Effects of lipopolysaccharide priming on acute ischemic brain injury.
Infection has been implicated as a stroke risk factor. Activation and infiltration of polymorphonuclear neutrophils (PMNs) after cerebral ischemia may contribute to ischemic brain injury. This study was conducted to investigate how enhanced postischemic PMN infiltration by lipopolysaccharide (LPS) altered the acute ischemic outcomes. LPS (0.05 mg/kg SC) or vehicle was given to Long-Evans male rats 24 hours before ischemia. Focal cerebral ischemia was induced by temporary ligation of the right middle cerebral artery and both common carotid arteries for 45 minutes. Animals were killed 6 and 24 hours after reperfusion to determine the extent of PMN infiltration (myeloperoxidase assay), brain edema (wet-dry weight method), and vascular injury (fluorescein isothiocyanate-conjugated dextran extravasation). The infarct volumes were measured on the basis of TTC stain 24 hours after ischemia. LPS had little effect on body temperature or peripheral white count but substantially enhanced PMN infiltration into the ischemic right middle cerebral artery cortex on the basis of myeloperoxidase activity (6 hours: control, 0 U/g; LPS, 0.186+/-0. 025 U/g; 24 hours: control, 0.185+/-0.025 U/g; LPS, 0.290+/-0.040 U/g; P<0.001) and morphological studies. The extent of vascular injury defined by the extravasation of fluorescein isothiocyanate-conjugated dextran into the ischemic tissue (6 hours: control, 3.11+/-0.41 microliter/mg protein; LPS, 0.48+/-0.16 microliter/mg protein; 24 hours: control, 1.77+/-0.23 microliter/mg protein; LPS, 0. 90+/-0.19 microliter/mg protein; P<0.001) and brain edema determined by the brain water content (6 hours: control, 84.77+/-1.63%; LPS, 82. 09+/-1.25%; 24 hours: control, 89.40+/-0.43%; LPS, 87.88+/-0.58%; P<0.01) were paradoxically reduced by LPS priming. LPS-primed rats also had smaller infarct volumes (control, 135+/-5 mm(3); LPS, 108+/-12 mm(3); P<0.05). Enhanced postischemic PMN infiltration is anticipated to facilitate ischemic brain injury. Contrary to this expectation, results from the present study suggest that an increase in postischemic PMN infiltration after LPS priming was not detrimental. These findings challenge the notion that postischemic PMN infiltration is uniformly deleterious.


Choice or no choice? The need for better branded public sector condoms in South Africa.
Condoms are one of the cornerstones to any response to the HIV epidemic. However, targeted marketing strategies that make condoms more attractive to people at high risk of infection are often overlooked. The South African National Department of Health has recently purchased more attractive condoms to distribute in higher-education settings free of charge, targeting at-risk youth including young women. The authors applaud this move but note the importance of expanding better branded condoms to young people elsewhere - for example, via youth clinics and in high schools. Exploratory, routine data from Médecins Sans Frontières in Khayelitsha are presented, showing the popularity of alternatives to the government's 'Choice' brand.


Near-Infrared-Controlled Nanoplatform Exploiting Photothermal Promotion of Peroxidase-like and OXD-like Activities for Potent Antibacterial and Anti-biofilm Therapies.
Nanozymes that mimic peroxidase (POD) activity can convert H2O2 into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WS2QDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WS2QDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WS2QDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WS2QDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate Staphylococcus aureus reference strain) and Gram-negative Escherichia coli and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. In vivo studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WS2QDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.


In vivo therapeutic efficacies of PD 138312 and PD 140248, two novel fluoronaphthyridines with outstanding gram-positive potency.
PD 138312 and PD 140248 are novel broad-spectrum 7-pyrrolidinyl fluoronaphthyridines with a cyclopropyl or a difluorophenyl substitution at the 1 positions, respectively. They have been demonstrated to have excellent in vitro activity against gram-positive organisms. These compounds were evaluated for their in vivo potencies against acute systemic infections in mice and in a mouse pneumococcal pneumonia model. They were very effective by both the oral and subcutaneous routes of administration. Most remarkable were their comparative median protective values against methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes. In general, these compounds were 28- to 100-fold more active than ciprofloxacin against these clinically significant organisms when the drugs were given orally and 10- to 38-fold more active when the drugs were given parenterally. Average ratios of drug concentrations in mice after drug administration by the oral route to that after administration by the subcutaneous route indicate 34 to 44% greater bioavailabilities of PD 138312 and PD 140248 compared with that of ciprofloxacin. In a multidose pneumococcal mouse pneumonia model these new quinolones were extremely effective, with median curative doses of 2 to 2.8 mg/kg of body weight per dose. Ciprofloxacin was ineffective (median curative dose, >100 mg/kg per dose) in this model. Comparative pharmacokinetic studies in mice revealed a relative superiority of PD 140248. Peak levels of PD 140248 in blood after the administration of a single oral 50-mg/kg dose were twice those of PD 138312 and ciprofloxacin, with PD 140248 having a substantially longer half-life. These results indicate that PD 138312 and PD 140248 have excellent therapeutic potential against clinically important gram-positive pathogens when the drugs are administered both orally and parenterally.


Suprasellar Clear Cell Meningioma in an Infant.
Clear cell meningiomas are an uncommon subtype of meningioma rarely seen in infancy. We report a case of clear cell meningioma in an 8-month-old male infant. He presented at the Lagos University Teaching Hospital, Lagos, Nigeria, in 2015 with persistent vomiting, poor feeding and failure to thrive over a four month period. Generalised hypertonia and hyperreflexia were noted on examination. Computed tomography of the brain revealed a huge largely isodense suprasellar mass with a hypodense core. The tumour, which measured 6 × 5 × 4 cm, enhanced non-uniformly with contrast injection and extended to occlude the third ventricle. The patient underwent a bifrontal craniotomy with subtotal tumour excision. Six hours postoperatively, he went into cardiac arrest and could not be resuscitated. A histological diagnosis of clear cell meningioma was made as the tumour cells were immunoreactive to epithelial membrane antigen, S100 protein and vimentin. This case of clear cell meningioma was unusual due to its early occurrence and supratentorial location.


Managing suicide risk in late life: access to firearms as a public health risk.
The authors assessed the prevalence of gun availability for elderly patients to determine whether gun availability is related to the presence of suicidal or depressive symptoms. This is a cross-sectional epidemiologic survey of firearm availability and safety practices. A random sample of older adults with a scheduled primary-care clinic appointment was selected and screened with the General Health Questionnaire and questions about suicidality and alcohol use. Participants were also asked about the availability of firearms in their home and about safe gun practices. Of 1,023 patients screened, 285 (27.9%) reported having some type of firearm in the home, and 202 (19.7%) reported having a handgun in the home. Patients with suicidal ideation or high levels of depression or psychological distress were not significantly more or less likely to have a gun in the home than those without these emotional stressors. The strongest predictors of firearm availability were being male and being married. These preliminary data suggest that a significant proportion of elderly people have firearms available to them in their homes. Those patients with emotional distress did not differ from those without distress with respect to having firearms available to them. These data strongly suggest the need for screening for firearm availability and education about the safe storage of firearms as a potential means of prevention of suicide among elderly patients suffering from emotional distress or suicidal ideation.


Atomic-Scale Control of Magnetism at the Titanite-Manganite Interfaces.
Complex oxide thin-film heterostructures often exhibit magnetic properties different from those known for bulk constituents. This is due to the altered local structural and electronic environment at the interfaces, which affects the exchange coupling and magnetic ordering. The emergent magnetism at oxide interfaces can be controlled by ferroelectric polarization and has a strong effect on spin-dependent transport properties of oxide heterostructures, including magnetic and ferroelectric tunnel junctions. Here, using prototype La2/3Sr1/3MnO3/BaTiO3 heterostructures, we demonstrate that ferroelectric polarization of BaTiO3 controls the orbital hybridization and magnetism at heterointerfaces. We observe changes in the enhanced orbital occupancy and significant charge redistribution across the heterointerfaces, affecting the spin and orbital magnetic moments of the interfacial Mn and Ti atoms. Importantly, we find that the exchange coupling between Mn and Ti atoms across the interface is tuned by ferroelectric polarization from ferromagnetic to antiferromagnetic. Our findings provide a viable route to electrically control complex magnetic configurations at artificial multiferroic interfaces, taking a step toward low-power spintronics.


Initial experiences regarding COVID19 mortality in Punjab-A mixed method analysis.
The spread of COVID-19 pandemic poses a great challenge to health care organizations and unprecedented need for information. This study aims to identify possible factors causing delay and losing precious time during diagnosis and treatment of COVID-19 at home and health facility level. It also aims to highlight perceptions and experiences of family members of deceased regarding diagnosis and treatment of COVID-19 infection in hospital. A retrospective study was done to review COVID-19 deaths from 18th March to 5th June 2020 in Punjab, India. A total of 48 laboratory confirmed (RT-PCR) COVID-19 deaths were reported during this period. Socio demographic profile, sequence of events including clinical symptoms, medical aid taken, time of confirmation of diagnosis and treatment before death were noted from the records on a predesigned proforma. Family members of deceased were also interviewed and asked open-ended questions regarding their experiences at various health facilities. Descriptive statistics was presented in percentages, mean, and median. Mean age of subjects was 56.3 ± 18.3 years. Majority (82.2%) had three or more than three comorbidities. Median time from appearance of first symptom to first medical contact and confirmation of diagnosis was 1 and 5 days, respectively. On the basis of interview with deceased's relative, various themes like delay in diagnosis and treatment, dissatisfied with hospital system and lack of communication between relative and patient were generated. Presence of comorbidities was the most important risk factor. Health seeking behavior of patients immediately after appearance of symptoms was found to be satisfactory.


Internalized Sexual Orientation Stigma and Mental Health in a Religiously Diverse Sample of Gay and Bisexual Men in Lebanon.
This study explores the correlates of internalized sexual orientation stigma, psychological distress and depression in a religiously diverse sample of gay and bisexual men in Lebanon. A convenience sample of 200 participants completed a cross-sectional survey. Bisexual men reported greater internalized sexual orientation stigma and less outness to their family and were more likely to face family pressure to have a heterosexual marriage than gay men. People of no religion reported more outness than Muslims and Christians but also higher psychological distress and depression. Multiple regression analyses showed that religiosity, outness, family pressure to marry and being bisexual were positively associated with internalized sexual orientation stigma; and that frequency of attending one's place of worship was negatively associated with psychological distress and depression. Individuals may be coping with adversity through engagement with institutionalized religion, which also appears to be a source of negative social representations concerning their sexuality.


Effect of fennel essential oil on performance, serum biochemistry, immunity, ileum morphology and microbial population, and meat quality of broiler chickens fed corn or wheat-based diet.
1. The effect of Foeniculi aetheroleum essential oil (EO) on growth performance, nutrient utilisation, serum biochemistry, immune response, ileum morphology, microbial population and meat quality of broiler chickens fed a corn- or wheat-based diet were determined.2. A total of 360 broiler chickens were arranged in a 2 × 2 factorial assay in a completely randomised design with six replicates and 15 birds per experimental unit. Birds were fed corn- or wheat-based diets supplemented with (200 mg/kg) or without fennel EO.3. Birds fed wheat-based diets had lower BWG and FCR during grower period and lower FI during finisher period as compared to those fed corn-based diet (P < 0.05) whereas addition of fennel EO decreased chickens BWG during finisher period and EPEF, both in wheat or in corn-based diets. Dietary treatments had no effect on serum glucose, triglyceride, cholesterol, LDL-cholesterol, AST, ALT, ALP, and MDA concentrations (P < 0.05).4. Antibody titres against avian influenza and sheep red blood cell antibody titres, crude protein and crude fat utilisation, villus height, crypt depth and epithelium thickness were not influenced by dietary treatments (P > 0.05). Inclusion of Fennel EO to the corn-based diet resulted in greater villus width and villus surface area while it reduced lamina propria thickness (P < 0.05). Fennel EO reduced ileal E. coli and Lactobacillus spp. populations (P < 0.05). Dietary treatments had no significant effect on meat pH, cooking loss, drip loss, crude protein, crude fat content and cholesterol concentration of breast and thigh meat, total phenolic and MDA concentrations, and breast meat sensory parameters (P > 0.05).5. These results showed that addition of fennel EO to wheat-based diets had a negative effect on chicken growth performance variables and decreased gut E. coli populations. However, immunity, meat quality and nutrient utilisation were not affected by dietary treatments.


Factors in the reproducibility of electromyographic power spectrum analysis of lumbar paraspinal muscle fatigue.
An investigation of the reliability of various factors used to analyze electromyograms of paraspinal muscles of the lumbar spine. To determine the reproducibility of several electromyographic variables over time and to assess the influence of confounding factors. Previous reliability studies have included small numbers of subjects and often have not explored the factors that can influence the reliability of this technique. In the first study, 39 volunteers underwent electromyographic tests on three occasions at two loads. The time interval was 1 week between tests. Electromyographic variables measured included half-width (spectral width at half maximum amplitude), initial median frequency, median frequency slope, initial root mean square, root mean square, and root mean square slope. In the second study to determine the influence of posture, nine volunteers were tested on two occasions with a change in posture between tests. Reliability was better for tests at the higher loads. Initial median frequency, half-width, and root mean square all had acceptable reproducibility over time, with a coefficient of variation less than 10. Initial median frequency and half-width proved to be the most suitable variables; they yielded the largest between-subject variation and, of all variables, were affected the least by changes in load. The remaining variables were very load-dependent. A change in posture greatly influenced the reproducibility. These results demonstrate that only initial median frequency and half-width have acceptable reproducibility over time and at different loads, with the potential to be useful in discriminating between individuals. Changes in posture can greatly change an electromyographic result.


Corrosion resistance of stainless steel, nickel-titanium, titanium molybdenum alloy, and ion-implanted titanium molybdenum alloy archwires in acidic fluoride-containing artificial saliva: An in vitro study.
(1) To evaluate the corrosion resistance of four different orthodontic archwires and to determine the effect of 0.5% NaF (simulating high fluoride-containing toothpaste of about 2250 ppm) on corrosion resistance of these archwires. (2) To assess whether surface roughness (Ra) is the primary factor influencing the corrosion resistance of these archwires. Four different archwires (stainless steel [SS], nickel-titanium [NiTi], titanium molybdenum alloy [TMA], and ion-implanted TMA) were considered for this study. Surface characteristics were analyzed using scanning electron microscopy, atomic force microscopy (AFM), and energy dispersive spectroscopy. Linear polarization test, a fast electrochemical technique, was used to evaluate the corrosion resistance, in terms of polarization resistance of four different archwires in artificial saliva with NaF concentrations of 0% and 0.5%. Statistical analysis was performed by one-way analysis of variance. The potentiostatic study reveals that the corrosion resistance of low-friction TMA (L-TMA) > TMA > NiTi > SS. AFM analysis showed the surface Ra of TMA > NiTi > L-TMA > SS. This indicates that the chemical composition of the wire is the primary influential factor to have high corrosion resistance and surface Ra is only secondary. The corrosion resistance of all wires had reduced significantly in 0.5% acidic fluoride-containing artificial saliva due to formation of fluoride complex compound. The presence of 0.5% NaF in artificial saliva was detrimental to the corrosion resistance of the orthodontic archwires. Therefore, complete removal of residual high-fluorinated toothpastes from the crevice between archwire and bracket during tooth brushing is mandatory.


Metabolism and translocation of allantoin in ureide-producing grain legumes.
Transfer of the nitrogen and carbon of allantoin to amino acids and protein of leaflets, stems and petioles, apices, peduncles, pods, and seeds of detached shoots of nodulated cowpea (Vigna unguiculata L. Walp. cv. Caloona) plants was demonstrated following supply of [2-(14)C], [1,3-(15)N]allantoin in the transpiration stream. Throughout vegetative and reproductive growth all plant organs showed significant ureolytic activity and readily metabolized [2-(14)C]allantoin to (14)CO(2). A metabolic pathway for ureide nitrogen utilization via allantoic acid, urea, and ammonia was indicated. Levels of ureolytic activity in extracts from leaves and roots of nodulated cowpea were consistently maintained at higher levels than in non-nodulated, NO(3) (-) grown plants.[(14)C]Ureides were recovered in extracts of aphids (Aphis craccivora and Macrosiphum euphorbieae) feeding at different sites on cowpea plants supplied with [2-(14)C]allantoin through the transpiration stream or to the upper surface of single leaflets. The data indicated that the ureides were effectively transferred from xylem or leaf mesophyll to phloem, and then translocated in phloem to fruits, apices, and roots.


Antibacterial effects of carbon monoxide.
Carbon monoxide (CO) is a colourless and odourless gas that has long been considered as a potent respiratory poison. Recent advances have demonstrated its production by haem oxygenases in both mammals and microbes, and it has roles as a gasotransmitter in higher organisms. This review concentrates on the application of CO, via carbon monoxide-releasing molecules (CO-RMs), as an anti-bacterial agent. Currently, the scope of literature on the effects of CO on bacteria is small, and we have included discussions on the production of CO by bacteria via haem oxygenase enzymes, the use of CO as an energy source, and existing knowledge on CO sensors in bacteria. CO is known to target haem proteins and is an effective inhibitor of respiration, even when provided at concentrations much higher than prevailing oxygen. We review here data suggesting that CO-RMs are more effective inhibitors of respiration than is CO gas, perhaps due to the ability of CO-RMs to deliver CO selectively to intracellular targets. We also consider the recently reported transcriptomic consequences of CO-RM treatment of Escherichia coli, revealing a myriad of unexpected targets for CO and potential CO sensors. Finally, we consider the use of CO and CO-RMs as anti-bacterial agents in vivo, and the future prospects for this gaseous molecule.


[Comparative analysis of mono- and bipolar pyramidal tract mapping in patients with supratentorial tumors adjacent to motor areas: comparison of data at 64 stimulation points].
To compare monopolar and bipolar mapping in point-by-point fashion by using of threshold amperage, frequency of positive motor responses and the number of muscles involved in response. A prospective non-randomized study included 14 patients with supratentorial tumors who underwent surgery in 2018-2019. All neoplasms were localized within 2 cm from the motor cortex and pyramidal tract. Age of patients ranged from 25 to 74 years. There were 9 women and 5 men. Eight patients had malignant glioma (grade III - 4, grade IV - 4), 6 patients - meningioma. Motor functions were assessed in all patients before and after surgery (1, 7 days and 3 months later) by using of a 5-point scale. In addition to routine neurophysiological monitoring, comparative mono- and bipolar mapping of the pyramidal tract within the bed of excised tumor was carried out at the end of surgery. The points of motor responses were marked. Comparative analysis of mono- and bipolar stimulation at identical points included threshold amperage, frequency of positive motor responses and the number of muscles involved in response (leg, forearm, hand, facial muscles). Brain MRI was performed in early postoperative period for assessment of resection quality. There were 64 points of motor responses in 14 patients. The number of these points ranged from 2 to 8 per a patient (mean 5 points). Motor responses were recorded in 57 points during monopolar and bipolar stimulation, in other 7 points - only during monopolar stimulation. Amperage of monopolar stimulation was 3-15 mA, bipolar stimulation - 2.5-25 mA. Threshold amperage (7.37 mA for monopolar stimulation and 8.88 mA for bipolar stimulation; p=0.12), frequency of positive motor responses and the number of muscles involved in response (p=0.1 and p=0.73) were similar. Seven (50%) patients had neurological deterioration in early postoperative period (4 patients with glial tumors and 3 patients with meningiomas). At the same time, only 2 patients (14.3%) had persistent neurological deficit (both patients with infiltrative meningioma). According to postoperative MRI in T1+C mode, resection volume was 100% in 1 patient with contrast-enhanced glioma and 94% in another one. According to FLAIR MRI data, resection volume exceeded 70% in 2 patients with non-enhancing glioma and less than 70% in 2 patients. Meningioma resection volume was estimated according to postoperative T1+C MRI data and made up over 90% in 4 patients. Monopolar stimulation is a reliable method of pyramidal tract identification in supratentorial brain tumor surgery.


Primary lung adenocarcinomas in children and adolescents treated for pediatric malignancies.
Primary lung adenocarcinoma is extremely rare in the pediatric age group. There have been anecdotal reports of lesions that are histologically indistinguishable from adult-type pulmonary adenocarcinoma in young patients after treatment for nonpulmonary cancers. Herein, we present clinical, histopathologic, and molecular data on eight such cases. Histopathologic evaluation of the tumors was performed according to the World Health Organization classification. Molecular studies for EGFR and KRAS mutations were performed on six patients with sufficient material. All eight patients were never smokers, four males and four females. Median age at nonpulmonary cancer diagnosis was 14 years (range, 3-23 years). Pulmonary adenocarcinomas were diagnosed at a median age of 15 years (range, 10-24 years); tumors were 0.1 to 2.0 cm in size and in some cases coexisted with metastases from the original cancer. Retrospective review showed that in at least three patients, the nodules were radiographically present before chemotherapy. Of six patients whose tumors were tested for common EGFR and KRAS mutations, two were positive for the former and one for the latter. At a median follow-up of 11 months (range, 2-29 months), six patients remained well without lung nodules and two had additional small, peripheral lung nodules that have not been biopsied. Pulmonary lesions found in young patients with pediatric cancers can be histologically indistinguishable from lung adenocarcinoma seen in adults, may display typical adenocarcinoma-associated mutations of EGFR and KRAS, and may precede the administration of cytotoxic chemotherapy.


Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary inflammation and injury in mice with sickle cell disease.
We showed previously that pulmonary function and arterial oxygen saturation in NY1DD mice with sickle cell disease (SCD) are improved by depletion of invariant natural killer T (iNKT) cells or blockade of their activation. Here we demonstrate that SCD causes a 9- and 6-fold induction of adenosine A(2A) receptor (A(2A)R) mRNA in mouse pulmonary iNKT and natural killer (NK) cells, respectively. Treating SCD mice with the A(2A)R agonist ATL146e produced a dose-dependent reversal of pulmonary dysfunction with maximal efficacy at 10 ng/kg/minute that peaked within 3 days and persisted throughout 7 days of continuous infusion. Crossing NY1DD mice with Rag1(-/-) mice reduced pulmonary injury that was restored by adoptive transfer of 10(6) purified iNKT cells. Reconstituted injury was reversed by ATL146e unless the adoptively transferred iNKT cells were pretreated with the A(2A)R alkylating antagonist, FSPTP (5-amino-7-[2-(4-fluorosulfonyl)phenylethyl]-2-(2-furyl)-pryazolo[4,3-ε]-1,2,4-triazolo[1,5-c]pyrimidine), which completely prevented pro-tection. In NY1DD mice exposed to hypoxia-reoxygenation, treatment with ATL146e at the start of reoxygenation prevented further lung injury. Together, these data indicate that activation of induced A(2A)Rs on iNKT and NK cells in SCD mice is sufficient to improve baseline pulmonary function and prevent hypoxia-reoxygenation-induced exacerbation of pulmonary injury. A(2A) agonists have promise for treating diseases associated with iNKT or NK cell activation.


How to avoid a HIPAA horror story.
The Health Information Technology for Economic and Clinical Health Act of 2009 significantly expands the financial risk of violations of the Health Insurance Portability and Accountability Act (HIPAA) and extends HIPAA procedures and penalties to business associates. Hospitals, physicians, and their business associates should ensure that HIPAA privacy and security provisions are adopted. Compliance efforts should focus on high-risk areas, including information access management, access control, and impermissible disclosures of protected health information.


A Rho kinase/myocardin-related transcription factor-A-dependent mechanism underlies the sphingosylphosphorylcholine-induced differentiation of mesenchymal stem cells into contractile smooth muscle cells.
Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hADSCs) to smooth muscle cells (SMCs). In the present study, we characterized contractile and ion channel properties of SMCs differentiated from hADSCs (hADSC-SMCs) as a result of SPC treatment, and we investigated the molecular mechanisms involved in the SPC-induced differentiation. Using in vitro collagen gel lattice contraction and whole cell patch clamp, we showed that the hADSC-SMCs expressed functional L-type voltage-gated Ca2+ channels and contractile activities in response to KCl, carbachol, and the L-type Ca2+ channel opener Bay K8644, whereas the L-type Ca2+ channel blocker nifedipine abrogated the contractility of hADSC-SMCs. Furthermore, hADSC-SMCs expressed functional big conductance Ca2+-activated K+ (BK(Ca)) channels, and the BK(Ca) channel blocker iberiotoxin potentiated the Bay K8644-stimulated contractility of the hADSC-SMCs, indicating that these cells exhibited SMC-like contractile characteristics. SPC activated RhoA in hADSCs and pretreatment with the Rho kinase inhibitor Y27632 or by overexpression of dominant-negative mutants of RhoA or Rho kinase completely abrogated the SPC-induced differentiation of hADSCs into SMCs. SPC also increased the expression levels of myocardin-related transcription factor (MRTF)-A, a transcription factor involved in smooth muscle differentiation, in hADSCs. Small interference RNA-mediated depletion of endogenous MRTF-A abolished the SPC-induced differentiation of hADSCs into SMCs. Furthermore, SPC promoted nuclear translocation of MRTF-A, and pharmacological inhibition of Rho kinase blocked this effect. These results suggest that SPC induced differentiation of hADSCs into contractile SMCs through a mechanism involving RhoA/Rho kinase-dependent nuclear translocation of MRTF-A.


Interoception visualization relieves acute pain.
Interoception is the sensation of the physiological state inside one's body. Growing evidence suggests that visual feedback of interoception improves body self-consciousness (BSC) and reduces pain perception among patients with chronic pain. However, whether the integration of exteroception and interoception influences pain processing in healthy individuals remains largely unknown. To examine this question, we combined the rubber hand illusion (RHI) paradigm with visualized interoception -flashing of an LED light on the rubber hand synchronously or asynchronously with participants' real-time heartbeats. Under these conditions, we tested pain thresholds and corresponding event-related potentials. The interoceptive visual feedback inhibited the P2 component of pain, and the RHI inhibited pre-stimulus alpha-band brain activity. BSC had no significant effect on the processing of pain. These findings demonstrate that interoceptive signals with visual feedback inhibit pain processing, and that this psychophysiological process is largely independent of reported self-consciousness, in healthy individuals.


Prevalence and factors associated with demoralization in palliative care patients: A cross-sectional study from Hong Kong.
Although demoralization is common among palliative care patients, it has not yet been examined empirically in the Hong Kong Chinese context. This study aims to examine (1) the prevalence of demoralization among community-dwelling palliative care patients in Hong Kong; (2) the percentage of palliative care patients who are demoralized but not depressed and vice versa; and (3) the association of socio-demographic factors, particularly family support, with demoralization. A cross-sectional study targeting community-living palliative care patients in Hong Kong was conducted. A total of 54 patients were recruited by a local hospice and interviewed for completing a questionnaire which included measures of demoralization, depression, perceived family support, and demographic information. The prevalence of demoralization was 64.8%. Although there was overlap between demoralization and depression (52.8% meeting the criteria of both), 7.5% of depressed patients were not demoralized, and 13.2% of demoralized patients were not depressed. Participants who were not single and had more depressive symptoms and less family support had a significantly higher demoralization level. This is the first study which reports the prevalence of demoralization in Hong Kong. Demoralization was found common in community-living palliative care patients receiving medical social work services in Hong Kong. This study provides evidence of the importance of differentiating the constructs between demoralization and depression. It also provides an implication that those who are married, more depressed, and have the least family support could be the most vulnerable group at risk of demoralization. We recommend that early assessment of demoralization among palliative care patients be considered.


Behavior of trypsin and related enzymes toward amidinophenyl esters.
Kinetics of the hydrolysis of amidinophenyl esters catalyzed by urokinase, kallikrein, plasmin and trypsins from various origins were studied. P-Amidinophenyl esters in which the arrangement of the specific group for bovine trypsin (charged amidinium) is reversed to that of normal substrates were characterized as specific substrates for the enzyme and named "inverse substrates" (K. Tanizawa, Y. Kasaba and Y. Kanaoka, J. Am. Chem. Sc., 99, 4485-4488) Behavior of these enzymes toward amidinophenyl esters was demonstrated to be very similar to that of bovine trypsin. These observations account for the structural similarity of their active sites. p- Amidinophenyl esters were found to be hydrolyzed also by clostripain which is known as a thiol protease with trypsin-like specificity. This is the first example of the "inverse substrates" for a thiol enzyme.


Matriptase-2 gene (TMPRSS6) variants associate with breast cancer survival, and reduced expression is related to triple-negative breast cancer.
Matriptase-2 (TMPRSS6) has been identified as a breast cancer risk factor. Here, we examined relationships between TMPRSS6 genetic variations and breast cancer risk and survival, and determined the gene and protein expressions in breast tumors and assessed their clinical importance. Thirteen TMPRSS6 polymorphisms were genotyped in 462 invasive breast cancer cases and 458 controls. Gene expression was analyzed from 83 tumors and protein expression from 370 tumors. We then assessed the statistical significance of associations among genotypes, clinicopathological characteristics and survival. The TMPRSS6 variant rs2543519 was associated with breast cancer risk (p = 0.032). Multivariate analysis showed that four variants had effects on survival-rs2543519 (p = 0.017), rs2235324 (p = 0.038), rs14213212 (p = 0.044) and rs733655 (p = 0.021)-which were used to create a group variable that was associated with poorer prognosis correlating with more alleles related to reduced survival (p = 0.006; risk ratio, 2.375; 95% confidence interval, 1.287-4.382). Low gene expression was related to triple-negative breast cancer (p = 0.0001), and lower protein expression was detected in undifferentiated (p = 0.019), large (p = 0.014) and ductal or lobular tumors (p = 0.036). These results confirm the association of TMRRSS6 variants with breast cancer risk and survival. Matriptase-2 levels decrease with tumor progression, and lower gene expression is seen in poor-prognosis-related triple-negative breast cancers. Our study is the first to show that matriptase-2 gene variants are related to breast cancer prognosis, supporting matriptase-2 involvement in tumor development.


Extrusion printing for fabrication of spherical and cylindrical microlens arrays.
In this paper, we present an extrusion printing technique for producing spherical and cylindrical plano-convex microlens arrays with controllable feature dimensions. This technique employs a robotic adhesive dispenser for robotically controlled microextrusion of ultraviolet (UV) curable polymer onto a glass substrate surface to directly deposit the microlens arrays. It provides a simple and flexible alternative to fabricate both spherical and cylindrical microlens arrays.


The Slowing Rate of CpG Depletion in SARS-CoV-2 Genomes Is Consistent with Adaptations to the Human Host.
Depletion of CpG dinucleotides in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes has been linked to virus evolution, host-switching, virus replication, and innate immune responses. Temporal variations, if any, in the rate of CpG depletion during virus evolution in the host remain poorly understood. Here, we analyzed the CpG content of over 1.4 million full-length SARS-CoV-2 genomes representing over 170 million documented infections during the first 17 months of the pandemic. Our findings suggest that the extent of CpG depletion in SARS-CoV-2 genomes is modest. Interestingly, the rate of CpG depletion is highest during early evolution in humans and it gradually tapers off, almost reaching an equilibrium; this is consistent with adaptations to the human host. Furthermore, within the coding regions, CpG depletion occurs predominantly at codon positions 2-3 and 3-1. Loss of ZAP (Zinc-finger antiviral protein)-binding motifs in SARS-CoV-2 genomes is primarily driven by the loss of the terminal CpG within the motifs. Nonetheless, majority of the CpG depletion in SARS-CoV-2 genomes occurs outside ZAP-binding motifs. SARS-CoV-2 genomes selectively lose CpGs-motifs from a U-rich context; this may help avoid immune recognition by TLR7. SARS-CoV-2 alpha-, beta-, and delta-variants of concern have reduced CpG content compared to sequences from the beginning of the pandemic. In sum, we provide evidence that the rate of CpG depletion in virus genomes is not uniform and it greatly varies over time and during adaptations to the host. This work highlights how temporal variations in selection pressures during virus adaption may impact the rate and the extent of CpG depletion in virus genomes.


Potential use of glucuronylglucosyl-β-cyclodextrin/dendrimer conjugate (G2) as a DNA carrier in vitro and in vivo.
In this study, we evaluated the polyamidoamine starburst dendrimer (dendrimer, generation 2: G2) conjugate with 6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-β-cyclodextrin (GUG-β-CDE (G2)) as a gene transfer carrier. The in vitro gene transfer activity of GUG-β-CDE (G2, degree of substitution (DS) of cyclodextrin (CyD) 1.8) was remarkably higher than that of dendrimer (G2) conjugate with α-CyD (α-CDE (G2, DS 1.2)) and that with β-CyD(β-CDE (G2, DS 1.3)) in A549 and RAW264.7 cells. The particle size, ζ-potential, DNase I-catalyzed degradation, and cellular association of plasmid DNA (pDNA) complex with GUG-β-CDE (G2, DS 1.8) were almost the same as those of the other CDEs. Fluorescent-labeled GUG-β-CDE (G2, DS 1.8) localized in the nucleus 6 h after transfection of its pDNA complex in A549 cells, suggesting that nuclear localization of pDNA complex with GUG-β-CDE (G2, DS 1.8), at least in part, contributes to its high gene transfer activity. GUG-β-CDE (G2, DS 1.8) provided higher gene transfer activity than α-CDE (G2, DS 1.2) and β-CDE (G2, DS 1.3) in kidney with negligible changes in blood chemistry values 12 h after intravenous injection of pDNA complexes with GUG-β-CDE (G2, DS 1.8) in mice. In conclusion, the present findings suggest that GUG-β-CDE (G2, DS 1.8) has the potential for a novel polymeric pDNA carrier in vitro and in vivo.


[Electricity generation from corn steepwater using microbial fuel cell technology].
Corn steepwater containing 49,732.2 mg/L of chemical oxygen demand (COD) was used as fuel for a membrane electrode assembly microbial fuel cell (MEA-MFC), which could generate electricity and treat the wastewater at the same time. During a batch experiment of 94 days with a fixed 1,000 Omega external resistance, the maximum voltage output of 525.0 mV and power density of 169.6 mW/m2 were obtained after 17 days, corresponding to the current density, internal resistance and open voltage of 440.2 mA/m2, 350 Omega and 619.5 mV, respectively. However, data showed that the coulombic efficiency was only 1.6%, suggesting very limited COD was utilized for electricity generation. At the conclusion of the test, the removals of COD and ammonia-nitrogen were achieved 51.6% and 25.8%, respectively. This study demonstrates that corn steepwater can be used for power generation in MFC with simultaneous accomplishments of wastewater treatment, providing a novel approach for the safe disposal and recycle of corn steepwater.


Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease.
The aim of the study was the evaluation of serum vitamin B12 and folate levels in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and their association with the disease severity. Thirty patients with biopsy-proven NAFLD and 24 healthy controls matched for gender, age, body mass index and waist circumference were recruited. Blood samples for vitamin B12, folate, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance was calculated. There was no difference in serum vitamin B12 and folate levels between groups. Neither vitamin B12 nor folate levels were significantly different within any histological category, including steatosis grade, fibrosis stage, lobular inflammation, portal inflammation and ballooning. In conclusion, similar vitamin B12 and folate levels were observed in non-alcoholic steatohepatitis and non-alcoholic fatty liver patients, and controls. Furthermore, vitamin B12 and folate levels were not associated with either insulin resistance or the severity of liver disease.


Risk factors and management of patients with upper limb deep vein thrombosis.
To determine the prevalence of endogenous and exogenous risk factors for venous thrombosis in patients with upper limb deep vein thrombosis (DVT), and to evaluate the risk of clinically detectable pulmonary embolus, recurrent DVT, and postphlebitic symptoms in these patients. A combined prospective and retrospective descriptive analysis of a cohort of patients with upper limb DVT compared with age- and sex-matched patients with lower limb DVT. Internal medicine departments, and hematology and vascular surgery outpatient clinics at a tertiary-care university hospital. Consecutive patients with "spontaneous" upper limb DVT diagnosed between 1989 and 1997 were studied. Twenty age- and sex-matched patients with lower limb DVT admitted to the hospital via the emergency department served as control patients. Eighteen patients with upper limb DVT were studied. An endogenous risk factor (thrombophilia) was present in 11 of 18 patients vs 8 of 20 control patients (p = not significant). In the upper limb group, nine patients had activated protein C resistance, four patients had anticardiolipin antibodies, and two patients had both forms of thrombophilia. Furthermore, 14 of the upper limb DVT patients were found to have an exogenous risk factor for thrombosis compared with 7 of the patients with lower limb DVT (p = 0.01), and 66.6% of patients with upper limb DVT had both an exogenous and an endogenous risk factor for thrombosis vs 15% of patients with lower limb DVT (p < 0.002). No clinically detectable pulmonary emboli occurred among the upper limb DVT patients. Three patients have minor postphlebitic symptoms. Two patients experienced recurrent DVT. In the majority of patients with upper limb DVT that we studied in this relatively small study, exogenous (environmental) or endogenous risk factors for venous thrombosis, or a combination of both, were found. Furthermore, in our patients, these thromboses had a low propensity to cause clinically significant pulmonary embolus and did not cause significant postphlebitic symptoms. Finally, we suggest that anticoagulant therapy for these thromboses may be adequate and that thrombolytic agents and surgical intervention are not routinely indicated.


Ulcerative tracheobronchitis due to Aspergillus.
Aspergillus ulcerative tracheobronchitis is a life-threatening form of invasive aspergillosis and is seldom seen in patients without underlying an immunocompromised state. Bronchoscopists must be familiar with this entity and consider Aspergillus ulcerative tracheobronchitis whenever mucosal erosions are seen, especially when unconventional risk factors such as intensive care unit admission and short-term glucocorticoid therapy are present. We present a case of invasive Aspergillus causing widespread ulcerative tracheobronchitis in a 39-year-old man with an asthma exacerbation requiring intensive care unit admission.


Nitrous oxide for pain management during in-office hysteroscopic sterilization: a randomized controlled trial.
To evaluate whether inhaled nitrous oxide with oxygen (N2O/O2) is associated with less pain compared to oral sedation for pain management during in-office hysteroscopic sterilization. This double blinded randomized controlled trial enrolled women undergoing in-office hysteroscopic sterilization. All participants received pre-procedure intramuscular ketorolac and a standardized paracervical block. The intervention group also received N2O/O2 via a nasal mask titrated to a maximum 70%:30% mixture by a nurse during the procedure and placebo pills pre-procedure and the active control group received inhaled O2 during the procedure and 5/325 mg hydrocodone/acetaminophen and 1 mg lorazepam pre-procedure. The primary outcome was maximum procedure pain on a 100 mm Visual Analog Scale (VAS with anchors at 0=no pain and 100=worst imaginable pain) assessed 3-5 min post procedure. Thirty women per treatment arm were required to detect a clinically significant pain difference of 20 mm. Seventy-two women, 36 per study arm, were randomized. Mean age of participants was 34.1±5.7 years and mean BMI was 30.1±6.6kg/m2. Mean maximum procedure pain scores were 22.8±27.6 mm and 54.5±32.7 mm for intervention and control groups, respectively (p<.001). Most study participants (97%) stated N2O/O2 should be offered for gynecologic office procedures and 86% would pay for it if not a covered benefit. N2O/O2 decreased pain with in-office hysteroscopic sterilization compared to oral sedation and is an effective pain management option for this procedure. Given its safety and favorable side effect profile, N2O/O2 can be used for pain management for in-office hysteroscopic sterilization and adds a safe, easily administered option to currently available strategies.


Histophotometry of protein thiols and disulphides in tissue samples from the human uterine cervix and the skin reveals a "field effect" as well as an "extended field effect" of malignant tumours.
Fresh frozen and fixed serial sections were stained with 2,2'-dihydroxy-6,6'-dinaphthyldisulfide (DDD) and Fast blue B for reactive protein thiols (PSHr) and total reactive protein sulfur (TRPS). The mean optical densities of PSHr and TRPS determined histophotometrically at a distinct part of a tissue were related to each other (PSHr: TRPS). If this quotient has been determined, e.g. for normal epithelium and the adjacent stroma, both quotients can be related to each other by a double quotient (Q PSHr: TRPS). With the aid of the double quotient highly significant differences could be found between tumours and normal tissue from patients without tumour of the human uterine cervix. Similar differences exist between normal skin from healthy patients and skin tumours. Q PSHr: TRPS revealed similar differences to exist between normal tissue of patients without tumour and apparently normal tissue in the neighbourhood of tumours of the uterine cervix and of skin ("field effect" of tumours). Histophotometric investigations on abdominal skin (and skin of breast) showed highly significant differences between normal skin of patients without tumour and patients with various kinds of tumours of the uterine cervix, ovaries, liver and breast ("extended field effect" of tumours).


First case report of an adrenocortical carcinoma caused by a BRCA2 mutation.
Adrenocortical carcinoma (ACC) may rarely be a component of inherited cancer syndromes such as Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome. ACC caused by a BRCA2 mutation has never been reported. Nucleotide sequencing of BRCA2 in lymphocyte and tumoral DNA of a 50-year-old male who presented with an androgen-secreting ACC and a strong family history of breast, ovarian, and pancreatic cancers. A germline BRCA2 2 bp heterozygous deletion at nucleotide 8765 (8765delAG) leading to a frameshift mutation (p.Glu2846GlyfsX23) was detected. Only the BRCA2 deleted allele was retained in the ACC tumoral DNA compared with the control DNA supporting a loss of heterozygosity in the tumor. This is the first reported case of a patient with ACC associated with a BRCA2 germline mutation. Loss of heterozygosity in ACC DNA suggests a causal link with the BRCA2 8765delAG mutation.


Machine Learning for Predicting the Risk for Childhood Asthma Using Prenatal, Perinatal, Postnatal and Environmental Factors.
The prevalence rate for childhood asthma and its associated risk factors vary significantly across countries and regions. In the case of Morocco, the scarcity of available medical data makes scientific research on diseases such as asthma very challenging. In this paper, we build machine learning models to predict the occurrence of childhood asthma using data from a prospective study of 202 children with and without asthma. The association between different factors and asthma diagnosis is first assessed using a Chi-squared test. Then, predictive models such as logistic regression analysis, decision trees, random forest and support vector machine are used to explore the relationship between childhood asthma and the various risk factors. First, data were pre-processed using a Chi-squared feature selection, 19 out of the 36 factors were found to be significantly associated (p-value < 0.05) with childhood asthma; these include: history of atopic diseases in the family, presence of mites, cold air, strong odors and mold in the child's environment, mode of birth, breastfeeding and early life habits and exposures. For asthma prediction, random forest yielded the best predictive performance (accuracy = 84.9%), followed by logistic regression (accuracy = 82.57%), support vector machine (accuracy = 82.5%) and decision trees (accuracy = 75.19%). The decision tree model has the advantage of being easily interpreted. This study identified important maternal and prenatal risk factors for childhood asthma, the majority of which are avoidable. Appropriate steps are needed to raise awareness about the prenatal risk factors.


[Behavior problems in language-impaired children: therapy evaluation using child behavior checklist].
Speech and language impaired children often show accompanying behavioral and emotional problems, putting an additional burden on their developmental course. In a sample of 57 children with a specific speech and language disorder we evaluated the behavioral changes after therapeutic intervention. The children got intensive treatment for about 15 months. Before the beginning of the treatment, all children were assessed using clinical psychiatric interviews and observations and were diagnosed according to the multiaxial classification scheme. The CBCL was filled in by the same parent before and after the treatment program. The Total Behavior Problem Score was used to assess changes in behavioral problems. The school type as well as the still necessary therapeutic interventions after the completion of the treatment program were used as global measures of psychosocial adaptation. 45 of 57 children had a psychiatric diagnosis on axis 1 of the multiaxial classification scheme. Hyperkinetic disorder, with or without conduct disorders were the most commonly given diagnoses, in addition to emotional disorders and adjustment problems. Before treatment, the children with a psychiatric diagnosis had higher scores on the Total Behavior Problem Score than the children without a psychiatric diagnosis. The children with psychiatric problems showed a significant decrease in the Total Behavior Problem Score of the CBCL. Although the children with a conduct disorder also showed improvement after treatment, their CBCL scores remained high. The stability of their problems was associated with a worse school prognosis and with further institutional care after the end of the treatment.


Age-related sympathetic ganglionic neuropathology: human pathology and animal models.
Systematic studies of the autonomic nervous system of human subjects and development of well-defined animal models have begun to substantially improve our understanding of the pathogenesis of autonomic dysfunction in aging and may eventually provide strategies for intervention. Neuropathological studies of the sympathetic ganglia of aged human subjects and rodent models have demonstrated that neuroaxonal dystrophy involving intraganglionic terminal axons and synapses is a robust, unequivocal and consistent neuropathological finding in the aged sympathetic nervous system of man and animals. Quantitative studies have demonstrated that markedly swollen argyrophilic dystrophic axon terminals develop in the prevertebral superior mesenteric (SMG) and coeliac, but to a much lesser degree in the superior cervical ganglia (SCG) as a function of age, sex (males more than females) and diabetes. Dystrophic axons were immunoreactive for neuropeptide Y, tyrosine hydroxylase, dopamine-beta-hydroxylase, trkA and p75NTR, an immunophenotype consistent with their origin from postganglionic sympathetic neurons, and contained large numbers of highly phosphorylated neurofilaments or tubulovesicular elements. The sympathetic ganglia of aged rodents also showed the hallmark changes of neuroaxonal dystrophy as a function of age and location (many more in the SMG than in the SCG). Plasticity-related synaptic remodeling could represent a highly vulnerable target of the aging process. The fidelity of animal models to the neuropathology of aged humans suggests that similar pathogenetic mechanisms may be involved in both and that therapeutic advances in animal studies may have human application.


Onchocerca spp: a "family" of secreted acidic proteins expressed by infective larvae in blackflies.
Biosynthetic labeling of developing larvae of Onchocerca in blackflies has been used to characterize a group of stage-specific, secreted proteins produced by vector-stage parasites. These are highly acidic molecules (pI 4.4-5.1) present in at least three members of the genus (O. volvulus, O. lienalis, O. ochengi) that exhibit minor heterogeneity among species in apparent molecular mass (between 18 and 23 kDa). In O. volvulus, there are two polypeptides that run as a doublet of 18 and 20 kDa. In O. lienalis and O. ochengi, single polypeptides of 23 and 20 kDa were detected. The processes of synthesis and secretion appear to be temperature-sensitive and dissociated events. Experiments with O. volvulus in Simulium damnosum sl revealed that synthesis is initiated in second stage larvae and increases in infective-stage parasites: Secretion occurs when larvae leave the vector and enter the phase of development associated with the vertebrate host. Third-stage larvae of O. lienalis were shown to continue to express and accumulate the 23-kDa protein with age. The primary organ of secretion, as indicated by dissection, was the glandular esophagus. These data point to an important biological role for this group of molecules and suggest that they may belong to a family of related products. Because they have the distinctive characteristics of being secreted larval acidic proteins, we propose the acronym SLAP pending further insights into their functional properties.


[Effects of applying different kind fertilizers on enzyme activities related to carbon, nitrogen, and phosphorus cycles in reddish paddy soil].
Based on the long-term fixed position experimental data from Qianyanzhou Ecological Experiment Station, Chinese Academy of Sciences in 1998, this paper analyzed the effects of applying different kind fertilizers (straw, ST; pig manure, OM; and chemical fertilizer, NPK) on the nutrients (C, N, and P) status and the activities of related enzymes ( beta-1,4-glucosidase, betaG; beta-1,4-N-acetylglucosaminidase, NAG; L-leucine aminopeptidase, LAP; and acid phosphatase, AP) in reddish paddy soil. With the application of OM, the activities of soil betaG, NAG, and LAP increased significantly, as compared with other treatments, and were 1.4, 2. 6, and 1.9 times higher than the control (CK) , respectively. Applying OM also improved the ratio of soil organic carbon to total nitrogen (C/N), but decreased the soil betaG/(NAG+LAP) ratio, suggesting that pig manure could benefit the degradation of soil cellulose and the accumulation of soil organic carbon. Applying NPK increased the activities of soil betaG, NAG, and LAP, but decreased the AP activity, with a decrement of 34% as compared with CK. Under the application of NPK, the soilbetaG/AP and (NAG+ LAP)/AP ratios increased, but the ratios of soil organic carbon to total phosphorus (C/P) and of soil total nitrogen to total phosphorus (N/P) decreased, indicating that chemical fertilizers could induce the accumulation of soil inorganic phosphorus, and inhibit the microbial functions of degrading polysaccharides and phosphate phospholipids.


Identification of AaAtg8 as a marker of autophagy and a functional autophagy-related protein in Aedes albopictus.
Aedes albopictus is a primary vector of hundreds of pathogens. Strong environmental adaptability and extensive global distribution of Aedes albopictus make it a severe threat to human health. Autophagy is a cellular process involved in maintenance of cellular homeostasis and recirculation of cytoplasm to generate macromolecule constituents and energy under different stress conditions. Many autophagy-related (Atg) proteins have been identified in yeast and were found in various organisms subsequently, indicating that the basic mechanism of autophagy is well conserved in eukaryotes. Among all Atg proteins, Atg8 plays important roles in autophagy and is widely used as a marker to monitor autophagic activity in yeast, Drosophila, nematodes, zebrafish and mammals. By now, Atg proteins in Aedes albopictus have not been reported yet and the autophagy pathway in Aedes albopictus remains unclear. This study identified a homolog of Atg8 from Aedes albopictus and named it AaAtg8. Sequence analysis revealed that AaAtg8 was highly conserved in the Atg8 family. This work proved that AaAtg8 was a functional Atg protein of Aedes albopictus and expressed during developmental and adult stages of Aedes albopictus. Moreover, the study also established the basic methods for autophagy study in C6/36 cells. First, it was proved that both rapamycin and starvation were applicable ways to induce autophagy in C6/36 cells, and that 3-methyladenine and chloroquine could be used to inhibit early and late stages of autophagy in C6/36 cells, respectively. Second, the results in this study showed that monodansylcadaverine staining could be used to detect autophagy in C6/36 cells. Additionally, the study revealed that the level of autophagy in C6/36 cells could be monitored by the turnover assay of AaAtg8 or fluorescent AaAtg8. Taken together, this study identified AaAtg8, the first reported Atg protein in Aedes albopictus. It also provided useful methods for studying autophagy in Aedes albopictus. To our knowledge, this is the first work about autophagy in Aedes albopictus.


Annexins Bridging the Gap: Novel Roles in Membrane Contact Site Formation.
Membrane contact sites (MCS) are specialized small areas of close apposition between two different organelles that have led researchers to reconsider the dogma of intercellular communication via vesicular trafficking. The latter is now being challenged by the discovery of lipid and ion transfer across MCS connecting adjacent organelles. These findings gave rise to a new concept that implicates cell compartments not to function as individual and isolated entities, but as a dynamic and regulated ensemble facilitating the trafficking of lipids, including cholesterol, and ions. Hence, MCS are now envisaged as metabolic platforms, crucial for cellular homeostasis. In this context, well-known as well as novel proteins were ascribed functions such as tethers, transporters, and scaffolds in MCS, or transient MCS companions with yet unknown functions. Intriguingly, we and others uncovered metabolic alterations in cell-based disease models that perturbed MCS size and numbers between coupled organelles such as endolysosomes, the endoplasmic reticulum, mitochondria, or lipid droplets. On the other hand, overexpression or deficiency of certain proteins in this narrow 10-30 nm membrane contact zone can enable MCS formation to either rescue compromised MCS function, or in certain disease settings trigger undesired metabolite transport. In this "Mini Review" we summarize recent findings regarding a subset of annexins and discuss their multiple roles to regulate MCS dynamics and functioning. Their contribution to novel pathways related to MCS biology will provide new insights relevant for a number of human diseases and offer opportunities to design innovative treatments in the future.


Detection of cryptosporidium in immunosuppressed patients.
Cryptosporidium is an important cause of diarrhoeal disease in children and immunosuppressed persons. It is an opportunistic pathogen. A study was done to determine the frequency of Cryptosporidium in immunosuppressed persons. Fecal samples were collected from Jinnah Postgraduate Medical Centre Karachi during July to December 2003 and they consisted of three categories of patients which included cancer patients (10) diabetics (20) and patients on dialysis (20). Direct microscopy in saline and iodine was done to detect parasites. Detection of Cryptosporidium from fecal samples was done by Kinyoun method. Bacteriological study was also done to determine any bacterial pathogens. Out of 50 fecal samples Cryptosporidium was found in 20 (40%) of cases. Among the different groups Cryptosporidium was found in 80% of cancer patients, 25% diabetics and 35% dialysis patients. Distribution of Cryptosporidium according to gender indicated more cases in males (87%) among cancer patients and 40% among dialyzed patients while diabetic patients showed similar distribution. Among the different age groups male patients were found to be between 40-49 years group for all categories of patients while more positive cases were detected in females in 30-39 years age group. Direct microscopy did not indicate any ova or parasite and bacteriological study indicated Salmonella and Shigella spp. in stool samples. This study provides indication of the possibility of Cryptosporodisis in immunosuppressed patient and further comprehensive study is required to clearly establish the relationship of opportunistic infections in immunosuppressed patients.


The dimensions of the hip labrum can be reliably measured using magnetic resonance and computed tomography which can be used to develop a standardized definition of the hypoplastic labrum.
The purpose of this study was to examine the existing literature to determine the dimensions of the acetabular labrum, with a focus on hypotrophic labra, including the modalities and accuracy of measurement, factors associated with smaller labra, and any impacts on surgical management. Four databases (PubMed, Ovid [MEDLINE], Cochrane Database, and EMBASE) were searched from database inception to January 2020. Two reviewers screened the literature independently and in duplicate. Methodological quality of included papers was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Where possible, data on labral size were combined using a random effects model. Twenty-one studies (5 level II, 9 level III, 7 level IV) were identified. This resulted in 6,159 patients (6,436 hips) with a mean age of 34.3 years (range 8.4-85). The patients were 67.3% female with an average follow-up of 57.3 months. There was no consistent definition of labral size quoted throughout the literature. The mean width on MRI/MRA was 7.3 mm (95% CI 6.9-7.8 mm), on computed tomography arthrography was 8.7 mm (95% CI 8.0-9.3), and during arthroscopy was 5.0 mm (95% CI 4.9-5.2). Inter-observer reliability was good to excellent in all modalities. Labral hypotrophy may be associated with increased acetabular coverage. Hypertrophic labra were highly associated with acetabular dysplasia (r = - 0.706, - 0.596, - 0.504, respectively; P < 0.001). Labral width can reliably be measured utilizing imaging techniques including magnetic resonance and computed tomography. The pooled mean labral width was 6.2 mm, and height 4.6 mm. The establishment of a gold-standard of measurement on arthroscopy and advanced imaging would aid in clinical decision-making regarding treatment options for patients presenting with a painful hip, particularly those with hypoplastic labra, and provide radiological guidelines for standardized labrum size classifications. Level IV.


Influence of Chitosan Ascorbate Chirality on the Gelation Kinetics and Properties of Silicon-Chitosan-Containing Glycerohydrogels.
The influence of the chirality of chitosan ascorbate on the gelation kinetics and the properties of hybrid silicon-chitosan-containing glycerohydrogels were studied with a deep estimation of the stereospecificity of chitosan polysalts with l- and d-ascorbic acid diastereomers and their biological effects. It has been established that l- and d-diastereomerically enriched chitosan ascorbates are characterized by a positive Cotton effect and differ in the wavelength of the maximum of the dichroic band (250 and 240 nm), as well as in the values of its specific ellipticity (21.8 × 10⁵ and 39.2 × 10⁵ deg·mL·dm-1·g-1), the sign of specific optical rotation (+ and -), the type of dispersion curves (anomalous and smooth), as well as the condensed phase morphology (anisodiametric particles with optical anisotropy and confocal domains of spherical shape, respectively). In the biomimetic sol-gel synthesis of silicon-chitosan-containing glycerohydrogels using silicon tetraglycerolate as a precursor, it was found that chitosan d-ascorbate retarded gelation. Thin congruent plates obtained from the corresponding glycerohydrogels based on chitosan d-ascorbate have higher mechanical strength and elasticity under uniaxial stretching and lower values of Young's modulus. It has been shown that the systems based on chitosan d-ascorbate show the greatest antibacterial activity against Staphylococcus aureus 209P and Escherichia coli 113-13 and significantly promote the viability of normal human dermal fibroblasts. The results of our assessment of the biological properties of chitosan polysalts are unexpected, since ascorbic acid exhibits biological activity as its l-isomer only.


Perspectives on testing for toxic agents.
A series of observations and comments are made with respect to several areas of toxicology: these are briefly discussed. Some innovative areas receive discussion as representing substantial progress made in the field of toxicology in recent years. Topics included raise a number of questions: what agents should we test, and how should we go about selecting them; what is the importance of allowing for genetic diversity in carrying out tests that are meaningful for humans; and what is the relevance of studies in pharmacokinetics in the laboratory to humans. Human studies, because of ethical considerations, must be indirect, through access to available autopsy and surgical human tissues. Also, drug trials and clinical studies must be exploited. Cancer testing and evaluation is briefly commented on. Systemic toxicity is considered in respect to possible improved ways of determining the "NOEL," that is, the no-observed-effect level. Suggestions for improving study of mixtures of chemicals are considered. The rapid advances in molecular biology have significantly strengthened our ability to trace the action of chemicals in the body from exposure to disease. It is very important that training in toxicology be based on a sound disciplinary training in one of the classic fields of the biomedical sciences, such as biochemistry, pharmacology, molecular biology. It is concluded that advances in the past decade have made the practice of toxicology a much more scientific endeavor, especially in its use of the latest developments in basic biomedical sciences.


LC-PDA-ESI-MSn analysis of phenolic and iridoid compounds from Globularia spp.
Plants produce a great number of metabolites with potentially useful biological activities. Species from the genus Globularia (Plantaginaceae) are known as sources of different phenolic and iridoid compounds. Globularia alypum L. is a medicinal plant used as a healing agent in many Mediterranean countries. Similarities in phytochemical composition are often observed for related species. For Globularia spp., such findings were mostly based on identification of several isolated compounds from distinct species. To our knowledge, this is the first study that enables simultaneous comparison of phytochemical profiles from several members of the genus Globularia. Liquid chromatography-photodiode array detection-electrospray ionization-tandem mass spectrometry was used for the analysis of methanolic extracts of aerial parts obtained from four Globularia species (G. alypum, G. punctata, G. cordifolia and G. meridionalis). In total, 85 compounds were identified or tentatively identified based on comparison of their retention time, UV and MSn (up to MS4 ) spectra to those of standard compounds and/or to literature data. Among these, high relative amounts of bioactive molecules such as globularin, globularifolin, asperuloside and verbascoside (acteoside) were found. Apart from providing new insights into the phytochemistry and chemotaxonomy of selected Globularia species, results of this study complement existing MS/MS spectral data and could enable easier mass spectrometric profiling of certain bioactive compounds such as iridoids and phenylethanoids in related plant species, genera and families. Copyright © 2016 John Wiley & Sons, Ltd.


Concomitant ipsilateral carotid endarterectomy and stenting is an effective treatment for tandem carotid artery lesions.
Data regarding the treatment of tandem carotid artery lesions at the bifurcation and ipsilateral, proximal common carotid artery (CCA) are limited. It has been suggested that concomitant treatment with carotid endarterectomy (CEA) and proximal ipsilateral carotid artery stenting confers a high risk of stroke and death. The objective of this study was to evaluate the technique and outcomes of this hybrid procedure at a single institution. A retrospective chart review was performed including patients who underwent CEA + ipsilateral carotid artery stenting for treatment of atherosclerotic carotid artery disease between December 2007 and April 2017. Primary endpoints were postoperative myocardial infarction, neurologic event, and perioperative mortality. Twenty-two patients (15 male [68%]) underwent CEA + ipsilateral carotid artery stenting with a mean follow-up of 67 ± 77 months. The mean age was 70.0 ± 6.1 years old, all with a prior smoking history (eight current smokers [64%]). Twelve patients (55%) were treated for symptomatic disease and three had a prior ipsilateral CEA (one also with CAS). Computed tomographic angiography imaging was performed preoperatively in 21 patients (95%). CEA was performed first in 18 patients (82%) followed by ipsilateral carotid artery stenting. CEA was performed with a patch in 20 and eversion endarterectomy in two patients. Ipsilateral CCA was stented in 21 patients (96%) and one innominate was stented in a patient with a right CEA. Additional endovascular interventions were performed in three patients: 1 innominate stent, 1 distal ipsilateral internal carotid artery stent, and 1 right subclavian artery stent. All proximal stents were placed with sheath access through the endarterectomy patch in 12 (55%), CCA in 7 (32%), and through the arteriotomy before patching in 3 (14%). Distal internal carotid artery clamping was performed in 18 (90%, available 20) of patients before ipsilateral carotid artery stenting. All proximal lesions were successfully treated endovascularly with no open conversion. One dissection was created and treated effectively with stenting. One perioperative stroke (4.5%) occurred in a patient treated for symptomatic disease, 1 postoperative myocardial infarction (4.5%), and 2 patients (9.1%) with cranial nerve injuries. There was one patient who expired within 30 days, shortly after discharge for unknown reasons. The mean length of stay was 2.6 ± 2.0 days. In appropriately selected patients, concomitant CEA and ipsilateral carotid artery stenting can be safely performed in high-risk patients with a low risk of myocardial infarction, neurologic events, and perioperative mortality when careful surgical technique is used, using direct carotid access, and distal carotid clamping for cerebral protection before stenting.


Influence of polyvascular disease on cardiovascular event rates. Insights from the REACH Registry.
Cardiovascular event rates have been shown to increase substantially with the number of symptomatic disease locations. We sought to assess the risk profile, management and subsequent event rates of polyvascular disease patients. Consecutive outpatients were assessed for atherosclerotic risk factors and medications in the REACH Registry. A total of 19,117 symptomatic patients in Europe completed a 2-year follow-up: 77.2% with single arterial bed disease (coronary artery or cerebrovascular or peripheral arterial disease) and 22.8% with polyvascular disease (>/= 1 disease location). Polyvascular disease patients were older (68.5 +/- 9.4 vs 66.3 +/- 9.9 years, p < 0.0001), more often current or former smokers (64.9% vs 58.7%, p < 0.0001), and more often suffered from hypertension (59.5% vs 46.6%, p < 0.0001) and diabetes (34.5% vs 25.9%, p < 0.0001) than single arterial bed disease patients. Despite more intense medical therapy, risk factors (smoking, hypertension, low fasting glucose, and low fasting total cholesterol) were less often controlled in polyvascular disease patients. This was associated with substantially more events over 2 years compared with single arterial bed disease patients (cMACCE [cardiovascular death/non-fatal stroke/non-fatal MI] odds ratio, 1.63 [95% CI, 1.45-1.83], p < 0.0001). In conclusion, polyvascular disease patients have more cardiovascular risk factors, and the prognosis for these patients is significantly worse than for patients with single arterial bed disease. This suggests a need to improve detection and consequent medical treatment of polyvascular disease.


Modified Facial Translocation Approach in a One-Month Old With a Skullbase Tumor.
The authors present a patient of a neonate with a skull base extragonadal germ cell tumor requiring a modified facial translocation approach for resection. A 1-week-old female presented with right proptosis, eyelid edema, and nasal obstruction. Imaging revealed a 3-cm right-sided skull base mass involving the right maxillary, ethmoid, sphenoid sinuses, orbit, infratemporal fossa, and cavernous sinus via skull base erosion. The lesion was refractory to chemotherapy and required surgical excision. A modified facial translocation approach with preservation of anterior maxillary bone vascularization was used to remove the tumor, which was found to be teratoma with yolk-sac features. The patient tolerated surgery well and was noted to have minimally affected facial skeleton growth at 2-year follow-up. This modified facial translocation approach allowed safe access to this anterior skull base tumor with acceptable morbidity and mild facial growth effects so far.


Effect of lactic acid isomers on keratinocyte ceramide synthesis, stratum corneum lipid levels and stratum corneum barrier function.
Alpha-hydroxy acids are effective agents for the treatment of skin xerosis and it is known that, following treatment with lotions containing D,L-lactic acid, the stratum corneum prevents xerosis more effectively. To date, the relative efficacy of the different isomers of lactic acid has not been evaluated and the mode of action of lactic acid in improving stratum corneum resilience is not known. The objective of the present studies was to determine the effects of lactic acid isomers on keratinocyte ceramide biosynthesis, stratum corneum barrier function and the resistance of the stratum corneum to the appearance of skin xerosis. In vitro, lactic acid enhanced the production of ceramides by keratinocytes. L-Lactic acid was more effective than the D isomer (300% increase vs 100% increase). Carbon label from lactic acid was incorporated into all keratinocyte lipid species and a greater incorporation of label into ceramides was achieved with L-lactate than with D-lactate. In vivo, lactic acid increased the levels of stratum corneum ceramides. Whereas, lotions containing L-lactic acid resulted in the greatest increase (48% increase) followed by D,L-lactic acid (25% increase), D-lactic acid had no effect on stratum corneum ceramide levels. The increases in stratum corneum ceramide levels following lactic acid treatment also led to improvements in stratum corneum barrier function, measured by transepidermal water loss following a challenge to the skin with SLS and in the regression phase of a moisturization efficacy study. Significant improvements in barrier function and resistance to the appearance of skin xerosis were observed following L-lactic acid and D,L-lactic acid, but not following D-lactic acid treatment. From these results we believe that lactic acid, particularly the L isomer, stimulates ceramide biosynthesis leading to increased stratum corneum ceramide levels which results in superior lipid barrier and a more effective resistance against xerosis.


High Resolution of Plasmonic Resonance Scattering Imaging with Deep Learning.
The dark-field microscopy (DFM) imaging technology has the advantage of a high signal-to-noise ratio, and it is often used for real-time monitoring of plasmonic resonance scattering and biological imaging at the single-nanoparticle level. Due to the limitation of the optical diffraction limit, it is still a challenging task to accurately distinguish two or more nanoparticles whose distance is less than the diffraction limit. Here, we propose a computational strategy based on a deep learning framework (NanoNet), which will realize the effective segmentation of the scattered light spots in diffraction-limited DFM images and obtain high-resolution plasmonic light scattering imaging. A small data set of DFM and the corresponding scanning electron microscopy (SEM) image pairs are used to learn for obtaining a highly resolved semantic imaging model using NanoNet, and thus highly resolved DFM images matching the resolution of those acquired using SEM can be obtained. Our method has the ability to transform diffraction-limited DFM images to highly resolved ones without adding a complex optical system. As a proof of concept, a highly resolved DFM image of living cells through the NanoNet technique is successfully made, opening up a new avenue for high-resolution optical nanoscopic imaging.


Prognostic significance of acute renal injury in acute tumor lysis syndrome.
Acute tumor lysis syndrome (ATLS) caused by the destruction of malignant cells leads to metabolic abnormalities, which may either remain isolated (biological ATLS) or subsequently lead to renal dysfunction (clinical ATLS). We compared hospital and 6-month survival in patients with ATLS with hematological malignancies with or without acute renal injury. Sixty-three patients (median age, 50 years; range, 32-64) were included with ATLS. Twenty-eight had no ARI (including 17 (61%) who subsequently required dialysis) whereas 35 had an ATLS-related ARI (including 31 (89%) who required dialysis). Acute leukemia (n = 28) and lymphoma (n = 30) were the main malignancies. All patients had high tumor burdens. Hospital and 6-month mortality rates were significantly lower in patients without ARI (7% and 21%, respectively) than in the ATLS-related renal injury group (51% and 66%). After adjustment for acute disease severity, presence of ARI at ICU admission was associated with higher hospital mortality (odds ratio, 10.41; 95% confidence interval, 2.01-19.170; p = 0.005) and 6-month mortality (odds ratio, 5.61; 95% confidence interval, 1.64-54.66; p = 0.006), compared to patients without renal injury. Our study suggests that in patients with ATLS, ICU management when acute renal injury is present is associated with higher short- and long-term mortality.


Rectal carcinoma treated by preoperative irradiation: MR imaging and histopathologic correlation.
We evaluated the role of MR imaging in assessing the effect of preoperative irradiation in 11 patients with primary rectal carcinoma. Findings on MR images obtained before radiotherapy and 5-6 weeks afterward were analyzed and correlated with the histopathological findings (nine patients) or the findings at laparotomy (two patients). Before irradiation, the tumor volumes on MR images were between 3.3 and 51.7 cm3 (mean 19.7 cm3). After irradiation, the volumes were from 0.8 to 33.2 cm3 (mean, 10.4 cm3), representing a decrease in volume of 11% to 88% (mean, 55%). On the MR images obtained before irradiation, the tumors were confined to the bowel wall in four cases (stage A-B1), penetrated the perirectal fat in six cases (stage B2), and involved an adjacent organ in one case (stage B3). After irradiation, no apparent changes were seen in the MR appearance of the local tumor stage in nine of the 11 patients. In one patient, progression of stage was suspected on the postirradiation MR images, but this was not confirmed at histologic examination. In one patient, possible downstaging occurred after irradiation, although this could not be proved. Our findings suggest that MR imaging may be useful for determining the effect of preoperative radiotherapy on rectal carcinomas.


Factor IX and deep vein thrombosis.
Elevated levels of several coagulation factors have been found to be associated with an increased risk of thrombosis. In this perspective article, Dr. Lowe examines the implications of the report by Bezemer and coworkers in this issue for our understanding of the mechanisms involved and how they should direct future research.


Viral gastroenteritis: the USS THEODORE ROOSEVELT experience.
Although the spread of disease on board Navy ships is not a novel concept, the medical department of the USS THEODORE ROOSEVELT recently experienced a significant outbreak of viral gastroenteritis while at sea. The impact on the crew and medical department is reviewed in this case report. The use of the Navy Disease Non-Battle Injury tracking system was validated. Furthermore, we proposed the placement of waterless, isopropyl alcohol-based, hand-cleaning systems in strategic locations throughout the ship, to help prevent and minimize the spread of future disease. Finally, more stringent recommendations regarding sick in quarters status and careful utilization of consumable resources are necessary components of an effective outbreak management strategy.


[Legionnaires' disease--risk factors and symptoms].
The analysis of published data concerning demographic and medical risk factors and clinical manifestation and outcome observed in Legionella pneumonia were presented in this study. The aim of this study was to discuss the problem of high diversity of symptoms of legionnaires' disease as well as risk factors frequency presented in patients with legionellosis. The different risk factors and clinical picture of Legionella pneumonia were presented, depending on kind of infection (sporadic/epidemic), populations and place of infection (travel-associated, nosocomial, community-acquired). The high percentage of patients with legionellosis and with digestive symptoms (15-70%) was pointed. The presence of digestive symptoms like: diarrhea, vomiting, nausea might cause problem in diagnosis because of suggestion of another etiological agent. Moreover, the hypothesis of M.Sabria et al. regarding the correlation between the exposure and kind and clinical manifestation of Legionella pneumonia was discussed.


Fractionation of brain macromolecules. Chromatography on hydroxyapatite of soluble proteins and nucleic acids from whole rat brain and the effect of autolysis.
1. A procedure for the chromatographic fractionation of soluble brain proteins on calcium hydroxyapatite is described. Chromatograms obtained are reproducible; approximately 11 protein and at least three nucleic acid components can be identified. The effects of column dimensions and flow rate on the chromatograms obtained are described. 2. One of the nucleic acid components appears to correspond to soluble RNA and another to ribosomal RNA. Treatment of homogenates by procedures that cause the removal of ribosomes from soluble extracts also cause the disappearance of the component corresponding to ribosomal RNA. Centrifugation of rat-brain homogenates prepared in 0.25m-sucrose at 105400g for 90min. causes the sedimentation of ribosomes as well as the disappearance of the component corresponding to ribosomal RNA. Extraction of brain tissue, or particulate fractions prepared from brain, with dilute buffers causes the solubilization of part of the ribosomal RNA that then can subsequently be identified in the chromatogram. 3. Autolysis under aerobic conditions has been shown to cause an increase in the nucleic acid component in the chromatogram that corresponds to the ribosomal RNA. Aerobic autolysis causes part of the ribosomal RNA to be solubilized, as evidenced by its failure to be sedimented by centrifugation at 105400g for 90min. and by its appearance in the fraction corresponding to ribosomal RNA in the chromatogram. These changes were not observed when autolysis was carried out under anaerobic conditions. Aerobic autolysis also caused changes in those proteins that are strongly adsorbed on the gel. 4. In general, the proteins of the cell sap appeared to be fairly stable to autolysis. Marked differences in the chromatograms are observed when soluble proteins from the particle fraction were autolysed and chromatographed.


Sequential cranial ultrasound and cerebellar diffusion weighted imaging contribute to the early prognosis of neurodevelopmental outcome in preterm infants.
To evaluate the contribution of sequential cranial ultrasound (cUS) and term-equivalent age magnetic resonance imaging (TEA-MRI) including diffusion weighted imaging (DWI) to the early prognosis of neurodevelopmental outcome in a cohort of very preterm infants (gestational age [GA] <31 weeks). In total, 93 preterm infants (median [range] GA in weeks: 28.3 [25.0-30.9]) were enrolled in this prospective cohort study and underwent early and term cUS as well as TEA-MRI including DWI. Early cUS abnormalities were classified as normal, mild, moderate or severe. Term cUS was evaluated for ex-vacuo ventriculomegaly (VM) and enlargement of the extracerebral cerebrospinal fluid (eCSF) space. Abnormalities on T1- and T2-weighted TEA-MRI were scored according to Kidokoro et al. Using DWI at TEA, apparent diffusion coefficients (ADCs) were measured in four white matter regions bilaterally and both cerebellar hemispheres. Neurodevelopmental outcome was assessed at two years' corrected age (CA) using the Bayley Scales of Infant and Toddler Development, third edition. Linear regression analysis was conducted to explore the correlation between the different neuroimaging modalities and outcome. Moderate/severe abnormalities on early cUS, ex-vacuo VM and enlargement of the eCSF space on term cUS and increased cerebellar ADC values on term DWI were independently associated with worse motor outcome (p<.05). Ex-vacuo VM on term cUS was also related to worse cognitive performance at two years' CA (p<.01). These data support the clinical value of sequential cUS and recommend repeating cUS at TEA. In particular, assessment of moderate/severe early cUS abnormalities and ex-vacuo VM on term cUS provides important prognostic information. Cerebellar ADC values may further aid in the prognostication of gross motor function.


Reanalysis of the Mayo Lung Project data: the impact of confounding and effect modification.
To examine whether age at entry, history of cigarette smoking, exposure to non-tobacco lung carcinogens, or previous pulmonary illnesses were confounders or effect modifiers of the relation between screening and lung cancer mortality in the Mayo Lung Project. The Mayo Lung Project was a randomised, controlled, clinical trial conducted between 1971 and 1986 in 9211 male smokers over the age of 45 in Minnesota (USA). The group screened received chest x ray examination and sputum cytology every four months for six years. The unscreened group were recommended to obtain usual care (annual chest x ray examination and sputum cytology). After follow up, lung cancer mortality was similar in both groups. Proportional hazard models were used to analyse data. A variable was considered a confounder if its inclusion in a model changed the rate ratio for screening by more than 15%; a variable was considered an effect modifier if its stratum-specific rate ratio for screening differed by a factor of two. None of the four aforementioned variables changed the rate ratio associated with screening (1.07) by more than 2%. The effect of screening may have differed by years smoked (rate ratio for smoking fewer than 30 years 2.4; rate ratio for smoking 30 or more years 1.0), though we suspect that this result occurred by chance. Adjustment for or stratification by four established lung cancer risk factors did not alter the original findings of the Mayo Lung Project.


Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Obesity.
Obesity and its related comorbidities can negatively influence the outcomes of certain infectious diseases. Specific dosing recommendations are often lacking in the product label for patients with obesity that leads to unclear guidance in practice. Higher rates of therapeutic failure have been reported with some fixed dose antibiotics and pragmatic approaches to dose modification are limited for orally administered agents. For i.v. antimicrobials dosed on weight, alternate body size descriptors (ABSDs) have been used to reduce the risk of overdosing. These ABSDs are mathematical transformations of height and weight that represent fat-free weight and follow the same principles as body surface area (BSA)-based dosing of cancer chemotherapy. However, ABSDs are rarely studied in pivotal phase III studies and so can risk the underdosing of antimicrobials in patients with obesity when incorrectly applied in the real-world setting. Specific case examples are presented to highlight these risks. Although general principles may be considered by clinicians, a universal approach to dose modification in obesity is unlikely. Studies that can better distinguish human body phenotypes may help reduce our reliance on height and weight to define dosing. Simple and complex technologies exist to quantify individual body composition that could improve upon our current approach. Early evidence suggests that body composition parameters repurposed from medical imaging data may improve upon height and weight as covariates of drug clearance and distribution. Clinical trials that can integrate human body phenotyping may help us identify new approaches to optimal dose selection of antimicrobials in patients with obesity.


Camera calibration by multiplexed phase encoding of coordinate information.
A simple camera calibration method based on the principle of phase encoding and coordinate transformation is proposed. We use a reference coordinate frame encoded as a phase distribution by multiplexing the x and y directions. From this, we suggest a phase demodulation system. The coordinate transformation induced by the imaging is exploited to estimate the intrinsic and extrinsic camera parameters by using the least-squares method. Thus, a robust and noniterative estimation scheme is obtained. Simulations and experimental results show the feasibility of the proposal. Because of the potential for calibrating projectors, the proposed method could be used to calibrate fringe-projection systems.


Beta2-microglobulin is a better predictor of treatment-free survival in patients with chronic lymphocytic leukaemia if adjusted according to glomerular filtration rate.
Even in the era of newer and sophisticated prognostic markers, beta(2)-microglobulin (B2M) remains a simple but very powerful predictor of treatment-free survival (TFS) and overall survival (OS) in patients with chronic lymphocytic leukaemia (CLL). However, B2M levels are heavily influenced by the patient's glomerular filtration rate (GFR) and this study aimed to evaluate whether GFR-adjusted B2M (GFR-B2M) had improved prognostic value compared to unadjusted B2M in a cohort of over 450 consecutive CLL patients from two separate institutions. Multivariate analysis identified a significantly shorter TFS in patients who were ZAP-70 + (P < 0.001), with increased GFR-B2M (P < 0.001), and del(11q) or del(17p) as detected by fluorescence in situ hybridization (FISH; P < 0.001). When OS was evaluated by multivariate analysis, age 65 years or older (P < 0.001) and poor risk FISH abnormalities (P < 0.001) had a confirmed adverse prognostic impact, but the predictive value of GFR-B2M was lost in the validation analysis. In all survival models, B2M did not attain independent significance unless GFR-B2M was eliminated from the analysis. In conclusion, GFR-B2M is a better predictor of TFS than unadjusted B2M in CLL patients.


Control parameters for fabrication of single-electron transistors using field-emission-induced electromigration.
We report a simple method for the control of electrical characteristics of planar-type metal-based single-electron transistors (SETs) using field-emission-induced electromigration. The advantages of this method are as follows: (1) the fabrication of SETs is achieved by only passing a field emission current through a nanogap and (2) the charging energy of SETs can be controlled by adjusting the magnitude of the applied current during the procedure. In order to better control the electrical properties of the SETs, we investigate the relation between control parameters of the method and electrical characteristics of the SETs. When the field-emission-induced electromigration with the preset current of 500 nA was applied to the nanogaps, current-voltage characteristics of the nanogaps displayed the suppression of electrical current at low-bias voltages known as Coulomb blockade at 16 K. In addition, Coulomb blockade voltage was clearly modulated by the gate voltage periodically at 16 K, resulting in the formation of single island in the SETs by the field-emission-induced electromigration. Furthermore, as the preset current was increased, the charging energy of the SETs was decreased with decreasing the initial gap separation of the nanogaps. These results imply that the electrical characteristics of the SETs are controllable by the preset current of the method and the initial gap separation of the nanogaps. Field-emission-induced electromigration procedure allows us to simply control electrical characteristics of planar-type metal-based SETs.


Organizational-Professional Conflict in the Collegiate and Secondary School Practice Settings: A Sequential, Mixed-Methods Study.
Athletic trainers (ATs) are employed in various settings, which may use 1 of 3 organizational infrastructure models: (1) the sport/athletic model, (2) the medical model, and (3) the academic model. These different settings and organizational infrastructure models may result in varying levels of organizational-professional conflict (OPC). However, how OPC may differ across infrastructure models and practice settings is not known. To examine the prevalence of OPC among ATs in various organizational infrastructures and explore ATs' perceptions of OPC, including its precipitating and mitigating factors. Sequential explanatory mixed-methods study with equal emphasis on quantitative and qualitative components. Collegiate and secondary school institutions. Five hundred ninety-four ATs from collegiate and secondary schools. We conducted a national cross-sectional survey using a validated scale to assess OPC. We then followed the quantitative survey with individual interviews. Trustworthiness was established with multiple-analyst triangulation and peer debriefing. Athletic trainers experienced low to moderate degrees of OPC with no differences across practice settings or infrastructure models. Poor communication, others' unfamiliarity with the AT's scope of practice, and lack of medical knowledge were precipitating factors for OPC. Organizational relationships founded on trust and respect for one another; administrative support in that ATs were listened to, decisions were endorsed, and appropriate resources provided; and autonomy given to the AT were key components to preventing OPC. Most ATs experienced primarily low to moderate OPC. However, OPC continues to permeate professional practice to some extent in collegiate and secondary school settings, regardless of the infrastructure model used. The findings of this study highlight the role of administrative support that allows for autonomous AT practice as well as effective communication that is direct, open, and professional to decrease OPC.