical insights not commonly found in the literature (scanning speed and geometric parameters), making it a comprehensive guide for applying these techniques step-by-step. Furthermore, we provide an in-depth discussion of recent research findings on using these methods to study biological tissues.


Quercetin preferentially induces apoptosis in KRAS-mutant colorectal cancer cells via JNK signaling pathways.
Colorectal cancer (CRC) is the third most common type of cancer, and its incidence and mortality are markedly increasing worldwide. Oncogenic mutations of KRAS occur in up to 40% of CRC cases and pose a great challenge in the treatment of the disease. Quercetin is a dietary flavonoid that exerts anti-oxidant, anti-inflammatory, and anti-cancer properties. The current study investigated the anti-proliferative effect of quercetin on CRC cells harboring mutant or wild-type KRAS. The effect of quercetin on cell viability was investigated by MTT and colony formation assays, and apoptosis was detected using flow cytometry by labeling cells with Annexin V-FITC. The expression of the relevant proteins was examined by Western blotting. The data revealed that KRAS-mutant cells were more sensitive to quercetin-induced apoptosis than wild-type cells. Caspase activation was involved in quercetin-induced apoptosis. In addition, quercetin selectively activated the c-Jun N-terminal kinase (JNK) pathway in KRAS-mutant cells, while inhibition of phospho-JNK by SP600125 blocked quercetin-induced apoptosis. The results of the present study suggest that treatment with quercetin, a common flavonoid in plants, is potentially a useful strategy for the treatment of CRCs carrying KRAS mutations.


Toxicological potential of Aloysia gratissima: Insights from chemical analysis and in vitro studies.
Aloysia gratissima leaves are popularly used to treat respiratory, digestive, and nervous system disorders. Several studies have been carried out to determine the biological activity of A. gratissima, such as its antibacterial and anti-edematogenic activities, but despite the beneficial uses of A. gratissima, few studies have examined the toxicological profile of this plant. This study aimed to determine the chemical composition, cytotoxic, genotoxic, mutagenic potential, and antioxidant activity of an aqueous extract of A. gratissima leaves (AG-AEL). The phytochemical constitution of AG-AEL was assessed by colorimetric analyses and High-performance liquid chromatography (HPLC). The inorganic elements were detected by Particle-Induced X-ray Emission (PIXE). The antioxidant, cytotoxicity, genotoxic, and mutagenic activities were evaluated in vitro by Di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH), Sulforhodamine B (SRB) assay, comet assay, and Salmonella/microsome assays. AG-AEL indicated the presence of terpenoids, flavonoids, and phenolic acids. HPLC detected rutin at 2.41 ± 0.33 mg/100 mg. PIXE analysis indicated the presence of Mg, Si, P, S, K, Ca, Mn, and Zn. The 50% inhibitory concentration was 84.17 ± 3.17 μg/mL in the DPPH assay. Genotoxic effects were observed using the Comet assay in neuroblastoma (SH-SY5Y) cells and mutations were observed in TA102 and TA97a strains. The extract showed cytotoxic activities against ovarian (OVCAR-3), glioblastoma (U87MG), and colon (HT-29) cancer cell lines. In conclusion, AG-AEL increased DNA damage, induced frameshift, and oxidative mutations, and showed cytotoxic activities against different cancer cells. The in vitro toxicological effects observed suggest that this plant preparation should be used with caution, despite its pharmacological potential.


Patchy hyperautofluorescence as a predictive factor for the recurrence of punctate inner choroidopathy.
To investigate baseline clinical and imaging factors that may correlate with risk of recurrence of punctate inner choroidopathy (PIC). In this retrospective observational study, charts and multimodal imaging of forty-five patients diagnosed with PIC during the active inflammatory phase were reviewed. MMI examinations, including fundus photography, shortwave fundus autofluorescence(SW-FAF), fluorescein angiography(FFA), indocyanine green angiography(ICGA), and spectral domain optical coherence tomography(SD-OCT_), were conducted to diagnose PIC, and MMI parameters at baseline were assessed as potential biomarkers indicating the recurrence of inflammation. Statistical analysis was performed to determine the clinical and imaging factors associated with recurrence of PIC. Among the 45 recruited patients, 18 (40 %) had at least one episode of recurrence during a mean follow-up period of 23.66 ± 12.65 months (range, 12-50 months). Best corrected visual acuity (BCVA) at the final visit during the follow-up was significantly different between the recurrence and nonrecurrence groups. Patchy hyperautofluorescence at baseline appeared in 77.78 % of the patients with recurrence, and the incidence of patchy hyperautofluorescence was significantly different between the patients with recurrence and those without recurrence (P<0.001). Recurrence is not rare among PIC patients and leads to a worse visual acuity outcome. Patchy hyperautofluorescence at baseline is a risk factor for recurrence of PIC. Patchy hyperautofluorescent areas in PIC patients may indicate a need for close follow-up even though PIC-related inflammation regresses.


Ca(2+)- and Na(+)-dependent depolarization induced by maitotoxin in the crayfish giant axon.
1. Maitotoxin (MTX) depolarized the membrane of the crayfish giant axon and decreased the amplitude and maximum rate of rise of action potentials in an irreversible manner. 2. The depolarizing action of MTX was attenuated in low Ca (1 mM; 1/10 of normal concentration) solution and was also inhibited by 2 mM Co2+, 300 microM Ni/+, 1 microM nifedipine, 10 microM verapamil or 1 microM tetrodotoxin. 3. These results suggest that the depolarization by MTX in the crayfish giant axon may be related to changes not only in Ca permeability but also in Na permeability, possibly through the modification of existing Na or Ca channels and/or a new type of channel or pore induced by MTX.


Under utilisation of the 2-week wait initiative for lung cancer by primary care and its effect on the urgent referral pathway.
The '2-week wait' scheme for referral of patients with cancer to secondary care coincided with the introduction of Department of Health (DoH) Guidelines on referral of patients with suspected lung cancer. The aim of this study was to examine the impact of this process on the urgent referral pathway for lung cancer. Medical records of all patients referred with suspected lung cancer were reviewed for the year prior to introduction of the 2-week wait and DoH guidelines and for the subsequent 24 months. A total of 1044 patients were referred, of which 650 (62%) were found to have malignancy. In the first and second years of the 2-week wait scheme, only 57 and 58% were referred via the scheme. Department of Health guidelines were followed in all but a small number. Median wait time increased from 7 to 9 days. The proportion of all urgent referrals seen within 2 weeks fell from 84 to 71%. The proportion of non-2-week wait urgent referrals being seen within 2 weeks was only 75.5% in the first year of the scheme and fell further to 60.9% in the second year. The absolute number of referrals rose and the proportion having cancer fell from 78% before the scheme to 46% in the second year. During this time, there was no change in stage at presentation. Symptoms were not helpful in discriminating benign from malignant disease and haemoptysis was actually more common in the benign group. However, over 50% of patients in the benign group were appropriate to be seen in secondary care. The 2-week wait scheme has so far failed to reduced waiting times for lung cancer. The findings of this study suggest that this is partly due to continued usage of urgent referral routes outside the 2-week wait scheme and secondly due to a large increase in referrals, probably generated by the introduction of the DoH guidelines. Some adjustment to the guidelines may be appropriate to reflect more emphasis on the early performance of a chest X-ray and the use of direct access to other imaging modalities such as CT. Patients referred outside the 2-week wait are disadvantaged and thus practitioners would be wise to refer all their patients through the 2-week wait system.


[The long road for psychiatric care in prisons].
From the 19th century to the present day, the history of psychiatry in prisons has evolved considerably. In parallel with successive laws, codes and articles, psychiatry has gained in structure. From the "medical prison", mental health consultations in every detention centre, the regional medico-psychological services, to today's specially equipped hospital units (UHSA), prisoners receive both preventive care as well as curative treatment.


Dorsal-to-Ventral Cortical Expansion Is Physically Primed by Ventral Streaming of Early Embryonic Preplate Neurons.
Despite recent studies elucidating the molecular mechanisms underlying cortical patterning and map formation, very little is known about how the embryonic pallium expands ventrally to form the future cortex and the nature of the underlying force-generating events. We find that neurons born at embryonic day 10 (E10) in the mouse dorsal pallium ventrally stream until E13, thereby superficially spreading the preplate, and then constitute the subplate from E14. From E11 to E12, the preplate neurons migrate, exerting pulling and pushing forces at the process and the soma, respectively. At E13, they are morphologically heterogeneous, with ∼40% possessing corticofugal axons, which are found to be in tension. Ablation of these E10-born neurons attenuates both deflection of radial glial fibers (by E13) and extension of the cortical plate (by E14), which should occur ventrally, and subsequently shrinks the postnatal neocortical map dorsally. Thus, the preplate stream physically primes neocortical expansion and arealization.


RPSA distribution and expression in tissues and immune cells of pathogen-infected mice.
40S ribosomal protein SA (RPSA), a component of the small ribosomal subunit, is a high-affinity receptor of laminin that is widely expressed in cells and involves in many biological processes. However, it hasn't been reported which tissues and cells may be targeted by RPSA-mediated pathogen regulation. Therefore, in this study, a gram-positive bacterium Streptococcus suis Type 2 (SS2), gram-negative bacterium Actinobacillus pleuropneumoniae (A.pleuropneumoniae), and porcine circovirus Type 2 (PCV2) were used to infect ICR mice. The effects of infection with the three pathogens on expression levels of RPSA in mouse tissues and peripheral blood immune cells were analysed by immunohistochemistry and flow cytometry. The results suggested that the pathological changes in mice infected with SS2 were mainly manifested as congestion and inflammatory infiltration in the meninges, lungs, hearts and livers. The mice infected with A.pleuropneumoniae or PCV2 showed lung lesions and mild hepatocyte degeneration, respectively. In uninfected mice, RPSA protein was expressed to various degrees in all tissues except the spleen. After SS2 infection for 3 d, the expression of RPSA in the liver and brain increased, while decreased significantly in the heart and duodenum. These results were corroborated on examining the correlation between RPSA expression and the process of SS2 infection, except that there was no significant difference between the expression levels in the heart at 1 d and 3 d. After A.pleuropneumoniae and PCV2 infection for 3 d, the expression of RPSA decreased in the heart, and brain, respectively. Additionally, under physiological conditions, RPSA expression in CD4+ T cells, CD8+ T cells, neutrophils, and macrophages in the peripheral blood of mice was higher than that in B cells and NK cells. After SS2 infection for 3 d, RPSA expression increased significantly in CD4+ T cells and CD8+ T cells but decreased significantly in macrophages. The expression of RPSA after A.pleuropneumoniae and PCV2 infection were similar, and RPSA expression decreased only in macrophages. The results revealed that RPSA showed different expression levels in tissues and immune cells due to different pathogens causing disease courses, suggesting different target tissues and target cells in RPSA-mediated pathogenesis after infection, which supports the systematic study of the pathogenesis of RPSA in infectious diseases.


Age-Related Changes in the System Metalloproteinases/Tissue Metalloproteinase Inhibitors and Proteoglycan Components in Mouse Organs.
Activity of MMP and content of TIMP and some proteoglycan components were measured in the liver, lungs, and spleen of BALB/c mice aging 2, 6, and 12 months. The increase in the content of proteoglycan components in mouse organs was associated with age-related changes in MMP activity and TIMP-1 and TIMP-2 levels. The ratio between MMP activity and content of TIMP-1 and TIMP-2 differed in the studied organs. The levels of TIMP-1 and TIMP-2 in mouse blood serum and their concentration in studied organs changed asynchronously with age. They are important regulators that determine MMP activity in the analyzed age periods in mice, which can be determined as periods of growth, development, and ageing.


An innovative next-generation endoscopic submucosal injection material with a 2-step injection system (with video).
Next-generation submucosal injection materials (SIMs) with higher performance and flexibility than the current SIMs (eg, 0.4% sodium hyaluronate solution [HA]) are expected to improve the outcomes of endoscopic submucosal dissection (ESD) but are difficult to develop. We developed a next-generation SIM by devising a 2-solution-type SIM comprising 2.0% calcium chloride solution (Ca) and 0.4% sodium alginate solution (SA) and evaluated its performance. Viscoelasticity, submucosal elevation height, and injection pressure of HA, SA, and the next-generation SIM were measured. Outcomes of ESDs on pseudo-lesions in ex vivo porcine stomach/colon models were compared. The dramatic increase in SA viscoelasticity with the addition of Ca facilitated the formation of highly viscous submucosal cushions that can be controlled by endoscopists. The submucosal elevation height of the next-generation SIM was significantly higher than that of HA or SA with the same injection pressure. The ESD procedure time using the next-generation SIM was significantly shorter than that using HA or SA (14.2 ± 6.1 vs 29.2 ± 9.1 minutes, P = .0004, or 14.2 ± 6.1 vs 29.1 ± 5.9 minutes, P <.0001). Furthermore, the total injection volume for the next-generation SIM was considerably lower than that for HA or SA (7.0 ± 0.9 vs 17.2 ± 3.4 mL, P <.0001, or 7.0 ± 0.9 vs 16.2 ± 2.9 mL, P <.0001). We developed an ideal next-generation SIM that achieved high performance and high flexibility in ex vivo models. Our findings warrant further investigations in a patient population.


Fragments of illness: The Death of a Beekeeper as a literary case study of cancer.
The first decisive steps of medicine towards becoming a science in its present shape happen to coincide with "the rise of the novel" in the eighteenth century. Before this well known and in our days still growing scientific specialization of medicine, the connections between literature and medicine were both many and close. By reading and analyzing a contemporary novel, The Death of a Beekeeper by the Swedish author Lars Gustafsson (1978), this article is an attempt to explore to which extent a fictional narrative about a unique case of cancer may illuminate challenges associated with the experience of serious illness. Our claim is that medicine might draw wisdom from literature, its ability to create connections through narrative, to illuminate the complexity of ethical dilemmas, and to intertwine symptoms, life stories, and contexts. We argue that by being in the company of literary narratives and philosophical questions, physicians as well as other health care professionals may acquire clinically relevant skills which help them reach the ethically defined goals of their profession.


Donor oocyte pregnancy with transfer of deep-frozen embryo.
An infertile woman suffering from premature menopause conceived on her eighth attempt of ET following the transfer of a single frozen-thawed embryo, the ovum being donated anonymously by a patient undergoing tubal sterilization.


Cytological and proteomic evidence reveals the involvement of mitochondria in hypoxia-induced quality degradation in postharvest citrus fruit.
Hypoxia frequently occurs in postharvest logistics, which greatly influences fruit storability. Here, we for the first time studied the dynamic variations of mitochondrial morphology in living citrus fruit cells, and revealed that waxing treatment-induced hypoxia strongly triggered mitochondrial fission and fragmentation. Correspondingly, hypoxia caused a decline in mitochondrial membrane potential and mobility. Besides, impairment of energetic and redox status was also found in waxed fruit. The proteomic changes of mitochondria after waxing treatment were also characterized. Using weighted gene co-expression network analysis (WGCNA), we identified 167 key hypoxia-responsive proteins, which were mainly involved in fatty acid, amino acid and organic acid metabolism. Metabolite analysis verified that waxing treatment promoted the accumulation of several hypoxic metabolites, such as ethanol, acetaldehyde, succinic acid and γ-aminobutyric acid (GABA). Taken together, our findings provide new insights into the cytological and proteomic responses of mitochondria to hypoxia during fruit storage.


Physician adherence to clinical guidelines in euthanasia and assisted suicide in the Netherlands: a qualitative study.
Euthanasia and assisted suicide laws in the Netherlands require physicians meet clinical guidelines when performing the practice to ensure death is peaceful and painless. Despite oversight by the regional review committees over each case, little research exists into the frequency of guideline deviation and the reasons for nonadherence. Cases reported and reviewed between 2012 and 2017 that did not meet due medical care were analysed for thematic content. Semistructured interviews were conducted with 11 Dutch physicians on their experience with the clinical and pharmacological elements of euthanasia and assisted suicide, their interaction and comportment with the recommended guidelines, and reasons why guideline deviation might occur. Reported case reviews and interviews were used to obtain themes and subthemes to understand how and why deviations from clinical guidelines happened. Violations of due medical care were found in 42 (0.07%) of reported cases. The regional review committees found physicians in violation of due medical care mostly for inadequate confirmation of coma-induction and deviations from recommended drug dosages. Physicians reported that they rarely deviated from the guidelines, with the most common reasons being concern for the patient's family, concern over the drug efficacy, mistrust in the provided guidelines, or relying on the poor advice of pharmacists or hospital administrators. Deviations from the guidelines and violations of due medical care are rare, but should nonetheless be monitored and prevented. A few areas for improvement include skills training for physicians, consistency between review committee rulings, and further clarity on dosage recommendations.


Hamstring Braid Graft Technique for Anterior Cruciate Ligament Reconstruction.
Hamstring autograft is one of the most used grafts for anterior cruciate ligament (ACL) reconstruction, although there are several graft preparation techniques. It is extremely difficult to mimic the biomechanical properties of the native ACL; thus, it is important to achieve a proper graft configuration, diameter, and length. To avoid reruptures, an optimal and reproducible hamstring autograft is desired. Hamstring autograft has been traditionally devalued when compared with other options such as bone-patellar tendon-bone autograft. The purpose of this Technical Note is to describe in detail a hamstring braid graft configuration that could potentially overcome the past disadvantages of ACL reconstruction.


Immunomodulatory effect of imidacloprid on macrophage RAW 264.7 cells.
The neonicotinoid imidacloprid was promoted in the market because of widespread resistance to other insecticides, plus its low mammalian impact and higher specific toxicity towards insects. This study aimed to evaluate the immunomodulatory effect of imidacloprid on macrophages. RAW 264.7 cells were incubated to 0-4000 mg/L of imidacloprid for 24 and 96 h. Imidacloprid presented a concentration-dependent cytotoxicity after 24 h and 96 h incubation for MTT reduction (3-(4,5-dimethyl-thiazol-2-yl)- 2,5-diphenyltetrazolium bromide) (EC50 519.6 and 324.6 mg/L, respectively) and Neutral Red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) assays (EC50 1139.0 and 324.2 mg/L, respectively). Moreover, imidacloprid decreased the cells' inflammatory response and promoted a mitochondrial depolarization. The complex II and succinate dehydrogenase (SDH) activities in RAW 264.7 cells incubated with imidacloprid increased more at 24 h. These results suggest that imidacloprid exerts an immunomodulatory effect and mitochondria can act as regulator of innate immune responses in the cytotoxicity mediated by the insecticide in RAW 264.7 cells.


Decline of ambient air pollution levels due to measures to control automobile emissions and effects on the prevalence of respiratory and allergic disorders among children in Japan.
In Japan, air pollution due to nitrogen oxides (NOx) and particulate matter (PM) has been gradually reduced since control measures based on the Automobile NOx/PM law were enforced beginning in 2001. The effects of decrease in air pollutants due to the control measures during the past decade on the prevalence of respiratory and allergic disorders such as asthma in children were evaluated. Using data of 618,973 children collected in 28 regions of Japan from 1997 to 2009, we evaluated whether reductions in the concentrations of nitrogen dioxide (NO2) and suspended particulate matter (SPM) contribute to the decrease in the prevalence of asthma, wheezing, bronchitis, allergic rhinitis, and atopic dermatitis by multiple linear regression analysis, including adjustments for related factors. The annual rates of decrease in air pollution in the PM-law-enforced areas were 2.0 and 2.5 times higher for NO2 and SPM, respectively, compared with those in the non-enforced areas. The prevalence of asthma decreased significantly at -0.073% per year in the areas in which measures based on the Automobile NOx/PM law were taken but not in area where such measures were not applied. Multiple linear regression analysis showed a reduction in the ambient air pollution was significantly associated with a reduction in the prevalence of asthma, with a rate of 0.118% [95% confidence interval (CI): 0.012-0.225] per 1 ppb for NO2, and 0.050% [95% CI: 0.020-0.080] per 1 μg/m(3) for SPM. An increase in the ambient air pollution was associated with an increase in the prevalence of atopic dermatitis of 0.390% [95% CI: 0.107-0.673] per 1 ppb for NO2, 0.141% [95% CI: 0.058-0.224] per 1 μg/m(3) for SPM. The changes in the prevalence of wheezing and allergic rhinitis were not significantly correlated with changes in air pollutant concentrations. The enforcement of measures to control automobile emissions based on the Automobile NOx/PM law was shown to have reduced air pollution and contributed to decreases in the prevalence of respiratory and allergic disorders in 3-year-old children.


Parenting self-efficacy and empowerment among expectant mothers with substance use disorders.
to describe parenting self-efficacy and family empowerment among expectant mothers with substance use disorders. the study employed a quantitative cross-sectional design. participants were 71 pregnant women with substance use disorders entering a gender-specific, substance use disorder, residential treatment facility. measurement tools included: the demographic data form, the Parenting Sense of Competence Scale, the Addiction Severity Index, and the Family Empowerment Scale. women in their third trimester reported statistically significant higher levels of both parenting self-efficacy and family empowerment than women in their first trimester. interventions that promote parenting self-efficacy and family empowerment need to target women in their first trimester. midwives with specialized training in substance abuse disorders are in a unique position to bolster expectant mothers' parenting capabilities during the addiction recovery process.


Regulative effects of hawthorn leave flavonoids on cytotoxicity, NO and Ca2+ in hypoxia-treated human umbilical vein endothelial cells.
To evaluate the potential effect of HLF (Hawthorn leave flavonoids, w/w, 80% flavonoids) against thrombus formation, effect of HLF on hypoxia-treated human umbilical vein endothelial cell (HUVECs) was studied. The levels of cytotoxicity and NO upon HUVECs were studied by flow cytometry. Moreover, the level of calcium ion in HUVECs was examined through laser scanning confocal microscopy. Data from this study showed that HLF at concentrations of 5 micrograms/ml and 10 micrograms/ml decreased the cytotoxicity of hypoxia to HUVECs (P<0.05, P<0.01). The intracellular levels of NO and calcium ion were downregulated by HLF at concentrations of 5 micrograms/ml (P<0.01; P<0.01) and 10 micrograms/ml (vs control, P<0.01; P<0.01) too. Results observed suggest that HLF protect HUVECs from hypoxia partly through its regulative effect on NO and calcium ion levels.


SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer.
SLC25A22, a member of mitochondrial carrier system (MCS) family encoding a mitochondrial glutamate transporter, has been reported to have vital roles in promoting proliferation and migration in cancer. Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis. We aimed to determine the expression and function of SLC25A22 in GBC. Immunohistochemistry (IHC) staining analysis and quantitative real-time PCR (qRT-PCR) were conducted to determine the expression of SLC25A22 in GBC tissues. Human NOZ and GBC-SD cells were used to perform the experiments. The protein expression was detected by western-blot analysis. Cell viability was evaluated via CCK-8 assay and colony formation assay. Cell migration and invasion in vitro were investigated by wound healing and transwell assay. Annexin V/PI staining assay for apoptosis were measured by flow cytometry. The effect of SLC25A22 in vivo was conducted with subcutaneous xenograft. We indicated that the expression of SLC25A22 was significantly upregulated in GBC tumor tissues as well as cell lines. Downregulation of SLC25A22 inhibited GBC cell growth and proliferation in vitro and in vivo and also had an effect on metastasis of GBC cells through the EMT processes. In addition, inhibition of SLC25A22 promoted mitochondrial apoptosis via downregulating BCL-2 and upregulating cleaved PARP, Cytochrome-c, and BAX mediated by MAPK/ERK pathway. Our study identified that SLC25A22 promoted development of GBC activating MAPK/ERK pathway. SLC25A22 has a potential to be used as a target for cancer diagnosis of GBC and related therapies.


Urban American Indian Clinic Smoking Cessation Program.
Cigarette-smoking disparities continue to exist among minority groups of adults, particularly American Indians, who had the highest prevalence of cigarette smoking at 24% in 2017. Implement a nurse practitioner-led smoking cessation pilot program at an urban American Indian health center. The cessation program is based on the "Treating Tobacco Use and Dependence" clinical practice guideline with incorporation of motivational interviewing, and is guided by the Transtheoretical Model of Health Behavior Changes. The program consisted of ten sessions: one in-person visit and nine telephone sessions over the course of eight weeks. Evaluation of project objectives was achieved through the collection of qualitative and quantitative data via weekly phone counseling sessions and a final follow-up phone call. Among program participants (n = 5), three achieved complete cessation, one decreased their smoking behavior, and one experienced no change in smoking behavior. Although the program is effective among participants who completed the program, attrition was a significant issue requiring potential future changes to the program design.


Diabetic neuropathy in the upper limb and the effect of twelve months sorbinil treatment.
Clinical and neurophysiological studies were undertaken, with particular reference to the arms, in 39 patients with diabetic neuropathy. The effects of an aldose reductase inhibitor, sorbinil, on neuropathy in these patients were studied in a 12 month double blind placebo controlled trial. Neurophysiological measurements, particularly of sensory amplitude, were considerably more sensitive than measurements of temperature and vibration sensation and remain of fundamental importance in measuring diabetic neuropathy at an early and potentially reversible stage. There was no significantly beneficial effect of sorbinil on clinical or neurophysiological measurements of nerve function in patients with established diabetic neuropathy. These results indicate that neurophysiological techniques are necessary, in conjunction with clinical measurements, for the assessment of 'early' diabetic neuropathy and that aldose reductase inhibitors are not effective in the treatment of established diabetic neuropathy.


MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease.
Modulation of the subventricular zone (SVZ) neurogenic niche can enhance brain repair in several disorders including Parkinson's disease (PD). Herein, we used biocompatible and traceable polymeric nanoparticles (NPs) containing perfluoro-1,5-crown ether (PFCE) and coated with protamine sulfate to complex microRNA-124 (miR-124), a neuronal fate determinant. The ability of NPs to efficiently deliver miR-124 and prompt SVZ neurogenesis and brain repair in PD was evaluated. In vitro, miR-124 NPs were efficiently internalized by neural stem/progenitors cells and neuroblasts and promoted their neuronal commitment and maturation. The expression of Sox9 and Jagged1, two miR-124 targets and stemness-related genes, were also decreased upon miR-124 NP treatment. In vivo, the intracerebral administration of miR-124 NPs increased the number of migrating neuroblasts that reached the granule cell layer of the olfactory bulb, both in healthy and in a 6-hydroxydopamine (6-OHDA) mouse model for PD. MiR-124 NPs were also able to induce migration of neurons into the lesioned striatum of 6-OHDA-treated mice. Most importantly, miR-124 NPs proved to ameliorate motor symptoms of 6-OHDA mice, monitored by the apomorphine-induced rotation test. Altogether, we provide clear evidences to support the use of miR-124 NPs as a new therapeutic approach to boost endogenous brain repair mechanisms in a setting of neurodegeneration.


Growth hormone: species-specific stimulation of erythropoiesis in vitro.
The effects of purifed bovine and human growth hormone were tested in vitro with murine and human bone marrow by means of granulocyte-monocyte and erythroid progenitor cloning techniques. Nanogram concentrations of the growth hormones potentiated erythropoietin-stimulated erythropoiesis, but not granulopoiesis, in a species-specific manner.


Single Marker Association Analysis for Unrelated Samples.
Methods for single marker association analysis are presented for binary and quantitative traits. For a binary trait, we focus on the analysis of retrospective case-control data using Pearson's chi-squared test, the trend test and a robust test. For a continuous trait, typical methods are based on a linear regression model or the analysis of variance. We illustrate how these tests can be applied using a publicly available R package "Rassoc" and some existing R functions. Guidelines for single-marker analysis are provided.


Effect of a plasma grating on pump-probe experiments near the ionization threshold in gases.
Calculations are performed of the phase shift caused by the spatial modulation in the plasma density due to interference between a strong pump pulse and a weak probe pulse. It is suggested that a recent experiment [Opt. Express 17, 13429 (2009)] observed an effective birefringence from this plasma grating rather than from the higher-order Kerr effect.


Myocardial contrast echocardiography can be used to assess the microvascular response to vascular endothelial growth factor-121.
Therapeutic angiogenesis is a new approach to treating ischemic heart disease, and the optimal method for assessing its efficacy is unclear. We used myocardial contrast echocardiography (MCE) to evaluate the therapeutic response to the angiogenic agent, vascular endothelial growth factor-121 (VEGF121). After placement of an ameroid constrictor (day 0) around the left anterior descending artery (LAD), dogs were given intracoronary VEGF121 protein (108 microg, n=6) or placebo (n=6) on days 7 and 21, and subcutaneous VEGF121 (1 mg) or placebo on days 8 to 20 and 22 to 27. On day 48, MCE was performed during rest and dobutamine stress. Videointensity (y) and pulsing interval (t) were fit to an exponential model (y=A[1-e(-beta(t))]) used to derive indices of red cell velocity (beta) and capillary area (A), and parameters were compared with radiolabeled microsphere flow data. VEGF(121) treatment resulted in higher resting left anterior descending artery/left circumflex flow ratio compared with placebo (P<0.03) and improved collateral flow reserve. Beta was 0.94+/-0.37 in VEGF121 dogs versus 0.38+/-0.31 in controls (P<0.02), with the greatest difference in the endocardium. The parameter A was comparable in both groups, suggesting that microvascular changes did not alter capillary cross-sectional area, and histology indicated a trend toward higher arteriolar density in VEGF121-treated animals. VEGF121 protein improves collateral flow and reserve. MCE can evaluate the transmural location and structural and functional responses of the microvasculature to angiogenic interventions.


Changes in drug susceptibility and toxin genes in Staphylococcus aureus isolated from blood cultures at a university hospital.
We studied changes in toxin-producing genes and drug susceptibility in Staphylococcus aureus isolated from blood cultures at the University of Tokyo Hospital between 1980-1984 (six mecA gene-positive methicillin resistant S. aureus [MRSA] strains and 20 mecA gene-negative methicillin-susceptible S. aureus [MSSA] strains) and 1999 (11 MRSA and 20 MSSA strains). The prevalence of strains with toxin-producing genes increased from 66.7% to 90.9% in MRSA, and from 30.0% to 55.0% in MSSA during the interval. Among toxin-producing gene-positive S. aureus, the dominant strains shifted from those with the enterotoxin (ET) - A gene in 1980-1984 to those with both the toxic shock syndrome toxin-1 and the ET-C genes in 1999. All strains were susceptible to vancomycin and teicoplanin. Mupirocin and arbekacin inhibited all strains at concentrations of less than or equal to 0.5 micro g/ml and 4 micro g/ml, respectively. More than half of the MRSA strains in 1999 were considered to be nonsusceptible to flomoxef. Because almost all MRSA and more than half of MSSA among recently isolated strains possessed the toxin-producing genes, we should pay attention to whether toxin-related diseases caused by MRSA and MSSA are increasing.


Projections of the posterodorsal preoptic nucleus and the lateral part of the posterodorsal medial amygdala in male gerbils, with emphasis on cells activated with ejaculation.
The posterodorsal preoptic nucleus (PdPN) and the lateral part of the posterodorsal medial amygdala (MeApd) express Fos with ejaculation in male gerbils. Ejaculation-activated cells participate in the PdPN and MeApd projections to each other and to the sexually dimorphic preoptic area (SDA), but those projections involve less than 20% of the activated PdPN cells and less than 50% of the activated MeApd cells. To identify other potential targets of ejaculation-activated cells, we traced PdPN and lateral MeApd outputs using biotinylated dextran amine. The principal part of the bed nucleus of the stria terminalis (BSTpr) and the anteroventral periventricular nucleus (AVPv) were labeled from both sites and were injected with Fluoro-Gold to determine whether PdPN and lateral MeApd cells that express Fos with ejaculation would be retrogradely labeled. Fluoro-Gold was also applied to the dorsomedial hypothalamus (DMH) and retrorubral field (RRF) because such injections label PdPN cells in rats. The PdPN-DMH projection is minimal in gerbils, involving few, if any, ejaculation-related cells. Ejaculation-activated PdPN cells project to the AVPv (43%), dorsal BSTpr (30%), and RRF (12%). Those in the lateral MeApd project to the dorsal BSTpr (43%) and AVPv (18%). When these percentages are combined with those for ejaculation-activated cells involved in the PdPN and lateral MeApd projections to each other and to the medial SDA, the totals reach 100%. Thus, every PdPN and MeApd cell activated with ejaculation may participate in one of these projections. Similar projections may contribute to the similar behavioral effects of the PdPN and MeApd.


Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases.
Polyglutamine (poly-Q) diseases are late-onset neurodegenerative disorders arising from the expansion of an unstable CAG repeat in the affected gene, which is translated to a tract of glutamine residues. This kind of mutant proteins may be aggregated and accumulated, and thereby enhance cellular oxidative stress. In one of our previous studies (Free Radic. Res. 2003;37:1307-17), we found that alteration in the leukocyte mtDNA content is very sensitive to the level of oxidative stress in blood. Thus, we proposed that leukocyte mtDNA content may be used as a biomarker to predict the severity of clinical manifestation of poly-Q diseases. We recruited 50 healthy subjects and 114 patients with poly-Q diseases, including spinal cerebellar atrophy 2/3, spinal bulbar muscular atrophy, and Huntington chorea. We found that mtDNA in leukocytes was depleted in patients with poly-Q diseases (P<0.05). Moreover, the results showed that patients with lower mtDNA content more frequently manifested multiple-symptom disorders and had high CAG repeat numbers in the mutant genes. In conclusion, we suggest that leukocyte mtDNA content correlates with the length of GAG repeat and may serve as an index of the severity of poly-Q diseases.


Contrast-enhanced ultrasonography vs B-mode ultrasound for visualization of intima-media thickness and detection of plaques in human carotid arteries.
Carotid intima-media thickness (IMT) and plaque are recognized markers of increased risk for cerebrovascular events. Accurate visualization of the IMT and plaques is dependent upon image quality. Ultrasound contrast agents improve image quality during echocardiography-this study assessed whether contrast-enhanced ultrasound (CEUS) improves carotid IMT visualization and plaque detection in an asymptomatic population. Individuals free from known cardiovascular disease, enrolled in a community study, underwent B-mode and CEUS carotid imaging. Each carotid artery was divided into 10 segments (far and near walls of the proximal, mid and distal segments of the common carotid artery, the carotid bulb, and internal carotid artery). Visualization of the IMT complex and plaque assessments was made during both B-mode and CEUS imaging for all enrolled subjects, a total of 175 individuals (mean age 65±9 years). Visualization of the IMT was significantly improved during CEUS compared with B-mode imaging, in both near and far walls of the carotid arteries (% IMT visualization during B-mode vs CEUS imaging: 61% vs 94% and 66% vs 95% for right and left carotid arteries, respectively, P<.001 for both). Additionally, a greater number of plaques were detected during CEUS imaging compared with B-mode imaging (367 plaques vs 350 plaques, P=.02). Contrast-enhanced ultrasound improves visualization of the intima-media complex, in both near and far walls, of the common and internal carotid arteries and permits greater detection of carotid plaques. Further studies are required to determine whether there is incremental clinical and prognostic benefit related to superior plaque detection by CEUS.


Can the International Index of Erectile Function distinguish between organic and psychogenic erectile function?
To define the ability of the International Index of Erectile Function (IIEF) to differentiate between organic and psychogenic erectile dysfunction (ED). Patients presenting for the evaluation and treatment of ED who had penile duplex Doppler ultrasonography (DUS) completed the IIEF questionnaire. Accepted ranges of the IIEF EF domain were used to grade baseline severity (severe, moderate and mild < or =11, 11-17, 18-25, respectively). Accepted criteria were used to define normality on DUS (peak systolic velocity >30 cm/s and end-diastolic velocity <5 cm/s). Patients with documented Peyronie's disease, hypogonadism and a history of radical prostatectomy were excluded. In all, 112 patients were enrolled, with a mean (sd) age and duration of ED of 56 (16) and 2 (0.6) years, respectively. The vascular risk-factor profile included diabetes in 15%, hypertension in 26% and hyperlipidaemia in 20%. The baseline severity of ED was mild, moderate and severe in 28%, 41% and 32% men, respectively. All patients had normal testosterone levels. Patients also with a normal DUS were diagnosed with psychogenic ED, in 50%, 13% and 17% of men with mild, moderate and severe ED by the IIEF, respectively. No patient with venous leak had mild ED, and 62% of men with venous leak had severe ED. These results indicate that the IIEF is not completely accurate in differentiating between organic and psychogenic ED, and that almost a fifth of men in this study population with severe ED by the IIEF had normal erectile haemodynamics. These data have potential ramifications for evaluating the baseline severity of ED in trials of erectogenic agents.


Prognostic values of the factor Xa-activated clotting time and endogenous thrombin potential in patients suspected of having disseminated intravascular coagulation.
Widespread coagulation activation and intravascular fibrin formation are clinical features of disseminated intravascular coagulation (DIC). The endogenous thrombin potential (ETP) has been shown to be a useful marker for hypo- or hypercoagulability. The factor Xa-activated clotting time (XACT) represents plasma levels of procoagulant phospholipids. We investigated whether the ETP and XACT would be good prognostic markers in patients suspected of having DIC and whether these markers would show a significant correlation with the thrombin-antithrombin complex (TAT), a marker of in vivo coagulation activation. One hundred twenty-nine patients suspected of having DIC were enrolled for the study. The TAT was measured by ELISA. The ETP and XACT were measured by calibrated automated thrombinography. The 28-day mortality was used as a predictor of clinical outcomes. In overt DIC, higher XACT (9.67 vs. 7.33 min) and higher TAT (26.15 vs. 11.56 ng/ml) results were obtained from the nonsurvivors than from the survivors. ETP levels were lower in the overt DIC group than in the no overt DIC group. In receiver operating characteristic analysis, which was conducted to predict the 28-day mortality, the areas under the receiver operating characteristic analysis curve were as follows: 0.71 (95% CI: 0.62-0.78) for the XACT, 0.70 (0.61-0.77) for the TAT, and 0.64 (0.55-0.72) for the ETP. For the diagnosis of overt DIC, the area under the curve of XACT, TAT and ETP were 0.77 (0.69-0.84), 0.64 (0.55-0.72) and 0.73 (0.64-0.80), respectively. The odds ratio of the XACT for the relative risk of 28-day mortality was 9.60 (3.53-26.11), and that of the TAT was 5.18 (2.11-12.72) and that of the ETP 7.66 (1.67-35.17). For the diagnosis of overt DIC, the odds ratio of XACT, TAT and ETP were 37.35 (4.86-286.89), 4.89 (1.93-12.43) and 4.89 (1.98-12.09), respectively. There was a negative correlation between the TAT and ETP (r=-0.223, P=0.012) and a positive correlation between the TAT and XACT (r=0.251, P=0.004). Our results suggest that the XACT and ETP may be useful diagnostic and prognostic markers for the DIC. Among various markers, the XACT serves as a good prediction of the 28-day mortality in patients suspected of having DIC.


Maternal infection in pregnancy and risk of asthma in offspring.
This study estimates the effect of maternal infections during pregnancy on childhood asthma. One-thousand four-hundred and twenty-eight pregnant women were prospectively followed using structured interviews and chart review until their child's 6th year of life. Infections were identified from outpatient and hospital visits. Childhood asthma was defined as physician diagnosis with symptoms at age six. Adjusted odds ratios were calculated from multivariable logistic regression models. Six-hundred and thirty-five women experienced an infection during pregnancy. Among antepartum infections, maternal urinary tract infections were significantly associated with childhood asthma (aOR 1.60, 95 % CI 1.12-2.29). Chorioamnionitis and maternal group beta streptococcus colonization were not significantly associated with an increased risk in childhood asthma. This study found an increased risk of asthma in children of women diagnosed with urinary tract infections during pregnancy, while other maternal infections did not increase the risk.


Crystal structure of FadD32, an enzyme essential for mycolic acid biosynthesis in mycobacteria.
Fatty acid degradation protein D32 (FadD32), an enzyme required for mycolic acid biosynthesis and essential for mycobacterial growth, has recently been identified as a valid and promising target for anti-tuberculosis drug development. Here we report the crystal structures of Mycobacterium smegmatis FadD32 in the apo and ATP-bound states at 2.4 Å and 2.25 Å resolution, respectively. FadD32 consists of two globular domains connected by a flexible linker. ATP binds in a cleft at the interface between the N- and C-terminal domains and its binding induces significant local conformational changes in FadD32. The binding sites of meromycolic acid and phosphopantetheine are identified by structural comparison with other members of the adenylating enzyme superfamily. These results will improve our understanding of the catalytic mechanism of FadD32 and help in the design of inhibitors of this essential enzyme.


Pregnancy scares, pregnancy uncertainty, and abortion attitude change.
Women's attitudes towards abortion are often assessed infrequently in their lives. This measurement may not capture how lifetime events, such as reproductive experiences, potentially influence attitudes towards abortion. Although reproductive attitudes can fluctuate with life's circumstances, there is little research on how abortion attitudes may change when a woman suspects she might be pregnant. Using an intensive longitudinal dataset collected in Michigan, the Relationship Dynamics and Social Life (RDSL) study (2008-2012), we test the relationship between the timing of pregnancy scares and uncertainty and abortion attitudes using hybrid effects models. We find that women become less supportive of abortion while experiencing a pregnancy scare or uncertainty; however, this association exists only during a scare or uncertainty. These findings highlight that abortion attitudes may change when a woman suspects she might be pregnant. However, attitudinal change may not last past this period.


Developmental expression of dysbindin in Muller cells of rat retina.
Dysbindin, the product of the DTNBP1 gene, was identified by yeast two hybrid assay as a binding partner of dystrobrevin, a cytosolic component of the dystrophin protein complex. Although its functional role has not yet been completely elucidated, the finding that dysbindin assembles into the biogenesis of lysosome related organelles complex 1 (BLOC-1) suggests that it participates in intracellular trafficking and biogenesis of organelles and vesicles. Dysbindin is ubiquitous and in brain is expressed primarily in neurons. Variations at the dysbindin gene have been associated with increased risk for schizophrenia. As anomalies in retinal function have been reported in patients suffering from neuropsychiatric disorders, we investigated the expression of dysbindin in the retina. Our results show that differentially regulated dysbindin isoforms are expressed in rat retina during postnatal maturation. Interestingly, we found that dysbindin is mainly localized in Müller cells. The identification of dysbindin in glial cells may open new perspectives for a better understanding of the functional involvement of this protein in visual alterations associated to neuropsychiatric disorders.


Universal correlation between solvent polarity, fluorescence lifetime and macroscopic viscosity of alcohol solutions.
In this report, we show interesting correlation between solvent polarity of alcohol solutions and fluorescence lifetime (τ(av)), estimated from time-resolved fluorescence spectroscopy (TRFS), and macroscopic viscosity (η). Non-functionalized carbon nanoparticles (NCNP) were successfully used as flurophores in these measurements. The solvent polarity, described through polarizability (Δf) of dielectric continuum theory, could universally describe both τ(av)/τ(max) and η/η(max) through the relation, [Formula: see text] with X = τ(av)/τ(max) or η/η(max), (subscript OH represents corresponding values for alcohols) for alcohol solutions of methanol, ethanol and 1-propanol at room temperature. We show that fluorescence lifetime and solvent viscosity are universal functions of solvent polarity for alcohol solutions.


Variations in lipoproteins, hormones and blood glucose during the early acute phase of myocardial infarction.
This study reports on 22 patients (18 men, 4 women), 45-83-year-old admitted to hospital less than 24 h after the first clinical signs of myocardial infarction. Lipids, lipoproteins, serum insulin and growth hormone, urinary cortisol and vanillylmandelic acid and blood glucose were analysed on the day of admission (day 1) and on days 2, 4 and 8 of the acute phase. Results for lipoproteins generally confirm those of earlier studies: lowered total cholesterol (day 1-8), LDL-cholesterol (day 1-2), HDL-cholesterol (day 2-8), LDL apo B (day 1-2) and apo A-1 (day 1-8). There was no significant correlation between stress hormone and plasma lipoprotein alterations. Blood glucose decreased progressively (P less than 0.05) between day 1 and day 8. Glucose value at day 1 correlated significantly with nonesterified fatty acids, total cholesterol and LDL constituents, but not with HDL-cholesterol and apo A-1. Metabolic disturbances modifying blood glucose thus might be involved in LDL changes, whereas other processes govern HDL changes.


Determining the temporal development of dentin-composite bond strength during curing.
As composite restorations cure a competition develops between bond formation and shrinkage stress at the composite-dentin interface. Thus, understanding the temporal development of tooth-composite bond strength should enable better assessment of tooth-composite debonding. In this study, bond strengths of composite-dentin specimens obtained from tensile test at different curing times were used to determine the bond formation rate. By varying the composite thickness and output from the curing light, their effects on the rate of bond formation for two different materials (a conventional and a bulk-fill composite) were also investigated. The proportions of cohesive and adhesive failure were determined by analysis of electron micrographs of the fractured surfaces. The development of dentin-composite bond strength (S) with time (t) can be described by the equation: S=Smax(1-exp(-αt)), where Smax is the final bond strength (∼12MPa for both composites) and α the rate of bond formation. Using bulk-fill and thinner specimens gave faster bond formation. In fact, the higher the irradiance at the interface, the higher the rate of bond formation. However, α had a maximum value of ∼0.6s(-1) and the rule of reciprocity did not hold. A minimum dose of ∼2J/cm(2) was required to achieve adequate bond strength. The predominant failure mode changed from cohesive in the composite and adhesive to interfacial at the adhesive-dentin interface, indicating the latter to be the weakest link in the cured dentin-composite assemblies considered. When combined with the temporal development of shrinkage stress, the current results will help determine the likelihood of tooth-composite debonding.


Evolution of carotene desaturation: the complication of a simple pathway.
In a series of desaturation reactions, the trienoic structures of phytoene and diapophytoene are extended to a maximum of 15 or 11 conjugated double bonds, respectively. After the cloning of several genes from bacteria and eukaryotes, the desaturation reactions were first analyzed in a heterologous host by functional genetic complementation. In addition, different desaturases were heterologously expressed and the reactions studied in vitro. This revealed that in archaea, non-photosynthetic prokaryotes and fungi the desaturases differ significantly from convergently evolved desaturases in cyanobacteria, Chlorobaculum (old name Chlorobium) species and eukaryotic photosynthetic organisms including plants. Detailed analysis of the desaturation reactions including the determination of the substrates converted by the enzymes, the intermediates and the products formed in the reactions revealed the bacterial all-trans desaturation pathway catalyzed by a single enzyme and the cyanobacterial/plant type poly-cis desaturation pathway which involves two closely related desaturases. This indicates that in the course of evolution of carotenogenesis from bacteria via cyanobacteria to plants, the simple situation of one enzyme for the entire reaction sequence from phytoene to all-trans lycopene changed to a more complex process. Three individual enzymes, newly acquired phytoene and zeta-carotene desaturases, as well as a carotene isomerase which is phylogenetically related to CrtI are involved. Only the CrtI-type enzymes seem to have the property to catalyze cis to trans conversion of carotenes.


Brain mineralocorticoid receptor diversity: functional implications.
Mineralocorticoid receptors (MRs) in neurons of the anterior hypothalamus and the periventricular brain regions mediate aldosterone-selective actions on sodium homeostasis, salt appetite and cardiovascular regulation. Corticosterone is not effective in these neurons, possibly because it is enzymatically inactivated. However, MRs in limbic brain regions, notably in the hippocampal neurons, do already respond to very low concentrations of both corticosterone and aldosterone. The MR-mediated effects stabilize neuronal transmission and appear critical for neuronal integrity of a sub-region of the hippocampus: the dentate gyrus. Higher concentrations of corticosterone induced by stress and the circadian rise progressively activate the lower affinity glucocorticoid receptors (GRs), which in coordination with MR-mediated actions then facilitate adaptive processes required for recovery of homeostasis. It is postulated that this balanced MR- and GR-mediated action of corticosterone is of critical importance for regulation of the stress response and behavioural adaptation.


Eco-physiological studies on desert plants : III. Respiration of negatively photoblastic Zygophyllum coccineum L. seeds during germination.
The O2 uptake and RQ of germinating negatively photoblastic Zygophyllum coccineum seeds were studied during the first fourty hours after soaking in water under dark or light conditions. Five phases could be distinguished in the course of O2 uptake in water in dark. The respiration course in light did not differ from that in dark till the 12th hour after soaking, then it deviated showing a low level, The RQ values in dark and light are nearly identical; both had sharp decline between the 8th and the 16th hour after soaking. Light, by blocking germination, affected the O2 uptake.Moisture stress simulated by mannitol solutions caused a decrease in the O2 uptake of seeds and seedlings. Na2SO4 caused a reduction and a lag in the time of maximum O2 uptake. NaCl showed a particular effect on respiration of germinating seeds causing earlier rise and decrease in O2 uptake than in water. NaCl was effective in rising the O2 uptake of seedlings specially those supplied with glucose. Its effect was not pronounced on starved seedlings. O2 uptake of seedlings germinated in NaCl was considerably high when compared with that of seeds germinating in the same medium 40 hours after soaking.The decreasing effect of moisture stress caused by mannitol on O2 uptake was reversed by diluting the medium or replacing it with water. Values of O2 uptake on number of seedlings basis are different from those calculated on fresh weight basis due to the difference in water content of seedlings germinated under various conditions.


Physical examination tests and imaging studies based on arthroscopic assessment of the long head of biceps tendon are invalid.
The aim of this study was to evaluate whether glenohumeral arthroscopy is an appropriate gold standard for the diagnosis of long head of biceps (LHB) tendon pathology. The objectives were to evaluate whether the length of tendon that can be seen at arthroscopy allows visualisation of areas of predilection of pathology and also to determine the rates of missed diagnoses at arthroscopy when compared to an open approach. A systematic review of cadaveric and clinical studies was performed. The search strategy was applied to MEDLINE, PubMed and Google Scholar databases. All relevant articles were included. Critical appraisal of clinical studies was performed using a validated quality assessment scale. Five articles were identified for inclusion in the review. This included both clinical and cadaveric studies. The overall population comprised 18 cadaveric specimens and 575 patients. Out of the five included studies, three reported the length of LHB tendon visualised during arthroscopy and four reported the rate of missed LHB diagnosis. Cadaveric studies showed that the use of a hook probe allowed arthroscopic visualisation of between 34 and 48 % of the overall length of the LHB. In the clinical series, the rate of missed diagnoses at arthroscopy when compared to open exploration ranged between 33 and 49 %. Arthroscopy allows visualisation of only a small part of the extra-articular LHB tendon. This leads to a high rate of missed pathology in the distal part of the tendon. Published figures for sensitivities and specificities of common physical examination and imaging tests for LHB pathology that are based on arthroscopy as the gold standard are therefore invalid. In clinical practice, it is important to note that a "negative" arthroscopic assessment does not exclude a lesion of the LHB tendon as this technique does not allow visualisation of common sites of distal pathology. IV.


Characterization of whole cell chloride conductances in a mouse inner medullary collecting duct cell line mIMCD-3.
The chloride conductance of inner medullary collecting duct cells (mIMCD-3 cell line) has been investigated using the whole cell configuration of the patch clamp technique. Seventy-seven percent of cells were chloride selective when measured with a NaCl-rich bathing solution and a TEACl-rich pipette solution. Seventy-five percent of chloride-selective cells (90/144) had whole cell currents which exhibited an outwardly-rectifying (OR) current-voltage (I/V) relationship, while the remaining cells exhibited a linear (L) I/V relationship. The properties of the OR and L chloride currents were distinct. OR currents (mean current densities at +/- 60 mV of 66 +/- 5 pA/pF and 44 +/- 3 pA/pF), were time- and voltage-independent with an anion selectivity (from calculated permeability ratios) of SCN- (2.3), NO3- (1.8), ClO4- (1.7), Br- (1.7), I- (1.6), Cl- (1.0), HCO3- (0.5), gluconate- (0.2). Bath additions of NPPB, flufenamate, glibenclamide (all 100 microM) and DIDS (500 microM) produced varying degrees of block of OR currents with NPPB being the most potent (IC50 of approximately 50 microM) while DIDS was the least effective. Linear chloride currents had similar current densities to the OR chloride currents and were also time- and voltage-independent. The anion selectivity sequence was SCN- (2.5), NO3- (1.9), Br- (1.4), I- (1.1), Cl- (1.0), ClO4- (0.5), HCO3- (0.5), gluconate- (0.3). In contrast to the OR conductance, glibenclamide was the most potent and DIDS the least potent blocker of L currents. An IC50 of > 100 microM was observed for NPPB block. Neither OR of L chloride currents were affected by acutely or chronically increased intracellular cAMP and were not affected when intracellular Ca2+ levels were increased or decreased. The molecular identity and physiological role of OR and linear currents in mIMCD-3 cells are discussed.


Hippocampal spindles and barques are normal intracranial electroencephalographic entities.
To assess whether hippocampal spindles and barques are markers of epileptogenicity. Focal epilepsy patients that underwent stereo-electroencephalography implantation with at least one electrode in their hippocampus were selected (n = 75). The occurrence of spindles and barques in the hippocampus was evaluated in each patient. We created pairs of pathologic and pathology-free groups according to two sets of criteria: 1. Non-invasive diagnostic criteria (patients grouped according to focal epilepsy classification). 2. Intracranial neurophysiological criteria (patient's hippocampi grouped according to their seizure onset involvement). Hippocampal spindles and barques appear equally often in both pathologic and pathology-free groups, both for non-invasive (Pspindles = 0.73; Pbarques = 0.46) and intracranial criteria (Pspindles = 0.08; Pbarques = 0.26). In Engel Class I patients, spindles occurred with similar incidence both within the non-invasive (P = 0.67) and the intracranial criteria group (P = 0.20). Barques were significantly more frequent in extra-temporal lobe epilepsy defined by either non-invasive (P = 0.01) or intracranial (P = 0.01) criteria. Both spindles and barques are normal entities of the hippocampal intracranial electroencephalogram. The presence of barques may also signify lack of epileptogenic properties in the hippocampus. Understanding that hippocampal spindles and barques do not reflect epileptogenicity is critical for correct interpretation of epilepsy surgery evaluations and appropriate surgical treatment selection.


[Surgical reconstructive treatment of blood vessels in the popliteal region].
Severe occlusive disease frequently includes the popliteal artery and origin of the trifurcation vessels with reconstruction of one or more of the crural arteries. We made femorocrural bypass 23 times. Our indications for operation continue to be relief of pain or salvage of extremity. Of the 23 grafts during of one year period block recurred in 8 patients. Five times we made amputation and good results we had in 15 patients. In one patient we used Gore-tex prosthesis with succses in 4 month period.


Infrared spectrometry and Raman microprobe in the analysis of urinary calculi.
Infrared spectrophotometry and Raman spectroscopy, thanks to the laser molecular microsond (MOLE), are two analytical techniques particularly well suited to a precise analysis of the composition and structure of urinary calculi. They both showed noteworthy efficiency in their ability to recognize the various crystalline or amorphous mineral and organic species. The MOLE permits analysis of crystals 1 mu in size, demonstrating its usefulness in the study of calculi nuclei as well as in the study of urinary crystals. These analyses are a very important source of information about conditions of crystalline nucleation and growth as well as about ions and molecules which can take place in the formation and the evolution of the diverse crystalline phases. On the clinical level, these data can contribute to a better comprehension of the formation of every stone.


Comparison of insect, fungal, and mechanically induced defoliation of larch: effects on plant productivity and subsequent host susceptibility.
Larch sawfly, Pristiphora erichsonii Hartig, and larch needlecast fungus, Mycosphaerella laricinia (R. Hartig) Neg., are early season defoliators restricted only to Larix host trees. Larch defoliation (100%) by either the fungus or insect, but not mechanical removal, induced systemic responses that reduced sawfly consumption and digestion rates one year later. In a feeding behavior assay, larvae quickly abandoned seedlings previously defoliated by M. laricinia. Adult female oviposition choice and egg deposition were unaffected. Seedling growth was not affected during the year of defoliation by M. laricinia, but was significantly reduced one year later. Defoliation by M. laricinia reduced stem volume, radial growth, root biomass and new shoot production. The latter tissue is the only oviposition resource for larch sawfly, and, in contrast, is not influenced by sawfly feeding. We hypothesize that M. laricinia infection may limit larch sawfly populations where both species coexist. However, this reduction is at a substantial net cost to larch productivity.


Nutrient conditions mediate mycorrhizal effects on biomass production and cell wall chemistry in poplar.
Large-scale biofuel production from lignocellulosic feedstock is limited by the financial and environmental costs associated with growing and processing lignocellulosic material and the resilience of these plants to environmental stress. Symbiotic associations with arbuscular (AM) and ectomycorrhizal (EM) fungi represent a potential strategy for expanding feedstock production while reducing nutrient inputs. Comparing AM and EM effects on wood production and chemical composition is a necessary step in developing biofuel feedstocks. Here, we assessed the productivity, biomass allocation and secondary cell wall (SCW) composition of greenhouse-grown Populus tremuloidesMichx. inoculated with either AM or EM fungi. Given the long-term goal of reducing nutrient inputs for biofuel production, we further tested the effects of nutrient availability and nitrogen:phosphorus stoichiometry on mycorrhizal responses. Associations with both AM and EM fungi increased plant biomass by 14-74% depending on the nutrient conditions but had minimal effects on SCW composition. Mycorrhizal plants, especially those inoculated with EM fungi, also allocated a greater portion of their biomass to roots, which could be beneficial in the field where plants are likely to experience both water and nutrient stress. Leaf nutrient content was weakly but positively correlated with wood production in mycorrhizal plants. Surprisingly, phosphorus played a larger role in EM plants compared with AM plants. Relative nitrogen and phosphorus availability were correlated with shifts in SCW composition. For AM associations, the benefit of increased wood biomass may be partially offset by increased lignin content, a trait that affects downstream processing of lignocellulosic tissue for biofuels. By comparing AM and EM effects on the productivity and chemical composition of lignocellulosic tissue, this work links broad functional diversity in mycorrhizal associations to key biofuel traits and highlights the importance of considering both biotic and abiotic factors when developing strategies for sustainable biofuel production.


Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate.
The two-component phosphorylation network is of critical importance for bacterial growth and physiology. Here, we address plasticity and interconnection of distinct signal transduction pathways within this network. In Caulobacter crescentus antagonistic activities of the PleC phosphatase and DivJ kinase localized at opposite cell poles control the phosphorylation state and subcellular localization of the cell fate determinator protein DivK. We show that DivK functions as an allosteric regulator that switches PleC from a phosphatase into an autokinase state and thereby mediates a cyclic di-GMP-dependent morphogenetic program. Through allosteric activation of the DivJ autokinase, DivK also stimulates its own phosphorylation and polar localization. These data suggest that DivK is the central effector of an integrated circuit that operates via spatially organized feedback loops to control asymmetry and cell fate determination in C. crescentus. Thus, single domain response regulators can facilitate crosstalk, feedback control, and long-range communication among members of the two-component network.


ILAE Classification of Seizures and Epilepsies: An Update for the Pediatrician.
The International League Against Epilepsy (ILAE) recently published an updated classification of seizures and epilepsy. This updated classification aims to have a better organized classification and ensure better understanding of terms, in addition to including new seizure types. As both seizures and epilepsy are important childhood conditions, we herein list some of the important aspects of the updated classification for the benefit of the general pediatricians. The full classifications are available at the ILAE website.


Pharmacokinetics of lidocaine and bupivacaine in retrobulbar and facial block.
Analgesia can be obtained during ophthalmic surgery by regional anesthesia using local anesthetic agents. As in other indications, neurological complications may occur, especially because the site of injection is close to the central nervous system. In order to evaluate the risk of retrobulbar and facial block obtained after 40 mg lidocaine and 20 mg bupivacaine injection, pharmacokinetics of both drugs was evaluated in plasma obtained from 11 patients. In addition, 3 cerebrospinal fluid samples were analyzed. Maximal plasma concentration was 0.73 +/- 0.33 micrograms.ml-1 for lidocaine and 0.19 +/- 0.06 micrograms.ml-1 for bupivacaine, obtained 24.7 +/- 23.0 min and 12.0 +/- 3.7 min after the end of injection, respectively. CSF/plasma ratio was in the range 0.05-0.26 for lidocaine and 0.56-1.33 for bupivacaine. In all patients, regional anesthesia was sufficient to perform surgery without any other analgesic drug. No sign of cardiovascular or respiratory toxicity was observed during the study.


Evaluation of Risk of Major Adverse Cardiovascular Events with Biologic Therapy in Patients with Psoriasis (Errata).
Erratum for "Evaluation of Risk of Major Adverse Cardiovascular Events with Biologic Therapy in Patients with Psoriasis." Retrieved from http://jddonline.com/articles/dermatology/S1545961617P1002X/J Drugs Dermatol 2017;16(10):1002-1013. J Drugs Dermatol 2020;19:e28-e32.


Implementing a pilot work injury management program in Hong Kong.
This paper reports the results of implementing a pilot case management system for work injuries in Hong Kong. The case management approach was characterized by use of a case manager who worked closely with each of the reported injury cases. The case manager undertook the roles of assessor, referral agent, counselor, work-site liaison, and return-to-work (RTW) expert. A quasi-experimental study design was used. The study compared the RTW and workers' compensation outcomes in injured workers in a cleaning company in a case management group (n = 296) and a conventional rehabilitation group (n = 137). Outcomes of the intervention were followed up at 6 months. The results indicated that the RTW rate was 97.0% and 94.2% for the case management and conventional rehabilitation groups respectively, with no significant differences between them. Participants in the case management group had significantly fewer days of sick leave (mean = 27.5 and 41.6 days, respectively) and lower compensation costs (mean = HK$7,212.2 and $20,617.3, respectively) than those in the comparison group. Age of the participants was found to influence the outcomes with those who were between 41 and 50 years old and received case management intervention had shorter sick leave and lower cost of compensation than their conventional rehabilitation counterpart. The majority of the participants who had returned to work in both the case management (95.8%) and the conventional rehabilitation (96.2%) groups were found to maintain their work status 6 months after the intervention. The findings suggested that applying the case management approach to the Hong Kong workers' compensation system was more effective overall. Nevertheless, the inherent problems associated with implementing such an approach within the existing system, which focuses on compensation and medical interventions, remained unresolved.


Stressing the role of a short linear motif in ataxin-2 condensation.
Ataxin-2, an RNA-binding protein that is conserved across eukaryotes, is involved in stress granule assembly and age-associated neurodegenerative diseases. In this issue of Molecular Cell, Boeynaems et al.1 identify a short linear motif in ataxin-2 as a condensation switch, providing molecular insights into its essential role in cellular stress response.


Intracerebroventricular D-galactose administration impairs memory and alters activity and expression of acetylcholinesterase in the rat.
Tissue accumulation of galactose is a hallmark in classical galactosemia. Cognitive deficit is a symptom of this disease which is poorly understood. The aim of this study was to investigate the effects of intracerebroventricular administration of galactose on memory (inhibitory avoidance and novel object recognition tasks) of adult rats. We also investigated the effects of galactose on acetylcholinesterase (AChE) activity, immunocontent and gene expression in hippocampus and cerebral cortex. Wistar rats received a single injection of galactose (4mM) or saline (control). For behavioral parameters, galactose was injected 1h or 24h previously to the testing. For biochemical assessment, animals were decapitated 1h, 3h or 24h after galactose or saline injection; hippocampus and cerebral cortex were dissected. Results showed that galactose impairs the memory formation process in aversive memory (inhibitory avoidance task) and recognition memory (novel object recognition task) in rats. The activity of AChE was increased, whereas the gene expression of this enzyme was decreased in hippocampus, but not in cerebral cortex. These findings suggest that these changes in AChE may, at least in part, to lead to memory impairment caused by galactose. Taken together, our results can help understand the etiopathology of classical galactosemia.


Strongly adhesive zwitterionic composite hydrogel paints for surgical sutures and blood-contacting devices.
Hydrogels show eminent advantages in biomedical and pharmaceutical fields. However, their application as coating materials for biomedical devices is limited by several key challenges, such as lack of universality, weak mechanical strength, and low adhesion to the substrate. Here we report versatile and tough adhesion composite hydrogel paints (CHPs), which consist of zwitterionic copolymers and microgels, both with reactive groups. The CHPs exhibit tunable rheology and thickness, hydrophilicity, biofouling resistance, durability, and convenient fabrication on metal, polymer, and inorganic surfaces with arbitrary shapes. As a proof-of-concept, the CHP-surgical sutures demonstrate exceptional lubrication, drug delivery, anti-infection, and anti-fibrous capsule properties. Moreover, the CHP-PVC tubing effectively prevents thrombus formation in vitro and ex vivo rabbit blood circulation without anticoagulants. This work provides valuable insights for enhancing and developing integrated hydrogel technologies for biomedical devices. STATEMENT OF SIGNIFICANCE: The combination of hydrogel and biomedical devices can enable numerous existing applications in medicine. In this study, inspired by the principle of microgel reinforcement in industrial paints, we propose a simple and versatile zwitterionic composite hydrogel paints (CHPs) strategy, which can be easily applied to diverse substrates with arbitrary shapes by covalent grafting between complementary groups by brush, dip, or spray. The CHPs integrated universality, tough adhesion, mechanical durability, and anti-biofouling properties because of their unique chemical composition and coating structure design. This strategy provides a simple and versatile route for surface modification of biomedical devices.


Suprarenal occurrence of an adenomatoid tumor.
Adenomatoid tumors are rare, benign mesotheliomas that usually are associated with genito-urinary tract. The suprarenal occurrence of this tumor is uncommon. We present such a case and review the origin of the adenomatoid tumor.


Two stages of programming eye gaze shifts in 3-D space.
Accurate saccadic and vergence eye movements towards selected visual targets are fundamental to perceive the 3-D environment. Despite this importance, shifts in eye gaze are not always perfect given that they are frequently followed by small corrective eye movements. The oculomotor system receives distinct information from various visual cues that may cause incongruity in the planning of a gaze shift. To test this idea, we analyzed eye movements in humans performing a saccade task in a 3-D setting. We show that saccades and vergence movements towards peripheral targets are guided by monocular (perceptual) cues. Approximately 200ms after the start of fixation at the perceived target, a fixational saccade corrected the eye positions to the physical target location. Our findings suggest that shifts in eye gaze occur in two phases; a large eye movement toward the perceived target location followed by a corrective saccade that directs the eyes to the physical target location.


Metabolic studies of a family with massive formiminoglutamic aciduria.
We have described two siblings who excrete massive amounts (up to 3.89 mmol/24 hr) of N-formiminoglutamic acid (FIGLU) in their urine. This unusual compound was isolated from urine, purified, and firmly identified as FIGLU by combined gas chromatography-mass spectrometry. The patients presumably have a deficiency in activity of the hepatic enzyme, glutamate formiminotransferase, which carries out the fourth sequential step in the main pathway of histidine degradation. Unlike children reported previously with this disorder, our patients had normal serum folate levels, had no hematologic abnormalities, and were not mentally retarded. Very small amounts of FIGLU were present in the plasma of one of the patients, but FIGLU was not detectable in the cerebrospinal fluid of either patient. Administration of pharmacologic doses of folic or folinic acid produced a decrease in excretion of FIGLU in urine. Histidine loading caused a small and comparable urinary excretion of FIGLU in the children's parents and in control adult subjects.


Investigation of low-molecular weight organic acids and their spatiotemporal variation characteristics in Hongfeng Lake, China.
The identities and concentrations of low-molecular-weight organic acids (LMWOAs) were determined by ion chromatography throughout a 20-m water column in Hongfeng Lake, China. The spatiotemporal variations of LMWOAs and their contributions to dissolved organic matter (DOM) in a research period of 24 hr were also investigated. The results demonstrated that five LMWOAs (lactic, acetic, pyruvic, sorbic, oxalic acid) were detected, and their total concentration and proportion in DOC were 6.55 micromol/L and 7.47%. Their average levels were 2.50, 0.65, 2.35, 0.96 and 0.09 micromol/L, respectively. LMWOAs were higher during daytime (10:00-18:00 on Jun 13, 2008) than nighttime (21:00-6:00 the next morning), in particular 4.99 micromol/L high in the epilimnion (< or = 1 m water depth), reflecting the fact that direct import from terrigenous sources and photochemical production from humic materials were dominant during LMWOAs' origin and accumulation. The same factors caused LMWOAs to be 0.63 micromol/L in the epilimnion higher than in the hypolimnion. The rapid decrease of total organic acid (TOA) up until 18:00 mainly resulted from bio-uptake and mineralization in the hypolimnion (>1 m water depth). Pyruvic acid increased with time in the epilimnion and decreased in the hypolimnion, largely related to the two contrary processes of continuous degradation and synthesis of macromolecular organic matter during life materials' cycle mediated by organisms. Simultaneously, plankton behavior and thermal stratification played a pivotal role in LMWOAs' behavior in the water column, causing decreasing and increasing profiles. The distribution of LMWOAs represents an interesting resource for biogeochemical research of DOM in aquatic ecosystems.


Health literacy and quality of life in hospitalized heart failure patients: a cross-sectional study.
Heart Failure (HF) treatment may be improved by good knowledge of the disease (Health Literacy) that, despite the well-established role on improving self-care, preventing complications and avoiding worse outcomes, has little evidence on affecting QoL of HF patients. Therefore, the objective of the present study was to evaluate the impact of Health Literacy on QoL in hospitalized HF patients. A cross-sectional exploratory study was conducted with HF patients hospitalized at a public cardiological hospital. Health Literacy was assessed using the "Questionnaire about Heart Failure Patients' Knowledge of Disease" and QoL using the "Minnesota Living with Heart Failure Questionnaire" (MLHFQ). The association between Health Literacy and QoL was assessed by linear regression (P<0.05). 50 patients were included in the study; the mean Health Literacy score was 34.2 ± 15.1 (the majority presenting acceptable or better knowledge). The mean MLHFQ score was 73.5 ± 19.8. The one-year hospital readmission rate (β=+3.8; P=0.009) and the patients' Health Literacy score (β=-0.4; P=0.024) or good knowledge category (β=-20.2; P=0.016) were independently associated with QoL. While the readmission rate was inversely associated with QoL, the better the HF knowledge the better QoL in hospitalized HF patients.


The neural correlates of emotional memory in posttraumatic stress disorder.
Posttraumatic stress disorder (PTSD) is marked by intrusive, chronic, and distressing memories of highly emotional events. Previous research has highlighted the role of the amygdala and its interactions with the hippocampus in mediating the effect of enhanced memory for emotional information in healthy individuals. As the functional integrity of these regions may be compromised in PTSD, the current study examined the neural correlates of emotional memory in PTSD. We used functional magnetic resonance imaging and an event-related subsequent memory recognition paradigm to study amygdala and hippocampus activation in 18 individuals with PTSD and 18 trauma-exposed non-PTSD control participants. Memory enhancement for negative, relative to neutral, pictures was found across all subjects, without significant differences between groups. Relative to the trauma-exposed non-PTSD group, the PTSD group showed exaggerated amygdala activation during the encoding of negative versus neutral pictures. This effect was even more pronounced when the analysis included data from only pictures that were subsequently remembered 1 week later. In the PTSD group, degree of amygdala activation during the encoding of negative versus neutral pictures was positively correlated with hippocampal activation and current PTSD symptom severity. The PTSD group also showed exaggerated hippocampal activation in response to negative pictures that were remembered versus forgotten. Finally, hippocampal activation associated with the successful encoding of negative relative to neutral pictures was significantly greater in the PTSD group. Exaggerated amygdala activation during the encoding of emotionally negative stimuli in PTSD is related to symptom severity and to hippocampal activation.


How item banks and their application can influence measurement practice in rehabilitation medicine: a PROMIS fatigue item bank example.
To illustrate how measurement practices can be advanced by using as an example the fatigue item bank (FIB) and its applications (short forms and computerized adaptive testing [CAT]) that were developed through the National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS) Cooperative Group. Psychometric analysis of data collected by an Internet survey company using item response theory-related techniques. A U.S. general population representative sample collected through the Internet. Respondents used for dimensionality evaluation of the PROMIS FIB (N=603) and item calibrations (N=14,931). Not applicable. Fatigue items (112) developed by the PROMIS fatigue domain working group, 13-item Functional Assessment of Chronic Illness Therapy-Fatigue, and 4-item Medical Outcomes Study 36-Item Short Form Health Survey Vitality scale. The PROMIS FIB version 1, which consists of 95 items, showed acceptable psychometric properties. CAT showed consistently better precision than short forms. However, all 3 short forms showed good precision for most participants in that more than 95% of the sample could be measured precisely with reliability greater than 0.9. Measurement practice can be advanced by using a psychometrically sound measurement tool and its applications. This example shows that CAT and short forms derived from the PROMIS FIB can reliably estimate fatigue reported by the U.S. general population. Evaluation in clinical populations is warranted before the item bank can be used for clinical trials.


Coagulation-membrane filtration of Chlorella vulgaris.
Filtration-based separation of Chlorella vulgaris, a species with excellent potential for CO(2) capture and lipid production, was investigated using a surface-modified hydrophilic polytetrafluoroethylene (PTFE) membrane. Coagulation using polyaluminum chloride (PACl) attained maximum turbidity removal at 200 mg L(-1) as Al(2)O(3). The membrane filtration flux at 1 bar increased as the PACl dose increased, regardless of overdosing in the coagulation stage. The filtered cake at the end of filtration tests peaked in solid content at 10 mg L(-1) as Al(2)O(3), reaching 34% w/w, roughly two times that of the original suspension. Differential scanning calorimetry (DSC) tests demonstrate that the cake with minimum water-solid binding strength produced the driest filter cake. Coagulation using 10 mg L(-1) PACl as Al(2)O(3), followed by PTFE membrane filtration at 1 bar, is an effective process for harvesting C. vulgaris from algal froth.


Simulation-based training programme and preparedness testing for COVID-19 using system integration methodology.
COVID-19 pandemic is presenting serious challenges to the world's healthcare systems. The high communicability of the COVID-19 necessitates robust medical preparedness and vigilance. To report on the simulation-based training and test preparedness activities to prepare healthcare workers (HCWs) for effective and safe handling of patients with COVID-19. Two activities were conducted: simulation-based training to all HCWs and a full-scale unannounced simulation-based disaster exercise at King Fahad Medical City (KFMC). The online module was designed to enhance the knowledge on COVID-19. This module was available to all KFMC staff. The five hands-on practical part of the course was available to frontliner HCWs. The unannounced undercover simulated patients' full-scale COVID-19 simulation-based disaster exercise took place in the emergency department over 3 hours. Six scenarios were executed to test the existing plan in providing care of suspected COVID-19 cases. 2620 HCWs took the online module, 17 courses were conducted and 337 frontliner HCWs were trained. 94% of learners were satisfied and recommended the activity to others. The overall compliance rate of the full-scale COVID-19 disaster drill with infection control guidelines was 90%. Post-drill debriefing sessions recommended reinforcing PPE training, ensuring availability of different sizes of PPEs and developing an algorithm to transfer patients to designated quarantine areas. Simulation-based training and preparedness testing activities are vital in identifying gaps to apply corrective actions immediately. In the presence of a highly hazardous contagious disease like COVID-19, such exercises are a necessity to any healthcare institution.


Lysophosphatidylcholine upregulates LOX-1, chemokine receptors, and activation-related transcription factors in human T-cell line Jurkat.
In arteriosclerosis, activated T cells infiltrating the atherosclerotic lesions are directly involved in the pathogenesis of these vascular disorders. Infiltration and accumulation of T cells into the vascular wall occur at the earliest stage of atherosclerosis. The atherosclerotic lesion also sees the accumulation of modified lipids such as lysophosphatidylcholine (lysoPC), the main phospholipid component of oxidized low-density lipoprotein. However, it remains less clear how lysoPC affects CD4 T cells. Therefore, we assessed the effect of lysoPC on various mRNA expressions in human T cells using real-time quantitative Reverse Transcription-PCR. Exposure of Jurkat cells (a human CD4 T-cell line) to lysoPC resulted in upregulation of CXCR4 and CCR5 chemokine receptors, receptor for oxidized low-density lipoprotein (LOX-1), the transcription factors, nuclear factor-kappa beta (NF-kB) and Yin Yang 1, and target molecules of NF-kB, A1/Bfl1/BCL2A1 and c-IAP1/BIRC2, in a dose-dependent manner. These data indicate that lysoPC is a positive regulator of the inflammatory response in human CD4 T cells. Further, it suggested that lysoPC and CD4 T cells accumulating in atherosclerotic lesions contribute to the development of arteriosclerosis.


Transitional nephrology.
During growth from fetal life to early childhood, renal function and parameters used to assess renal function undergo developmental changes. This article provides a brief review of these maturational changes and how they affect the evaluation and management of young patients with diseases affecting the genitourinary system. Included is a discussion of renal blood flow, glomerular filtration, sodium and water balance, clinical assessment of renal function, and age-related effects of nephrotoxins.


Caspase-10 affects the pathogenesis of primary biliary cholangitis by regulating inflammatory cell death.
Primary biliary cholangitis (PBC) is an autoimmune disease that involves chronic inflammation and injury to biliary epithelial cells. To identify critical genetic factor(s) in PBC patients, we performed whole-exome sequencing of five female siblings, including one unaffected and four affected sisters, in a multi-PBC family, and identified 61 rare heterozygote variants that segregated only within the affected sisters. Among them, we were particularly interested in caspase-10, for although several caspases are involved in cell death, inflammation and autoimmunity, caspase-10 is little known from this perspective. We generated caspase-10 knockout macrophages, and then investigated the obtained phenotypes in comparison to those of its structurally similar protein, caspase-8. Unlike caspase-8, caspase-10 does not play a role during differentiation into macrophages, but after differentiation, it regulates the process of inflammatory cell deaths such as necroptosis and pyroptosis more strongly. Interestingly, caspase-10 displays better protease activity than caspase-8 in the process of RIPK1 cleavage, and an enhanced ability to form a complex with RIPK1 and FADD in human macrophages. Higher inflammatory cell death affected the fibrotic response of hepatic stellate cells; this effect could be recovered by treatment with UDCA and OCA, which are currently approved for PBC patients. Our findings strongly indicate that the defective roles of caspase-10 in macrophages contribute to the pathogenesis of PBC, thereby suggesting a new therapeutic strategy for PBC treatment.


Potential Community and Campus Covid-19 Outcomes Under University and College Reopening Scenarios.
Significant uncertainty exists in many countries about the safety of, and best strategies for, reopening college and university campuses until the Covid-19 pandemic is better controlled. Little also is known about the effects on-campus students may have on local higher-risk communities. We aimed to estimate potential community and campus Covid-19 exposures, infections, and mortality due to various university reopening and precaution plans under current ranges of assumptions and uncertainties. We developed and calibrated campus-only, community-only, and campus-x-community epidemic differential equation and agent-based models. Input parameters for campus and surrounding communities were estimated via published and grey literature, scenario development, expert opinion, accuracy optimization algorithms, and Monte Carlo simulation; models were cross-validated against each other using February-June 2020 data from heterogeneous U.S. counties and states. Campus opening plans (spanning various fully open, hybrid, and fully virtual approaches) were identified from websites and publications. All scenarios were simulated assuming 16-week semesters and estimated ranges for Covid-19 prevalence among community residents and arriving students, precaution compliance, contact frequency, virus attack rates, and tracing and isolation effectiveness. Additional student and community exposures, infections, and mortality were estimated under each scenario, with 10% trimmed medians, standard deviations, and probability intervals computed to omit extreme outlier scenarios. Factorial analyses were conducted to identify intervention inputs with largest and smallest effects. As a base case with no precautions (or no compliance), predicted 16-week student infections and mortality under normal operations ranged significantly from 471 to 9,495 (median: 2,286, SD: 2,627) and 0 to 123 (median: 9, SD: 14) per 10,000 students, respectively. The maximum active exposures across a semester was 15.76% of all students warranting tracing. Total additional community exposures, infections, and mortality ranged from 1 to 187, 13 to 820, and 1 to 21 per 10,000 residents, respectively. 1% and 5% of on-campus students were infected after a mean (SD) of 11 (3) and 76 (17) days, respectively; >10% students infected by the end of a semester in 34.8% of scenarios, with the greatest increase (first inflection point) occurring on aver-age on day 84 (SD: 10.2 days). Common reopening precautions reduced infections by 24% to 26% and mortality by 36% to 50% in both populations. Uncertainties in many factors, however, produced tremendous variability in all results, ranging from medians by -67% to +342%. Consequences on community and student Covid-19 exposures, infections, and mortality of reopening physical campuses are very highly unpredictable, depending on a combination of random chance, controllable (e.g. physical layouts), and uncontrollable (e.g. human behavior) factors. Implications include needs for criteria to adapt campus operations mid-semester, methods to detect when necessary, and contingency plans for doing so.