In vitro upregulation of erythrocytes glucose uptake by Rhaphnus sativa extract in diabetic patients.
In diabetes, both the increase in the oxidative stress and the decrease in the antioxidant defense may elevate the susceptibility of diabetic patients to many pathological complications. So, the aim of the present study was to investigate the effect of superoxide dismutase (SOD) like activity protein, partially purified from radish (Rhaphnus sativa) on uptake of glucose in vitro by erythrocytes of diabetic patients. In hyperglycemic patients, erythrocytes malondialdehyde level was highly significantly increased (P < 0.0001) than that of the control. However, the erythrocytes glutathione content and glutathione reductase activity, were both highly significantly decreased (P < 0.0001) compared to that corresponding control values. The glucose uptake by erythrocytes of diabetic patients was highly significantly decreased (P < 0.0001) with increasing hyperglycemia, while it was highly significantly elevated (p < 0.0001) after addition of the partially purified SOD like activity protein. On the other hand, the malondialdehyde concentration was highly significantly reduced (p < 0.001) on adding the partially purified protein. It thus can be concluded that, an appropriate support for enhancing antioxidant supply, such as SOD like activity protein from natural sources, may help control blood glucose level and may prevent clinical complications of diabetes.


Uses of calcium hydroxide: an online study guide.
The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section presents uses of calcium hydroxide related to apexogenesis, apexification, direct pulp cap, indirect pulp cap, internal resorption that has perforated laterally, intracanal medication, control of periapical exudates, aid in canal debridement, apical control to control obturation, external inflammatory root resorption, repair of perforations, treatment of horizontal root fractures, root canal sealers, and vertical root fractures.


Construction and nucleotide sequence of a cDNA encoding the full-length preprotein for human branched chain acyltransferase.
A cDNA (1.6 kilobases) for branched chain acyltransferase (E2b) isolated from a human liver library encoded only the amino-terminal half of the protein (Hummel, K. B., Litwer, S., Bradford, A. P., Aitken, A., Danner, D. J., and Yeaman, S. J. (1988) J. Biol. Chem. 263, 6165-6168). Here we report the isolation of other cDNAs which encode the carboxyl-terminal half of E2b and the construction of a cDNA which encodes the entire pre-E2b. cDNA from the original clone encoding the leader sequence, lipoate binding domain, and E3 binding domain was ligated to the cDNA from a clone which by restriction maps contained an additional 3' sequence. Both cDNAs used in the construct made a fusion protein in their original phage isolate recognized by antibodies to E2b. The nucleotide sequence of the constructed cDNA was determined, and the 1431 base pairs in the open reading frame encoded a protein of 477 amino acids. In vitro transcription and translation of this cDNA produced a 57-kDa protein recognized by E2b-specific antibodies. Mouse liver mitochondria imported and processed the 57-kDa protein to a 52-kDa antigenic protein which co-migrated with E2b isolated from tissue. Comparing the protein structure of this human pre-E2b protein with that for other acyltransferase proteins showed a similarity in structure throughout all the proteins suggesting evolutionary conservation. Branched chain acyltransferase from Pseudomonas putida showed the most similarity to human E2b.


Self-organization of orientation maps in a formal neuron model using a cluster learning rule.
Self-organization of orientation maps due to external stimuli in the primary visual area of the cerebral cortex is studied in a two-layered neural network which consists of formal neuron models with a sigmoidal output function. A cluster learning rule is proposed as an extended Hebbian learning rule, where a modification of synaptic connections is influenced by an activation of neighboring output neurons. By making use of self-consistent Monte Carlo method, we evaluate output responses of neurons against explicit inputs after the learning. An orientation map calculated from the output responses reproduces characteristic features of biological ones. Moreover quantitative analysis of our results are consistent with those of experimental results. It is shown that the cluster learning rule plays an important role in forming smooth changes of preferred orientations.


Mobile educational tool based on augmented reality technology for tooth carving: results of a prospective cohort study.
Augmented reality (AR) technology has been shown to be effective in displaying information and presenting three-dimensional objects. Although AR applications are commonly used by learners via mobile devices, plastic models or two-dimensional images are still commonly used in tooth carving practice. Learners practicing tooth carving face a challenge due to the three-dimensional features of teeth as there is a lack of tools available that provide sequential guidance. In this study, we developed an AR-based tooth carving practice tool (AR-TCPT) and compared it to a plastic model to evaluate its potential as a practice tool as well as its user experience. To model tooth carving, we created a three-dimensional object from sequential steps that included the maxillary canines and maxillary first premolars (16 steps), mandibular first premolars (13 steps), and mandibular first molars (14 steps). Image markers, created using Photoshop software, were assigned to each tooth. An AR-based mobile application was developed using the Unity engine. For tooth carving, 52 participants were randomly assigned to a control group (n = 26; using a plastic tooth model) or an experimental group (n = 26; using the AR-TCPT). User experience was evaluated using a 22-item questionnaire. Data were comparatively analyzed using the nonparametric Mann-Whitney U test via the SPSS program. The AR-TCPT detects image markers with the mobile device camera and displays three-dimensional objects for tooth fragmentation. Users can manipulate the device to view each step or examine the shape of a tooth. The results of the user experience survey revealed that the AR-TCPT experimental group scored significantly higher in tooth carving experience compared with the control group that used the plastic model. Compared with the conventional plastic model, the AR-TCPT provided a better user experience for tooth carving. The tool is highly accessible as it is designed to be used on mobile devices by users. Further studies are required to determine the educational impact of the AR-TCTP on quantitative scoring of carved teeth as well as individual user's carving abilities.


Isolated Medial Rectus Palsy in a Patient After Percutaneous Transluminal Coronary Angioplasty.
Diplopia, a very common ophthalmic complaint, is a potential first sign of severe pathology. Here, we present a case of an atypical midbrain infarction targeting the lateral subnucleus of the oculomotor nuclear complex that manifested as diplopia with no additional symptoms of a stroke episode. Axial diffusion-weighted and coronal T2-weighted magnetic resonance imaging showed an infarct in the rostral midbrain affecting the subnucleus of the medial rectus located ventrally. Diffusion-weighted imaging was used to diagnose the medial rectus nucleus infarct.


Immunohistochemical studies of human renal cell carcinomas for ABO(H) blood group antigens, T antigen-like substance and carcinoembryonic antigen.
Immunohistochemical methods were used to examine human renal cell carcinoma tissues for the presence of ABO(H) blood group antigens, T antigen-like substance and carcinoembryonic antigen. None of the 30 tumors examined showed positive staining for the blood group antigens. In the normal adjacent kidney tissues blood group antigens were noted in the glomeruli, distal tubules and collecting ducts, while proximal convoluted tubules were uniformly negative. The presence of T antigen-like substance was noted in 10 of the 30 tumors (33 per cent). Likewise, T antigen-like substance appeared at the distal tubules and collecting ducts in the normal adjacent kidney tissues, while proximal convoluted tubules were negative. With a monoclonal antibody to carcinoembryonic antigen, 19 of the 30 tumors (63 per cent) showed positive staining. Carcinoembryonic antigen also was observed in the glomeruli and tubular epithelia in the normal kidney tissues. Immunohistochemical findings of T antigen-like substance and carcinoembryonic antigen were not found to be correlated with the tumor grade, cell type and stage, as well as survival of patients with renal cell carcinoma.


Nicotine and gastric cancer.
About 60 components in cigarette smoke are considered to be carcinogens, namely polycyclic aromatic hydrocarbons, nitrosamines, aromatic amine, trace metals, as well as nicotine. Nicotine is considered to be one of the active components in cigarette smoke, and its association with tumorigenesis is enigmatic. Nonsteroidal antiinflammatory drugs are widely accepted as antitumor agents to treat patients with cancer by inhibiting cyclooxygenase-2 activity. Stimulation of tumor growth by nicotine involves different processes of cell proliferation and angiogenesis. Study results, with the use of animal xenograft models and cell culture systems, show that nicotine stimulates the progression of tumor growth, through a cyclooxygenase-2-dependent pathway. On the basis of these findings, nicotine seems to be a potent mitogenic agent in modulating tumor cell proliferation, and selective cyclooxygenase-2 inhibitors are promising antitumor agents for gastric cancer in smokers.


The ultrastructure of rabbit sclera after scleral crosslinking with riboflavin and blue light of different intensities.
We aimed to determine the ultrastructural changes of collagen fibrils and cells in the rabbit sclera after scleral crosslinking using riboflavin and blue light of different intensities. Scleral crosslinking is known to increase scleral stiffness and may inhibit the axial elongation of progressive myopic eyes. The equatorial parts of the sclera of one eye of six adult albino rabbits were treated with topical riboflavin solution (0.5 %) followed by irradiation with blue light (200, 400, 650 mW/cm(2)) for 20 min. After 3 weeks, the ultrastructure of scleral cells and the abundance of small- (10-100 nm) and large-diameter (>100 nm) collagen fibrils in fibril bundles of different scleral layers were examined with electron microscopy. In the scleral stroma of control eyes, the thickness of collagen fibrils showed a bimodal distribution. The abundance of small-diameter collagen fibrils decreased from the inner towards the outer sclera, while the amount of large-diameter fibrils and the scleral collagen content did not differ between different stroma layers. Treatment with riboflavin and blue light at 200 mW/cm(2) did not induce ultrastructural changes of cells and collagen fibrils in the scleral stroma. Treatment with blue light of higher intensities induced scleral cell activation in a scleral layer-dependent manner. In addition, outer scleral layers contained phagocytes that engulfed collagen fibrils and erythrocytes. Blue light of the highest intensity induced a reduction of the scleral collagen content, a decreased abundance of large-diameter collagen fibrils, and an increased amount of small-diameter fibrils in the whole scleral stroma. The data indicate that in rabbits, scleral crosslinking with riboflavin and blue light of 200 mW/cm(2) for 20 min is relatively safe and does not induce ultrastructural alterations of scleral cells and of the collagen composition of the scleral stroma. Irradiation with blue light of intensities between 200 and 400 mW/cm(2) induces scleral cell activation, which may contribute to scleral scarring and stiffening. Higher intensities cause scleritis.


Quantification of regional differences in aortic stiffness in the aging human.
There has been a growing awareness over the past decade that stiffening of the aorta, and its attendant effects on hemodynamics, is both an indicator and initiator of diverse cardiovascular, neurovascular, and renovascular diseases. Although different clinical metrics of arterial stiffness have been proposed and found useful in particular situations, there remains a need to understand better the complex interactions between evolving aortic stiffness and the hemodynamics. Computational fluid-solid-interaction (FSI) models are amongst the most promising means to understand such interactions for one can parametrically examine effects of regional variations in material properties and arterial geometry on local and systemic blood pressure and flow. Such models will not only increase our understanding, they will also serve as important steps towards the development of fluid-solid-growth (FSG) models that can further examine interactions between the evolving wall mechanics and hemodynamics that lead to arterial adaptations or disease progression over long periods. In this paper, we present a consistent quantification and comparison of regional nonlinear biaxial mechanical properties of the human aorta based on 19 data sets available in the literature and we calculate associated values of linearized stiffness over the cardiac cycle that are useful for initial large-scale FSI and FSG simulations. It is shown, however, that there is considerable variability amongst the available data and consequently that there is a pressing need for more standardized biaxial testing of the human aorta to collect data as a function of both location and age, particularly for young healthy individuals who serve as essential controls.


Survival after pancreatectomy with major arterial resection and reconstruction.
Absence of major arterial tumor involvement has generally been regarded as a major criterion for resectability of pancreatic tumors. We hypothesize that resection of a tumor-involved hepatic artery (HA) or celiac artery (CA) with reconstruction may offer a survival benefit to patients whose tumors were traditionally regarded as unresectable. All patients with pancreatic adenocarcinoma treated between 1996 and 2007 were reviewed. Patients were included if they underwent resection of the HA or CA during pancreatectomy. Survival was analyzed by Kaplan-Meier survivor functions, Cox proportional hazard models, and the log rank test. Twelve patients (six men and six women) with adenocarcinoma underwent pancreatectomy with resection of a tumor-involved HA (n = 2) and/or CA (n = 10). Median age at diagnosis was 62 years (range, 53-73 years). All patients completed neoadjuvant chemoradiotherapy with or without full dose chemotherapy before resection. Procedures performed were six extended pancreaticoduodenectomies, two proximal subtotal pancreatectomies, two distal pancreatectomies, and two total pancreatectomies. Ten cases involved celiac resections, and two had isolated HA resections. The 60-day mortality was 17% (2 of 12). Median survival after diagnosis was 20 months (range, 6-41 months). Median survival after resection was 17 months (range, 1-36 months). Survival was not statistically significantly related to age, sex, margin status, or preoperative CA19-9 level. The 3-year survival was 17%. There were no 5-year survivors. Resection of the HA or CA with reconstruction may prolong survival for selected patients who undergo pancreatic resection after neoadjuvant therapy. However, this aggressive approach did not result in any long-term survivors in our series.


A lightweight deep learning architecture for the automatic detection of pneumonia using chest X-ray images.
Pneumonia is a life-threatening respiratory lung disease. Children are more prone to be affected by the disease and accurate manual detection is not easy. Generally, chest radiographs are used for the manual detection of pneumonia and expert radiologists are required for the assessment of the X-ray images. An automatic system would be beneficial for the diagnosis of pneumonia based on chest radiographs as manual detection is time-consuming and tedious. Therefore, a method is proposed in this paper for the fast and automatic detection of pneumonia. A deep learning-based architecture 'MobileNet' is proposed for the automatic detection of pneumonia based on the chest X-ray images. A benchmark dataset of 5856 chest X-ray images was taken for the training, testing, and evaluation of the proposed deep learning network. The proposed model was trained within 3 Hrs. and achieved a training accuracy of 97.34%, a validation accuracy of 87.5%, and a testing accuracy of 94.23% for automatic detection of pneumonia. However, the combined accuracy was achieved as 97.09% with 0.96 specificity, 0.97 precision, 0.98 recall, and 0.97 F-Score. The proposed method was found faster and computationally lesser expensive as compared to other methods in the literature and achieved a promising accuracy.


Abortive initiation by RNA polymerase II in vitro at the adenovirus 2 major late promoter.
We have investigated the formation of the first phosphodiester bond by RNA polymerase II in vitro. The template was a cloned DNA bearing the adenovirus 2 major late promoter; transcription factors and RNA polymerase II were provided by a HeLa cell nuclear extract. Dinucleotide primers and single nucleoside triphosphates were used as substrates. We found that accurate initiation does occur when only one phosphodiester bond can be formed; however, all of the resulting dinucleotide-primed trimers are abortively initiated. Synthesis of the trimers by RNA polymerase II requires ATP or dATP and is sensitive to low concentrations of alpha-amanitin. Treatments which abolish the ability of the preinitiation complex to synthesize long RNAs also eliminate the ability to abortively initiate. Abortive initiation proceeds for at least one-half h at 25 degrees C, at which point up to 4 mol of transcript/mol of template have been synthesized. The level of abortive initiation (per template molecule) is not significantly reduced by 0.025% Sarkosyl or by 10-fold dilution of the reaction, consistent with the initiation complex remaining intact during abortive initiation.


Current Resources for Evidence-Based Practice, January 2021.
An extensive review of new resources to support the provision of evidence-based care for women and infants. The current column includes a discussion of the WHO's new Labour Care Guide and commentaries on reviews focused on prevention of mastitis in women during the postpartum period and a comparison of outcomes for fresh versus frozen embryos for in vitro fertilization.


Multi-activity tetracoordinated pallado-oxadiazole thiones as anti-inflammatory, anti-Alzheimer, and anti-microbial agents: Structure, stability and bioactivity comparison with pallado-hydrazides.
Herein, we report a comparative study based on structure, thermal and solution stability, and biopotency against lipoxygenase (LOX), butyrylcholinesterase (BChE) and microbes for Pd(II) compounds of N,O,S bearing 5-(C5H4XR)-1,3,4-oxadiazole-2-thiones (L') of type [PdL'Cl2] (P'n) and N,O bearing respective hydrazides (L) of type trans-[PdL2Cl2] (Pn) {X = C, R = 4-I, 2-Br, 4-NO2, 3-NO2, 2-Cl, 3-Cl (n = 1-6, serially); X = N (n = 7)}. Spectral techniques (IR, EI-MS, NMR) and physicochemical evaluations successfully characterized the new compounds. The L' behaved as bidentate S-N donors bonded through exocyclic sulfur and N-3' nitrogen, while L acted as amino N donors. UV-vis (solution speciation) and thermal degradation profiles consistently confirmed the greater stability for P'n than Pn compounds. These compounds manifested varying degree in vitro potential to inhibit LOX, BChE and several bacteria and fungi, affected mainly by Pd(II) presence, M-L binding mode, nature and position of R, or halo groups electronegativity. Molecular docking with human 5-LOX and BChE further validated the respective experimental inhibition findings and explored several putative mechanistic interactions (H-bonding, π-stacking, π-alkyl, π-S, etc.) at the enzyme active sites. Pn generally offered superior antimicrobial and anti-LOX (anti-inflammatory) potential than respective P'n compounds, with P3/P'5, P(2,3,7)/P'3, and P6 being comparable, better and equivalent to ampicillin, nystatin and baicalein, the reference antibacterial, antifungal and anti-LOX drugs, respectively. Contrarily, the anti-BChE activity of P'n was found better than Pn compounds, showing P'2/P1 as the most promising anti-Alzheimer drug candidates. This study bares important structural and mechanistic aspects in optimizing antimicrobial, anti-inflammatory and anti-Alzheimer activities, highlighting some potential future pallado-drug candidates.


KIH-802: 2-nitroimidazole-1-acetohydroxamate as a hypoxic cell radiosensitizer.
We have identified potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802) as a hypoxic cell radiosensitizer potentially superior to Miso. The water-soluble acetohydroxamates of 2-nitroimidazole (KIH-802; free acid 801) and 4-nitroimidazole (KIH-852) were designed, synthesized, and evaluated by in vitro and in vivo screening against EMT6 cells. Enhancement ratios of KIH-802 and 801 were 1.92 and 1.68, respectively, compared with 1.58 for MISO all at 1 mM. These acetohydroxamates are also expected to be more effective in vitro than SR-2508 based on our previous experiments. In vivo ERs of KIH-802, 801, and 852 were 1.75, 1.50, and 1.35, respectively, compared with 1.57 for MISO all at the same dose of 200 mg/kg. The data clearly show that the addition of an acetohydroxamic acid moiety to the 2-nitroimidazole skeleton can enhance radiosensitizing ability.


The optimal timing of antihypertensive medication administration for morning hypertension in patients with cerebral infarction.
Morning hypertension is an independent risk factor for cardiovascular diseases, particularly stroke. However, the optimal time at which to take antihypertensive medication to treat morning hypertension remains unclear. We prospectively enrolled elderly patients (over 65 years old) with morning hypertension who had suffered an ischemic stroke (or strokes). Additional treatments (one of six arms) were randomly administered for 10 weeks in the morning, in the evening or at bedtime (n=15 for each time point/medication). The patients measured their blood pressure and heart rate at home for 14 days prior to the intervention and for the final 14 days, and recorded the data in a blood pressure diary. The patients' urinary albumin/creatinine ratios were evaluated before and after the 10-week intervention. A total of 270 patients were enrolled in this study (mean age: 75.6±5.8 years; female/male ratio: 125/145). Their morning and evening systolic blood pressures were significantly decreased after following any of the study medication dosing schedules (P<0.001). However, the reductions in the differences between the morning and evening systolic blood pressures were significant only when the medication was taken in the evening or at bedtime (P<0.001 with repeated measures analysis of variance). Furthermore, the recovery rate from morning hypertension was also higher when the medication was taken in the evening (40.0%) or at bedtime (45.6%), rather than in the morning (22.2%; P=0.003 with the χ(2)-test). Antihypertensive medication taken in the evening or at bedtime is the most effective in treating morning hypertension when the patient adheres to the medication regimen.


The life-cycle proteins RodA of Escherichia coli and SpoVE of Bacillus subtilis have very similar primary structures.
Comparison of the predicted amino acid sequence of the cell-cycle RodA protein with the National Research Foundation protein sequence database shows that the 370-amino-acid RodA, a protein that is essential for wall elongation in Escherichia coli and maintenance of the rod shape of the cell, is highly analogous, in terms of primary structure, with the Bacillus subtilis SpoVE protein involved in stage V of sporulation.


The function of migratory epidermis in the healing of tympanic membrane perforations in guinea-pig. A photographic study.
During observations on healing traumatic perforations in guinea-pig tympanic membranes, a specific appearance was seen on the surface of the epidermis as it closed the perforations. In this experiment, this pattern was identified on 15 tympanic membranes in 10 guinea pigs, and serial photography was used to record the healing process in 6 perforations over 5 days. This study shows that epidermis accumulates at the inferior margin of the perforation (the side from which it migrates) and then closes over the defect. Epidermal migration appears to be a key factor in this healing process.


Effect of extracellular ATP on the growth of hormone-refractory prostate cancer in vivo.
To investigate whether the antineoplastic action of ATP on hormone-refractory prostate carcinoma (HRPC) cells in vitro also occurs in vivo, by examining the effect of ATP in vivo on tumours resulting from implanted HRPC cells in mice. HRPC tumour cells DU145 and PC-3 were implanted into male nude athymic mice. The effect of daily intraperitoneal (i.p.) injections of ATP (25 mm) on the growth of freshly implanted and established HRPC tumours was assessed. Histological examination using light and electron microscopy was used to confirm retention of the original ultrastructure of the implanted tumours. Daily i.p. injections of ATP significantly reduced the growth of freshly implanted DU145 tumour by 57.8% (P = 0.003), and reduced the rate of growth of established DU145 tumour by 69.0% (P = 0.006). ATP also significantly reduced the growth of freshly implanted PC-3 tumour by 68.9% (P < 0.001). ATP treatment had no adverse effects on the host mice. Our results show, for the first time, that ATP effectively reduces the growth of advanced HRPC tumours in vivo. This may represent a step in establishing ATP as an effective agent for HRPC treatment.


Antiplatelet agents for the secondary prevention of ischaemic stroke in patients with or without renal dysfunction.
Studies on using antiplatelet agents for secondary prevention in ischaemic stroke patients with renal dysfunction are limited. The Taiwan Stroke Registry database was used to compare the efficacy of antiplatelet agents. From the Taiwan Stroke Registry data, 39 174 acute ischaemic stroke patients were identified and were classified into three groups by antiplatelet agent: aspirin, clopidogrel and dual antiplatelet therapy (DAPT) with a combination of aspirin and clopidogrel. The re-stroke incidence and 1-year mortality were stratified by estimated glomerular filtration rate (eGFR) levels at admission: ≥90, 60-89 and <60 ml/min/1.73 m2 or on dialysis. Compared to the aspirin group, the re-stroke differences were not statistically significant for the clopidogrel group [adjusted subhazard ratio 0.95, 95% confidence interval (CI) 0.84-1.08] and the DAPT group (adjusted subhazard ratio 1.03, 95% CI 0.77-1.39) after controlling for the competing risk of death. The mortality rate increased as the eGFR level declined. In addition, compared to patients taking aspirin, there was no statistically significant difference in overall 1-year mortality for the clopidogrel group (adjusted hazard ratio 1.11, 95% CI 0.95-1.29) and for the DAPT group (adjusted hazard ratio 1.01, 95% CI 0.67-1.54). The results were consistent in different subgroups stratified by eGFR levels. There was no difference in the risks of recurrent stroke and 1-year mortality amongst ischaemic stroke patients with or without renal dysfunction receiving antiplatelet agents with aspirin, clopidogrel or dual agents with a combination of aspirin and clopidogrel, regardless of their renal dysfunction status.


Detergent-resistant membranes in human erythrocytes and their connection to the membrane-skeleton.
In cell membranes, local inhomogeneity in the lateral distribution of lipids and proteins is thought to exist in vivo in the form of lipid 'rafts', microdomains enriched in cholesterol and sphingolipids, and in specific classes of proteins, that appear to play specialized roles for signal transduction, cell-cell recognition, parasite or virus infection, and vesicular trafficking. These structures are operationally defined as membranes resistant to solubilization by nonionic detergents at 4 degree C (detergent-resistant membranes, DRMs). This definition appears to be necessary and sufficient, although additional manoeuvres, not always described with sufficient detail, may be needed to ensure isolation of DRMs, like mechanical homogenization, and changes in the pH and/or ionic strength of the solubilization medium. We show here for the human erythrocyte that the different conditions adopted may lead to the isolation of qualitatively and quantitatively different DRM fractions, thus contributing to the complexity of the notion itself of lipid raft. A significant portion of erythrocyte DRMs enriched in reported lipid raft markers, such as flotillin-1, flotillin-2 and GM1, is anchored to the spectrin membrane-skeleton via electrostatic interactions that can be disrupted by the simultaneous increase in pH and ionic strength of the solubilization medium.


Perceived end-of-life educational needs by clinical trials nurses at a comprehensive cancer center.
Determine palliative care end-of-life (EOL) educational needs among clinical trials nurses (CTNs) at an urban comprehensive cancer center. The End-Of-Life Professional Caregiver Survey (EPCS) was used to determine the EOL educational needs of CTNs and collect demographics on years of experience, education, past EOL-specific training, and possession of their own advanced directive. The "Surprise Question" was also asked to explore the percent of patients on clinical trials who may be nearing EOL. Twenty-nine CTNs completed the survey. Mean years of experience as an RN and CTN was 10.45 and 2.5, respectively. 79% and 17% held a bachelors or master's degree, respectively. Twenty-seven percent reported previous End-of-Life Nursing Education Consortium (ELNEC) or similar training and 20% stated they had their own advanced directive. Mean total score for the EPCS was 94.83, with subscale means of 42.41 for the Patient and Family Centered Communication (PFCC), 26.9 for Cultural and Ethical Values (CEV), and 25.52 for the Effective Care Delivery (ECD). Highest scoring items included confidence in communicating with colleagues about EOL care, being present with dying patients, and recognizing patients who are appropriate for hospice referral. Lowest scoring items included participating in code status discussions, resolving ethical issues and family conflicts at EOL, and addressing requests for assisted suicide. Responses to the Surprise Question indicated that 27.5% of the CTNs would not be surprised if half or more of their patients died within the next 12 months. Many patients with cancer on clinical trials may be nearing EOL. CTNs perceive the need for education to increase confidence in handling difficult communication.


An ergonomic appraisal of the use and functional efficiency of condom urinals in the male patient with spinal cord paralysis.
The variety and method of use of condom urinals was reviewed and an investigation conducted to ascertain the problems which arise. Effects arising from material failure and methods of use were disclosed.


Analysis of the dehydration process of caffeine using backscattering and transmission Raman spectroscopy.
In the present study, the dehydration process of caffeine hydrate (CAH) was investigated by calibrating the moisture content in the caffeine tablet using backscattering Raman spectroscopy (BRS) and transmission Raman spectroscopy (TRS). The detectable depth of BRS is limited by its shallow laser penetration, while TRS is a powerful tool to determine the content of active pharmaceutical ingredients in a tablet. Our results suggest that the accuracy of a TRS-based calibration model falls beyond that of a BRS-based model. Based on the calibration used, the model was built by calculating the differences in the crystalline structures between hydrate and anhydrous caffeine. Moreover, it was demonstrated that the dehydration process occurred by switching water molecules between hydration sites of caffeine.


Determinants of COVID-19 pandemic in India: an exploratory study of Indian states and districts.
The countries across the globe are facing one of the worst infectious diseases in modern times in the form of COVID-19 pandemic. Different measures have been taken to control and manage the outbreak of COVID-19 in these countries. There are two propositions in context of effective control and management of a pandemic like COVID-19. First, a strong and effective public health care system is essential for managing the public health crisis and the uneven responses to COVID-19 are mainly because of inadequate health infrastructure. Second, the spread of COVID-19 depends on the interplay of other social determinants at local level, and therefore, addressing the gaps in social determinants of COVID-19 at local level is critical to control and manage this pandemic. The present paper attempts to examine these two propositions in Indian context at states and districts level, respectively. Using the cross-sectional data and constructing composite indices of COVID-19 intensity and level of health infrastructure at state level, the results show that there is no robust relationship between level of health infrastructure and management of COVID-19 at state level as the states with better health infrastructure are also struggling to combat against COVID-19. The district-level analysis indicates a significant relationship between concentration of COVID-19 and social determinants as majority of the districts with higher concentration of COVID-19 are those which have social determinants below national average.


Author Correction: Impact of Enoxaparin +α Lipoic acid combination on oxidative stress, follicle development and apoptotic damage in ovarian ischemia reperfusion model.
Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (18): 6583-6592-DOI: 10.26355/eurrev_202209_29758-PMID: 36196708, published online on 30 September, 2022. After publication, the authors applied a correction to the Funding statement: "This Project was supported by the Scientific Research Projects Coordination Unit at Hatay Mustafa Kemal University. Project Number: 18. M. 088." There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/29758.


Effects of some inhibitors on the growth and lipid accumulation of oleaginous yeast Rhodosporidium toruloides and preparation of biodiesel by enzymatic transesterification of the lipid.
Microbial lipid produced using yeast fermentation with inexpensive carbon sources such as lignocellulosic hydrolyzate can be an alternative feedstock for biodiesel production. Several inhibitors that can be generated during acid hydrolysis of lignocellulose were added solely or together into the culture medium to study their individual inhibitory actions and their synergistic effects on the growth and lipid accumulation of oleaginous yeast Rhodosporidium toruloides. When the inhibitors were present in isolation in the medium, to obtain a high cell biomass accumulation, the concentrations of formic acid, acetic acid, furfural and vanillin should be lower than 2, 5, 0.5 and 1.5 g/L, respectively. However, the synergistic effects of these compounds could dramatically decrease the minimum critical inhibitory concentrations leading to significant growth and lipid production inhibitions. Unlike the above-cited inhibitors, sodium lignosulphonate had no negative influence on biomass accumulation when its concentration was in the range of 0.5-2.0 g/L; in effect, it was found to facilitate cell growth and sugar-to-lipid conversion. The fatty acid compositional profile of the yeast lipid was in the compositional range of various plant oils and animal tallow. Finally, the crude yeast lipid from bagasse hydrolyzate could be well converted into fatty acid methyl ester (FAME, biodiesel) by enzymatic transesterification in a tert-butanol system with biodiesel yield of 67.2% and lipid-to-biodiesel conversion of 88.4%.


Local Delivery of Nimustine Hydrochloride against Brain Tumors: Basic Characterization Study.
Convection-enhanced delivery (CED) delivers agents directly into tumors and the surrounding parenchyma. Although a promising concept, clinical applications are often hampered by insufficient treatment efficacy. Toward developing an effective CED-based strategy for delivering drugs with proven clinical efficacy, we performed a basic characterization study to explore the locally delivered characteristics of the water soluble nitrosourea nimustine hydrochloride (ACNU). First, ACNU distribution after CED in rodent brain was studied using mass spectrometry imaging. Clearance of 14C-labeled ACNU after CED in striatum was also studied. ACNU was robustly distributed in rodent brain similar to the distribution of the hydrophilic dye Evans blue after CED, and locally delivered ACNU was observed for over 24 h at the delivery site. Subsequently, to investigate the potential of ACNU to induce an immunostimulative microenvironment, Fas and transforming growth factor-β1 (TGF-β1) was assessed in vitro. We found that ACNU significantly inhibited TGF-β1 secretion and reduced Fas expression. Further, after CED of ACNU in 9L-derived intracranial tumors, the infiltration of CD4/CD8 lymphocytes in tumors was evaluated by immunofluorescence.CED of ACNU in xenografted intracranial tumors induced tumor infiltration of CD4/CD8 lymphocytes. ACNU has a robust distribution in rodent brain by CED, and delayed clearance of the drug was observed at the local infusion site. Further, local delivery of ACNU affects the tumor microenvironment and induces immune cell migration in tumor. These characteristics make ACNU a promising agent for CED.


Nuclear localization signal-enhanced RNA interference of EZH2 and Oct4 in the eradication of head and neck squamous cell carcinoma-derived cancer stem cells.
Metastasis is the major cause of high mortality in head and neck squamous cell carcinoma (HNSCC), in which HNSCC-derived cancer stem cells (CSCs) may be involved. Several reports have coupled non-viral gene delivery with RNA interference (RNAi) to target specific genes in cancer cells. However, the delivery efficiency of RNAi is limited and remained to be improved. Moreover, the therapeutic effect of non-viral gene delivery approaches on HNSCC-derived CSCs is still uncertain. In this study, we found that EZH2 and Oct4 are upregulated in HNSCC-derived ALDH1+/CD44+ CSC-like cells. Polyurethane-short branch PEI (PU-PEI)-based administration of double-stranded DNA (dsDNA) encoding small interfering RNA (siRNA) against EZH2 and Oct4 (siEZH2/siOct4) led to partial anti-cancer capacity and mild suppression of CSC-like properties. By pre-conjugation of nuclear localization signal (NLS) to siRNA-expressing dsDNA, the anti-cancer efficacy was enhanced due to elevated nuclear delivery. Notably, the NLS-preconjugated siEZH2/siOct4 constructs remarkably repressed epithelial-mesenchymal transdifferentiation (EMT) and radioresistance in ALDH1+/CD44+ CSC-like cells, in which Wnt5A and CyclinD1 may be involved respectively. We furthermore demonstrated that this improved method was capable of reducing tumor growth and metastasis in vivo. Our findings may provide a feasible non-viral gene delivery method to eradicate HNSCC-derived CSCs and improve HNSCC therapy.


n-alkanes as a substratum for riboflavin production. I. Investigations of the dynamics of the flavinogenesis in chosen yeasts of the genus candida.
For the first time the flavinogenic abilities of Candida flareri on a simple, fully defined medium with hydrocarbons were demonstrated. C flareri and C. guilliermondi on a synthetic medium with biotin and n-alkanes (n-decane and hexadecane) overproduce riboflavin with a considerable but varying efficiency. Among the two hydrocarbons examined n-hexadecane proved to be a more favourable source of carbon for the biosynthesis of this vitamin than n-decane. The quantities of riboflavin accumulated by C. flareri in an aerated culture are twice higher than those for C. guilliermondii (50.5 microgram/ml on hexadecane) in analogous conditions.


Cardiovascular effects of the aqueous extract of Gynostemma pentaphyllum Makino.
In the present study, the cardiovascular activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in the anaestetized guinea-pigs and has been compared with two of its isolated gypenosides (III, VIII) and with verapamil, a well-known Ca-antagonistic drug. The results obtained showed that the intravenous administration of the decoction of G. pentaphyllum (2.5, 5 and 10mg/kg) produced a protective effect against pitressin-induced coronaryspasm, arrhythmias and pressor response. Extract also increased the dose of ouabain required to cause ventricular tachyarrhythmias and lethality. Further extract reversed ouabain-induced persistent ventricular tachycardia and restored sinus rhythm in a dose-dependent manner. The results obtained have also shown that gypenosides III and VIII caused similar protective effects in both experimental models used; however, the duration of the action is lower than that of the extract containing corresponding quantities of gypenosides III and VIII.


Cholinergic effect on rat proximal convoluted tubule.
The effect of cholinergic agents on proximal tubular absorption of bicarbonate and fluid were examined to investigate the possible role of the cholinergic receptor in the regulation of renal function. Proximal convoluted tubule (PCT) and peritubular capillaries were perfused with bicarbonate-Ringer's solution containing radioactive inulin. Bicarbonate (total CO2) was determined by microcalorimetry. The rates of bicarbonate absorption (JHCO3) and fluid absorption (Jv) were 143.3 +/- 7.2 pEq/min.mm and 2.52 +/- 0.23 nl/min.mm, respectively. Addition of carbachol (10(-8) M) to the capillary perfusate reduced JHCO3 by 17% and Jv by 32%. A higher dose of carbachol (10(-6) M) did not further inhibit JHCO3 or Jv. Simultaneous perfusion of atropine (10(-5) M) together with carbachol (10(-8) M) abolished the inhibitory effect of carbachol on PCT transport. Atropine itself, however, had no effect on PCT transport. The inhibitory effect of carbachol was also diminished by lanthanum chloride (10(-4) M). Carbachol (10(-6) M) had no effects from the luminal side. W-7, a calmodulin antagonist, inhibited carbachol-induced effects. Ionophore A-23187 also inhibited Jv and JHCO3. However, there was no additive effect when A-23187 and carbachol were combined in the capillary perfusate. These results suggest that there are functional cholinergic receptors on the basolateral side of the PCT that can regulate JHCO3 and Jv. Calcium influx may play a role in mediating the cholinergic effects on PCT transport.


Pathological studies on atrioventricular conduction disturbances.
A histopathological study was made on 150 autopsied hearts according to the method of Lev in order to investigate the correlation of conduction disturbances with the branching pattern of the bundle branches. Subsequently, the study of bundle branch block and A-V block cases revealed that no explicit correlation existed between histopathological changes and functional disturbances nor between disturbances in conduction (i.e. breakdown of the physiological mechanism) and histopathological findings.


Natural Products: A Potential New Hope to Defeat Post-acute Sequelae of COVID-19.
The COVID-19 pandemic was the most significant public healthcare crisis worldwide. It was estimated that 80% of infected patients with COVID-19 have not fully recovered and developed one or more long-term symptoms, referred to as post-acute sequelae of COVID-19 (PASC). Seeking a treatment strategy for PASC has become a concerning topic since the sequelae can cause irreversible multiple organ damage and can severely compromise quality of life. It is indicated that PASC may be closely related to lung injury-induced hypoxia, excessive immune response, cytokine storm, gut bacteria imbalance, and endothelial dysfunction. Also, more and more research has indicated that angiotensin-converting enzyme 2 (ACE2) receptor, transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1), and nuclear factor erythroid 2-related factor 2 (Nrf2) can be considered as the targets to treat PASC. There is currently still no proven medication for PASC due to its complexity. Many clinical practices and studies have shown that natural products have great potential in preventing and treating PASC. Therefore, we intended to provide a comprehensive review of the current literature on PASC and the role of natural ingredients in PASC management. Meanwhile, this review provided meaningful insight for further study of natural ingredients to improve PASC and its clinical application.


Expression patterns of the DAZ-associated protein DAZAP1 in rat and human ovaries.
To evaluate the expression of DAZAP1 (deleted in azoospermia-associated protein 1) in rat and human ovaries. Experimental study. University hospital. Twelve corpus luteum (CL) specimens were collected during operation, either by laparoscopic surgery for CL rupture or by laparotomy for benign gynecologic conditions. Surgical excision of 12 human CL. Proteins analyzed by immunohistochemical staining, Western blotting, and co-immunoprecipitation experiments. DAZAP1 is expressed in rat and human luteal cells. Expression of DAZAP1 decreases with advancing stages of CL. Co-immunoprecipitation experiments show in vivo interaction of DAZ-like (DAZL) protein with DAZAP1 in the ovarian tissues. The expression patterns of DAZAP1 and DAZL are identical within rat and human ovaries. In mammalian species, DAZAP1 may be involved in diverse reproductive functions, ranging from cell cycle regulation and maturation of oocytes to differentiation of luteal cells.


Mitochondrial Damage-Associated Molecular Patterns (MTDs) Are Released during Hepatic Ischemia Reperfusion and Induce Inflammatory Responses.
Ischemia / reperfusion injury (IRI) during the course of liver transplantation enhances the immunogenicity of allografts and thus impacts overall graft outcome. This sterile inflammatory insult is known to activate innate immunity and propagate organ damage through the recognition of damage-associate molecular pattern (DAMP) molecules. The purpose of the present study was to investigate the role of mitochondrial DAMPs (MTDs) in the pathogenesis of hepatic IRI. Using in vitro models we observed that levels of MTDs were significantly higher in both transplantation-associated and warm IR, and that co-culture of MTDs with human and rat hepatocytes significantly increased cell death. MTDs were also released in an in vivo rat model of hepatic IRI and associated with increased secretion of inflammatory cytokines (TNF-α, IL-6, and IL-10) and increased liver injury compared to the sham group. Our results suggest that hepatic IR results in a significant increase of MTDs both in vitro and in vivo suggesting that MTDs may serve as a novel marker in hepatic IRI. Co-culture of MTDs with hepatocytes showed a decrease in cell viability in a concentration dependent manner, which indicates that MTDs is a toxic mediator participating in the pathogenesis of liver IR injury.


Methylmalonic acid and vitamin B12 in patients with heart failure.
Vitamin B12 deficiency among patients with heart failure (HF) may have been underestimated. High serum levels of methylmalonic acid (MMA) have been identified in several studies as an early indicator of vitamin B12 deficiency. Furthermore, MMA seems to constitute a biomarker of oxidative stress and mitochondrial dysfunction. There are scarce data regarding vitamin B12 and MMA in patients with HF. The aim of this study was to investigate vitamin B12 and MMA serum levels in patients with HF. One hundred five consecutive patients admitted to our hospital with symptoms and signs of acute decompensated HF were included in the study. Demographic and clinical characteristics as well as comorbidities and medical treatment before hospital admission were recorded. Transthoracic echocardiography was performed in all patients. Blood samples were collected during the first 24 hours of hospitalization and measured for complete blood count, biochemical profile, vitamin B12, N-terminal prohormone of brain natriuretic peptide, and MMA levels. Finally, 51 healthy individuals constituted the control group. A total of 43.8% of patients with HF had elevated MMA levels, but only 10.5% had overt vitamin B12 deficiency, defined as serum cobalamin levels below 189 pg/ml. Mean MMA level was higher in patients with HF than in controls (33.0 ± 9.6 vs. 19.3 ± 6.3 ng/ml; p < 0.001). This difference remained significant when adjusted for age, sex, vitamin B12, and folate serum levels and kidney function (B = 14.7 (9.6-19.7); p < 0.001). MMA levels were higher in patients with acutely decompensated chronic HF than in those with newly diagnosed acute HF (34.7 ± 10.5 vs. 30.7 ± 7.8 ng/ml; p = 0.036). Correlation analysis revealed significantly negative correlation between MMA and vitamin B12 levels only in patients without comorbidities. Patients with HF have elevated MMA levels, independent of age, gender, HF category, or comorbidities, possibly indicating subclinical vitamin B12 deficiency. Further research is needed to investigate subclinical vitamin B12 deficiency in patients with HF and/or to clarify whether MMA constitutes a biomarker of oxidative stress.


Supra-molecular hydrogen-bonding patterns in a 1:1 co-crystal of the N(7)-H tautomeric form of N6-benzoyl-adenine with 4-hy-droxy-benzoic acid.
The asymmetric unit of the title co-crystal, C12H9N5O·C7H6O3, contains one mol-ecule of N6-benzoyl-adenine (BA) and one mol-ecule of 4-hy-droxy-benzoic acid (HBA). The N6-benzoyl-adenine (BA) has an N(7)-H tautomeric form with nonprotonated N-1 and N-3 atoms. This tautomeric form is stabilized by a typical intra-molecular N-H⋯O hydrogen bond between the carbonyl (C=O) group and the N(7)-H hydrogen on the Hoogsteen face of the purine ring, forming a graph-set S(7) ring motif. The primary robust R22(8) ring motif is formed in the Watson-Crick face via N-H⋯O and O-H⋯N hydrogen bonds (involving N1, N6-H and the carboxyl group of HBA). Weak inter-actions, such as, C-H⋯π and π-π are also observed in this crystal structure.


Coxsackievirus B3 infection induces changes in the expression of numerous piRNAs.
Piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis and are widely distributed among somatic tissues. However, little is known about piRNAs in HeLa cells infected with coxsackievirus B3 (CVB3). In this study, we systematically investigated changes in piRNA expression in HeLa cells infected with CVB3 using high-throughput sequencing technology. piRNA expression profiles in CVB3-infected HeLa cells were examined at 3, 6 and 9 h postinfection (pi). Of the 32,826 piRNAs that were annotated in the NCBI database, 151,571, 89,698 and 76,626 piRNAs were detected in CVB3-infected HeLa cells at 3, 6 and 9 h pi, respectively. Compared with normal cells, 211, 72 and 94 piRNAs were differentially expressed in CVB3-infected HeLa cells at 3, 6 and 9 h pi, respectively. Thirteen piRNAs, including four novel piRNAs, exhibited concurrent changes in CVB3-infected HeLa cells. The changes in the expression of these 13 piRNAs was confirmed in CVB3-infected HeLa cells and 293T cells by stem-loop RT-qPCR at 3, 6 and 9 h pi. The target genes of 13 piRNAs were predicted. The four novel piRNAs were associated with LTR/ERV, LINE/L1 and LTR/ERVK repetitive elements located on different chromosomes. These findings may promote a better understanding of the regulatory mechanism of pathophysiological changes induced by CVB3 infection.


High-performance liquid chromatographic analysis of a novel carbapenem antibiotic in human plasma and urine.
High-performance liquid chromatographic methods for quantification of a novel carbapenem anti-infective agent, I, in plasma and urine have been developed, validated, and applied to clinical samples. The carbapenem is stabilized in the matrix by the addition of a non-nucleophilic buffer, rapid freezing, and storage at -70 degrees C. After addition of another carbapenem, II, as internal standard, plasma proteins are precipitated with acetonitrile, which is subsequently extracted from the sample with methylene chloride. A portion of the aqueous phase is injected onto a reversed-phase phenyl column that is eluted with 4% (v/v) acetonitrile in 15 mM ammonium phosphate (pH 7.4). The urine assay entails addition of the internal standard II to buffered urine, which is subsequently extracted with methylene chloride prior to injection of the aqueous phase onto a cation-exchange column. The urine assay mobile phase is 5% v/v tetrahydrofuran in 100 mM sodium acetate (pH 5.4). The detector response at 313 nm is a linear (r greater than 0.99) function of concentration over the ranges 0.50-100 micrograms/ml and 2.0-200 micrograms/ml for the plasma and urine assays, respectively. Thermal degradation products do not interfere with either assay. These assays have proven to be accurate, precise, reproducible, and rugged during clinical sample analyses.


Extravasation of Brownian Spheroidal Nanoparticles through Vascular Pores.
In modern cancer treatment, there is significant interest in studying the use of drug molecules either directly injected into the bloodstream or delivered by nanoparticle (NP) carriers of various shapes and sizes. During treatment, these carriers may extravasate through pores in the tumor vasculature that form during angiogenesis. We provide an analytical, computational, and experimental examination of the extravasation of point particles (e.g., drug molecules) and finite-sized spheroidal particles. We study the advection-diffusion process in a model microvasculature, consisting of a shear flow over and a pressure-driven suction flow into a circular pore in a flat surface. For point particles, we provide an analytical formula [Formula: see text] for the dimensionless Sherwood number S, i.e., the extravasation rate, in terms of the pore entry resistance (Damköhler number κ), the shear rate (Péclet number P), and the suction flow rate (suction strength Q). Brownian dynamics (BD) simulations verify this result, and our simulations are then extended to include finite-sized NPs, in which no analytical solutions are available. BD simulations indicate that particles of different geometries have drastically different extravasation rates in different flow conditions. In general, extreme aspect ratio particles provide a greater flux through the pore because of favorable alignment with streamlines entering the pore and less hindered interaction with the pore. We validate the BD simulations by measuring the in vitro transport of both bacteriophage MS2 (a spherical NP) and free dye (a model drug molecule) across a porous membrane. Despite their vastly different sizes, BD predicts S = 8.53 E-4 and S = 27.6 E-4, and our experiments agree favorably, with Sexp=10.6 E-4± 1.75 E-4 and Sexp=16.3 E-4 ± 3.09 E-4, for MS2 and free dye, respectively, thus demonstrating the practical utility of our simulation framework.


A variant of the split notochord syndrome.
Split notochord syndrome has been described in several previous case reports; however, we recently treated a patient with a previously undescribed variant of this syndrome. A 2.5-g baby girl was admitted to the neonatal intensive care unit with a skin-covered mass on the back, and a portion of intestine, with meconium being passed, attached to it. The legs were equino varus, and the anus was anteriorly displaced. Radiographs were consistent with a lumbar split notochord, and the patient was taken to the operating room for closure. During surgery, the skin-covered mass was opened and found to contain loops of small intestine leading to an intussuscepted cecum and an open ended duplication of the cecum attached to the end of the spinal cord. The small intestinal loops exited the abdomen from a peritoneal-lined opening to the back. The loops were returned to the abdomen after releasing the duplication from the cord. The peritoneal connection was closed with a purse string suture, and the abdomen was opened. The duplication of the cecum was partially amputated and the rest was used to create a chimney-type stoma. The intraabdominal exploration was significant for nonrotation as well as a normal rectum. The postoperative course was uneventful. This case is unique because most cases of split notochord only involve a fistula to the rectum. In this case, a major part of the small bowel had herniated. Moreover, there was an open duplication similar to that found in extrophy. In approaching such a situation, it is also important to have the neurosurgeon available to provide adequate closure of the back similar to a myelomeningocele.


Association of Physician Characteristics With Early Adoption of Virtual Health Care.
The rapid transition to virtual health care has depended on physician and patient abilities to adopt new technology and workflows. Physicians transitioning more slowly or not at all could result in access challenges for their patients. To identify physician characteristics associated with the transition to virtual health care in a large regional health care system. This retrospective cross-sectional study uses administrative health system databases to analyze data from all 3473 physicians providing ambulatory care through a large New England health care system, which includes 12 hospitals and their ambulatory practices, from October 1, 2019, through December 31, 2020. Physicians characterized based on gender, popularized generational demographic cohort (Silent Generation, born 1928-1945; Baby Boomers, born 1946-1964; Generation X, born 1965-1980; and Millennials, born 1981-1996), specialty (behavioral health, primary care, medical, and surgical), and hospital affiliation as well as selected patient characteristics (number of visits and proportion of patients with self-pay or Medicaid insurance, aged 65 years or older, preference for speaking a language other than English, from a racial or ethnic minority group, and with an active patient portal). Early adoption of virtual health care. Bivariate comparisons were made, and regression modeling was used to examine characteristics associated with the likelihood of early adoption of virtual health care. Of 3473 physicians conducting ambulatory visits during the study period, 1624 (46.8%) were women, 83 (2.4%) were in the Silent Generation, 994 (28.6%) were Baby Boomers, 1637 (47.1%) were in Generation X, and 759 (21.9%) were Millennials. There were 1649 physicians (47.5%) in medical specialties, 749 physicians (21.6%) in surgical specialties, and 248 physicians (7.1%) in behavioral health. After accounting for other characteristics, female (odds ratio [OR], 1.23; 95% CI, 1.06-1.44), behavioral health (OR, 2.92; 95% CI, 2.11-4.04), and primary care (OR, 1.69; 95% CI, 1.36-2.09) physicians had greater odds of being early adopters, and physicians in the Silent Generation (OR, 0.39, 95% CI, 0.24-0.65) and in surgical specialties (OR, 0.46; 95% CI, 0.38-0.57) were less likely to be early adopters. Patient characteristics were less strongly associated with physician adoption. In this cross-sectional study, there was physician-level variation in the adoption of virtual health care, with female, primary care, and behavioral health physicians in this system most likely to lead the transformation to virtual health care.


Congruence of evidence for a Methanopyrus-proximal root of life based on transfer RNA and aminoacyl-tRNA synthetase genes.
Among 60 organisms, the intraspecies genetic distances between tRNAs cognate for different amino acids, between the initiator and elongator tRNAs for Met, and between potentially paralogous pairs of aminoacyl-tRNA synthetases are found to be at a minimum within the Methanopyrus kandleri genome. These results indicate an exact congruence between the evidence from tRNA and aminoacyl-tRNA synthetase genes locating the root of life closest to this organism.


Gene expression profiles in the testis associated with testis-ova in adult Japanese medaka (Oryziaslatipes) exposed to 17α-ethinylestradiol.
The occurrence of oocytes in the testis (testis-ova) of several fish species is often associated with exposure of estrogenic chemicals. However, induction mechanisms of the testis-ova remain to be elucidated. To develop marker genes for detecting testis-ova in the testis, adult male medaka were exposed to nominal concentration of 100 ng L(-1) of 17α-ethinylestradiol (EE2) for 3-5 weeks, and 800 ng estradiol benzoate (EB) for 3 weeks (experiment I), and a measured concentration of 20 ng L(-1) EE2 for 1-6 weeks (experiment II). Histological analysis was performed for the testis, and microarray analyses were performed for the testis, liver and brain. Microarray analysis in the estrogen-exposed medaka liver showed vitellogenin and choriogenin as estrogen responsive genes. Testis-ova were induced in the testis after 4 weeks of exposure to 100 ng L(-1) EE2, 3 weeks of exposure to 800 ng EB, and 6 weeks of exposure to 20 ng L(-1) EE2. Microarray analysis of estrogen-exposed testes revealed up-regulation of genes related to zona pellucida (ZP) and the oocytes marker gene, 42Sp50. Using quantitative RT-PCR we confirmed that Zpc5 gene can be used as a marker for the detection of testis-ova in male medaka.


Syntaxin-5's flexibility in SNARE pairing supports Golgi functions.
Deficiency in the conserved oligomeric Golgi (COG) complex that orchestrates SNARE-mediated tethering/fusion of vesicles that recycle the Golgi's glycosylation machinery results in severe glycosylation defects. Although two major Golgi v-SNAREs, GS28/GOSR1, and GS15/BET1L, are depleted in COG-deficient cells, the complete knockout of GS28 and GS15 only modestly affects Golgi glycosylation, indicating the existence of an adaptation mechanism in Golgi SNARE. Indeed, quantitative mass-spectrometry analysis of STX5-interacting proteins revealed two novel Golgi SNARE complexes-STX5/SNAP29/VAMP7 and STX5/VTI1B/STX8/YKT6. These complexes are present in wild-type cells, but their usage is significantly increased in both GS28- and COG-deficient cells. Upon GS28 deletion, SNAP29 increased its Golgi residency in a STX5-dependent manner. While STX5 depletion and Retro2-induced diversion from the Golgi severely affect protein glycosylation, GS28/SNAP29 and GS28/VTI1B double knockouts alter glycosylation similarly to GS28 KO, indicating that a single STX5-based SNARE complex is sufficient to support Golgi glycosylation. Importantly, co-depletion of three Golgi SNARE complexes in GS28/SNAP29/VTI1B TKO cells resulted in severe glycosylation defects and a reduced capacity for glycosylation enzyme retention at the Golgi. This study demonstrates the remarkable plasticity in SXT5-mediated membrane trafficking, uncovering a novel adaptive response to the failure of canonical intra-Golgi vesicle tethering/fusion machinery.


[Pathogenetic significance of hyperuricemia in the formation and development of pathological processes associated with metabolic syndrome].
This literature review allows to consider hyperuricemia as an important link in pathogenesis of cardiorenovascular pathologies, gout, diabetes, etc. The review contains detailed analysis of mechanisms of development of pathological processes caused by hyperuricemia, presentation of factors promoting elevation of uric acid level and description of direct effect of uric acid on organs and tissues.


Computational study of the reactivity of cytosine derivatives.
The aim of the present study is to provide computational insight using dispersion-corrected density-functional calculations into the reactivity properties of modified cytosine in the gas phase and in aqueous solution, whereby special emphasis is put on systems that are obtained through demethylation and methylation. Since this field is relatively incipient, our goal is to identify relationships between reactivity and stability for the modified compounds to understand their biological functionalities. Our results show that addition of a methyl, hydroxylmethyl, formyl, or carboxyl group reduces the length of the nearest hydrogen bond between the cytosine-guanine (CG) base pair and increases the length of the longest hydrogen bond of the DNA base pair. © 2017 Wiley Periodicals, Inc.


β-catenin-mediated YAP signaling promotes human glioma growth.
Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression.We and others find that YAP is up-regulated in human gliomas and associated with worse prognosis of patients. However, the role and mechanism of YAP in glioma progression is largely unknown. The expression of YAP in glioma tissues was detected by quantitative polymerase chain reaction (qPCR) and immunoblotting. The effect of YAP on glioma progression was examined using cell growth assays and intracranial glioma model. The effect of YAP on β-catenin protein level, subcellular location and transcription activity was examined by immunoblotting, immunofluorescence and RT-PCR. Firstly, knockdown of YAP inhibited glioma cell proliferation in vitro and tumor growth in vivo. In addition, YAP modulated the protein level, subcellular location and transcription activity of β-catenin via regulating the activity of GSK3β. Lastly, β-catenin partially mediated the effect of YAP on glioma cell proliferation. Our findings identify that YAP promotes human glioma growth through enhancing Wnt/β-catenin signaling. In addition, this study provides a new crosstalk mechanism between Hippo/YAP and Wnt/β-catenin pathways, which suggests a new strategy for human glioma treatment.


Autism spectrum disorder recurrence, resulting of germline mosaicism for a CHD2 gene missense variant.
Germline mosaicism for a novel missense variant p.Thr645Met located in the SNF2-related ATP dependent helicase domain of CHD2 in 2 affected siblings with autism spectrum disorder.


Ecological risk and source identifications of heavy metals contamination in the water and surface sediments from anthropogenic impacts of urban river, Indonesia.
Heavy metal pollution in urban rivers corresponds to anthropogenic impacts. Considering the environmental importance of the Winongo River for domestic use, agriculture, and fisheries, a comprehensive study of heavy metal contamination in this river needs to be conducted. This research focused on the assessment of heavy metal in the water and sediment using the enrichment factor (EF), geo-accumulation index (Igeo), Ecological Risk Index (Er), and Potential ecological risk index (RI). Results showed that the concentrations of the heavy metals Pb, Cu, Cd, Al, and Fe in the water samples exceeded thresholds. Based on EF, Igeo, and Er assessment, the level of contamination by the heavy metals Pb, Cu, Cr, and Cd was found to be low, and that by Fe and Al was found to be moderate to high. The mean values of heavy metals in sediment in the descending order are as follows Fe > Al > Pb > Cu > Cr > Cd (1,445, 2692.42, 0.17, 0.048, 0.016, 0 mg/kg) respectively. Meanwhile, the mean values of heavy metals in the water in descending were Al (1.208), Fe (0.857), Pb (0.155), Cu (0.018), Cr (0.009), and Cd (0 mg/L) respectively. The sources pollution of Cu, Cd, and Pb were identified as anthropogenic sources such as city effluent, road, fisheries, and mechanic workshops. Fe and Al from sediment exhibit strong correlation (r = 0.688). This suggests that Fe and Al possibly comes from same sources originating from earth materials. In general, the potential risk assessment showed that in the Winongo River, the midstream area had higher pollution levels than the downstream and upstream areas (pollution in midstream > downstream > upstream). The sources of pollution in the midstream were identified as city effluent, roads, fisheries, and mechanic workshops. For this reason, the findings of this research are expected to provide a scientific basis for pollution control.


In vitro biomechanical evaluation of fibular movement in below knee amputations.
In below knee amputations, the remaining fibula may be subjected to abnormal forces resulting in problematic tibia-fibular movement. The purpose of the current work was to examine the effect of amputation length and interosseous membrane integrity on fibular movement when subjected to unopposed biceps femoris muscle tension. Forty embalmed cadaveric specimens were subjected to a below knee amputation with fibular lengths of 5cm and 10cm. A subset of specimens (n=20) was further modified by sectioning the interosseous membrane. The tibias were mounted in a material testing machine and the biceps femoris was sutured to the actuator. Position-controlled tensile cyclic loading was applied (initial displacement of 4mm for 100 cycles at 0.5Hz with increments of 2mm up to 20mm) to the biceps femoris. The kinematics of the fibula with respect to the tibia was analyzed for three degrees of freedom: abduction, flexion and rotation. There was no interaction between below knee amputation length and interosseous membrane integrity on the degree of abduction, flexion, and rotation. However, below knee amputations with a sectioned interosseous membrane are abducted to a significantly greater degree than intact interosseous membrane below knee amputations. Furthermore, although embalmed specimens were tested here, embalming was consistent across specimens and it is unlikely that this confounded the findings. Understanding the cause of fibular abduction in below knee amputation will lead to recommendations for preventive surgical and rehabilitative measures.


Risk Factors for Complications after Reduction Mammoplasty: A Meta-Analysis.
Reduction mammoplasty (RM) is a proven method of treating macromastia, but the risk factors for postoperative complications have not been clearly identified. Through this meta-analysis, the authors aimed to identify the risk factors of RM complications. An extensive search of the literature describing complications after RM was performed using the PubMed Central, Embase, and Cochrane databases. The following risk factors were extracted: age, body mass index (BMI), tissue resection weight per breast (TRW), smoking and radiation therapy. Odds ratios (OR) were pooled with 95% confidence intervals (CI) to evaluate the relationship between these risk factors and complications after RM. A total of 16 unique studies including 10 593 patients were included in the final analysis. It showed that there was a significant difference in complications in BMI ≥30 kg/m2 (OR 0.73; 95% CI: 0.61-0.89, p = 0.001) and smoking (OR 1.56; 95% CI: 0.98-2.49, p = 0.06). Infection in those with BMI ≥30 kg/m2 showed a significant difference (OR 0.68; 95% CI: 0.52-0.89, p = 0.004), as well as wound dehiscence in smokers (OR 2.73; 95% CI: 1.60-4.67, p = 0.0002) and infection in irradiated breasts (OR 20.38; 95% CI: 3.42-121.35, p = 0.0009). However, there was no significant difference in age ≥50 years (OR 0.96; 95% CI: 0.71-1.29, p = 0.78), combined TRW ≥1000 g (OR 1.04; 95% CI: 0.43-2.50, p = 0.93). BMI ≥30 kg/m2 and smoking increase the risk of complications. Persons who are obese or irradiated are more likely to develop infections, and smokers experienced a higher incidence of wound dehiscence than did nonsmokers. However, patients aged ≥50 years and TRW ≥1000 g are not associated with complications from RM.


Endothelial dysfunction: The possible link between cardiovascular comorbidities and phenomenon of inflammaging from COPD.
Aging is a risk factor for many chronic noncommunicable diseases, including chronic obstructive pulmonary disease (COPD), which is often associated with cardiovascular disease (CVD). Moreover, aging is associated with a mild form of systemic inflammation. The aim of our study was to analyze the relationship between age, systemic and vascular inflammation, and the presence of CVD comorbidities in a stable COPD population. Forty COPD patients were divided into 2 age groups (<65 and ≥65 years of age), from which we collected the following inflammatory biomarkers: C-reactive protein, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and endothelin-1 (ET-1). Elderly COPD patients had more frequent exacerbation events per year (2 vs 1, P = .06), a higher prevalence of CVD (3 vs 2, P = .04), more limited exercise tolerance (6-minute walking test distance, 343 [283-403] vs 434 [384-484]; P = .02), and mild systemic inflammation (TNF-α, 9.02 [7.08-10.96] vs 6.48 [5.21-7.76]; P = .03; ET-1, 2.24 [1.76-2.71] vs 1.67 [1.36-1.98] pg/mL; P = .04). A weak correlation between age and ET-1 (r = 0.32, P = .04) was observed. Mild systemic inflammation, characterized by a slightly increased level of TNF-α, and endothelial dysfunction, marked by elevated ET-1, could be liaisons between aging, COPD, and CVD comorbidities.


Long-Term Cilostazol Treatment and Predictive Factors on Outcomes of Endovascular Intervention in Patients with Diabetes Mellitus and Critical Limb Ischemia.
Despite improvements in endovascular interventions and multidisciplinary approaches, improving clinical outcomes and increasing limb salvage have become increasingly challenging. This prospective study investigated the associations of cilostazol treatment with clinical outcomes and predictive factors in patients with diabetes mellitus (DM) and critical limb ischemia (CLI) after endovascular revascularization of the affected angiosome. In this study, 172 consecutive patients with CLI (Fontaine levels III-IV) received cilostazol treatment after successful endovascular intervention according to the angiosome concept, and their primary patency rates and cardiovascular and amputation events during a 24-month follow-up period were assessed. The 24-month primary patency rate, mortality rate, and amputation rate were better in the patients under long-term cilostazol treatment (P < 0.001, P = 0.029, and P = 0.014). Weighted multivariate Cox analyses with a propensity scoring-based method showed that long-term cilostazol treatment [hazard ratio (HR) 0.2, 95% confidence interval (CI) 0.11-0.36, P < 0.001], direct revascularization (DR) (HR 0.46, 95% CI 0.28-0.74, P = 0.002), and supervised exercise (HR 0.4, 95% CI 0.24-0.66, P < 0.001) were independently associated with primary patency. Patients with lower-extremity amputation (LEA) had a higher risk of coronary artery disease (CAD) and mortality. Cellulitis and neuropathy were independently associated with LEA events (cellulitis: HR 2.89, 95% CI 1.66-5.05, P < 0.001; neuropathy: HR 2.2, 95% CI 1.31-3.7, P = 0.003). Our results showed that patients with DM who received cilostazol treatment for more than 3 months had significantly better outcomes and decreased amputation and mortality rates after DR, and cellulitis and neuropathy were highly associated with the risk of limb loss. A large-scale randomized trial should be conducted in the future to confirm these results. Taipei Veterans General Hospital (TVGH) IRB no. 2013-08-020B. Registered 30 August 2013.


Thermal inactivation of Escherichia coli O157:H7 and Salmonella on catfish and tilapia.
Thermal inactivation kinetics of individual cocktails of Escherichia coli O157:H7, or of Salmonella meat isolates or seafood isolates were determined in catfish and tilapia. Determinations were done at 55, 60 and 65 °C using a circulating-water bath and calculated using linear regression analysis. Salmonella seafood and meat isolates D-10 values on the finfish were the same and ranged from 425 to 450, 27.1 to 51.4, 2.04-3.8 s (z = 4.3 °C) at 55, 60 and 65 °C, respectively. The E. coli O157:H7 D-10 values ranged from 422 to 564, 45.2 to 55.5 and 3.3-4.2 s (z = 4.3 °C) at 55, 60 and 65° C, respectively. The only statistical difference (P ≤ 0.05) was found when comparing the D-10 values for E. coli O157:H7 at 55 °C on catfish and tilapia. The other D-10 values for the Salmonella at all temperatures and E. coli O157:H7 at 60 and 65 °C on the catfish or tilapia showed no statistical difference. D-10 values for the catfish and tilapia were significantly lower than the reported values in other food systems, but the z-values were within the literature reported range. These D-10 values can be used to determine cooking parameters of finfish.


Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Understanding of the fundamental processes underlying the versatile clinical manifestations of COVID-19 is incomplete without comprehension of how different immune cells are recruited to various compartments of virus-infected lungs, and how this recruitment differs among individuals with different levels of disease severity. As in other respiratory infections, leukocyte recruitment to the respiratory system in people with COVID-19 is orchestrated by specific leukocyte trafficking molecules, and when uncontrolled and excessive it results in various pathological complications, both in the lungs and in other organs. In the absence of experimental data from physiologically relevant animal models, our knowledge of the trafficking signals displayed by distinct vascular beds and epithelial cell layers in response to infection by SARS-CoV-2 is still incomplete. However, SARS-CoV-2 and influenza virus elicit partially conserved inflammatory responses in the different respiratory epithelial cells encountered early in infection and may trigger partially overlapping combinations of trafficking signals in nearby blood vessels. Here, we review the molecular signals orchestrating leukocyte trafficking to airway and lung compartments during primary pneumotropic influenza virus infections and discuss potential similarities to distinct courses of primary SARS-CoV-2 infections. We also discuss how an imbalance in vascular activation by leukocytes outside the airways and lungs may contribute to extrapulmonary inflammatory complications in subsets of patients with COVID-19. These multiple molecular pathways are potential targets for therapeutic interventions in patients with severe COVID-19.


Psychological and neuropsychiatric implications of COVID-19.
COVID-19 infections have spread quickly, resulting in massive healthcare burden to societies worldwide. The most urgent interventions needed in the present climate include epidemiological measures to reduce the spread of infection, efficient treatment of patients with severe illness to reduce mortality rates, as well as development of diagnostic tests. Alongside this, the acute, medium, and long-term mental-health consequences of the COVID-19 outbreak for patients, their family members, medical professionals, and the public at large should not be underestimated. Here, we draw on evidence from previous coronavirus outbreaks (i.e., SARS, MERS) and emerging evidence from China, Europe, Asia and the US to synthesize the current knowledge regarding the psychological and neuropsychiatric implications of the COVID-19 pandemic.


Inspiratory Myoclonus.
Movement disorders of respiration are rare and are restricted to a phase of the respiratory cycle. The intermittent inspiratory myoclonus in this patient with post-anoxic encephalopathy is likely to be of brainstem origin. Rare movement disorders can be identified even in remote areas of the world where access to neurological care is limited.


Evaluation of a TB infection control implementation initiative in out-patient HIV clinics in Zambia and Botswana.
Out-patient human immunodeficiency virus (HIV) care and treatment clinics in Zambia and Botswana, countries with a high burden of HIV and TB infection. To develop a tuberculosis infection control (TB IC) training and implementation package and evaluate the implementation of TB IC activities in facilities implementing the package. Prospective program evaluation of a TB IC training and implementation package using a standardized facility risk assessment tool, qualitative interviews with facility health care workers and measures of pre- and post-test performance. A composite measure of facility performance in TB IC improved from 32% at baseline to 50% at 1 year among eight facilities in Zambia, and from 27% to 80% at 6 months among 10 facilities in Botswana. Although there was marked improvement in indicators of managerial, administrative and environmental controls, key ongoing challenges remained in ensuring access to personal protective equipment and implementing TB screening in health care workers. TB IC activities at out-patient HIV clinics in Zambia and Botswana improved after training using the implementation package. Continued infrastructure support, as well as monitoring and evaluation, are needed to support the scale-up and sustainability of TB IC programs in facilities in low-resource countries.


Effects of 1α,25-dihydroxyvitamin D3 on transport and metabolism of adefovir dipivoxil and its metabolites in Caco-2 cells.
Effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), natural ligand of the VDR, on the fates of adefovir dipivoxil (P-gp substrate) and its metabolites, mono(POM)-PMEA and adefovir (MRP4 substrate), were investigated in Caco-2 cells. After 1,25(OH)2D3-treatment, higher apical efflux of adefovir was observed after a 60 min incubation of adefovir divipoxil. Changes in these washout studies were predicted by a catenary model for the Caco-2 monolayer that described a higher MRP4 activity with 1,25(OH)2D3 treatment, as confirmed by Western blotting. Moreover, 1,25(OH)2D3 treatment (100 nM for 3 days) resulted in increased basolateral (B) to apical (A) (B-to-A) transport of adefovir dipivoxil but an unchanged A-to-B flux, rendering an elevated efflux ratio (EfR) (from 1.97 to 3.19). The EfR values in control and 1,25(OH)2D3-treated groups in these transport studies were reduced to 1.32 and 1.57, respectively, in the presence of verapamil (50 μM), the P-gp inhibitor. The B-to-A transport of the metabolite, adefovir, was increased in 1,25(OH)2D3-treated cells in the presence of verapamil, whereas the A-to-B and B-to-A transport of mono(POM)-PMEA remained unchanged. But the verapamil and 1,25(OH)2D3 treatments failed to alter rates of sequential metabolism of adefovir dipivoxil in cell lysate. The composite data established that 1,25(OH)2D3 treatment increased both P-gp and MRP4 transport activities without affecting the metabolism of adefovir dipivoxil by esterases. Moreover, an asymmetric appearance of metabolites, being higher with apical application, was observed. According to the catenary model, the asymmetry is suggestive that esterases are predominantly localized on the apical membrane and within the cell.


Effect of a new prostacyclin analogue on anastomosis of ischemic colon in dogs.
The effect of a new prostacyclin analogue OP-41483 on ischemic colonic anastomosis was investigated in dogs. Colonic ischemia was produced by devascularization of the marginal vessels in the left colon and graded into three degrees by measuring colonic blood flow with a hydrogen gas clearance method. The agent was administered intravenously after devascularization using a continuous infusion pump. The parameters studied were colonic blood flow in the submucosal layer, rate of anastomotic leakage, beta-glucuronidase activity and protein content of the colonic mucosa, and histologic changes. After administration of the agent, blood flow increased significantly and beta-glucuronidase activity at the anastomotic site was well preserved at a relatively high level in spite of ischemic change. The anastomotic leakage rate was significantly decreased. The present study proved that administration of this new prostacyclin analogue minimizes ischemic damage, and may be of considerable importance in ischemic colonic anastomoses.


Contact lens induced keratopathy: a severe complication extending the spectrum of keratoconjunctivitis in contact lens wearers.
A 21-year-old woman developed bilateral keratoconjunctivitis from contact lens wear, which progressed to diffuse corneal scarring and vascularization after the patient refused to discontinue wearing contact lenses. The visual disturbance became so severe that a penetrating keratoplasty had to be performed in one eye for visual rehabilitation. Examination of the penetrating keratoplasty specimen disclosed destruction of Bowman's membrane throughout the superior half of the cornea, which was replaced by a fibrous scar that was only midly chronically inflamed. Deep vascularization occurred within the stroma. This case represents an extreme expression of a recently characterized syndrome consisting of conjunctival and corneal changes in patients who may be allergic to contact lenses or the solutions used in conjunction with their care. In the milder end of the spectrum, there is superior epibulbar conjunctival injection with associated tarsal injection, and a mild superficial punctate keratopathy without filaments. Some earlier workers have termed this syndrome a variant of superior limbic keratoconjunctivitis in association with contact lens wear, but this leads to confusion with Theodore's classical superior limbic keratoconjunctivitis, to which the present entity bears no etiologic relationship; it also fails to show many of the findings of Theodore's disease. In mild cases, we would recommend the term contact lens-induced keratoconjunctivitis, and in the more severe cases, such as demonstrated by our patient, we would suggest the term contact lens-induced keratopathy.


Patients with malignant or potentially malignant ventricular arrhythmias: opportunities and limitations of drug therapy in prevention of sudden death.
Almost 90% of patients resuscitated from out of hospital cardiac arrest have coronary heart disease and can be categorized in one of three groups: acute myocardial infarction, ischemic event or primary arrhythmic event. The patients who have acute myocardial infarction have the best prognosis, and those with primary arrhythmic events have the worst. Recent studies show that ventricular arrhythmias after myocardial infarction are associated with mortality independent of any association with left ventricular dysfunction. Ventricular arrhythmias that have caused cardiac arrest or hemodynamic collapse, that is, malignant arrhythmias, should be treated aggressively and evaluated carefully with one of two methods that have high predictive accuracy for outcome: 1) the Holter recording/exercise test approach, or 2) the electrophysiologic approach. It is not yet known whether treating potentially malignant ventricular arrhythmias after myocardial infarction with class I or III antiarrhythmic drugs will reduce mortality, but two clinical trials are under way in the United States to address this question. Beta-adrenergic blocking drugs do reduce mortality, probably as a result of both antiischemic and antiarrhythmic effects. Calcium channel blocking agents, various antiplatelet drugs and alpha-adrenergic blocking drugs are under investigation to determine their value in secondary prevention of ventricular fibrillation.


Identification of a new locus, mus115, in Drosophila melanogaster.
Previous screens for autosomal genes that are necessary for resistance to DNA cross-linking agents but not to monofunctional agents have produced 6 mutations; all of which fall within the third chromosomal gene mus308. In an effort to identify analogous sex-linked genes, a screen of mutagenized X-chromosomes has been conducted for mutations that confer hypersensitivity to nitrogen mustard. This search has identified a new locus, mus115, through the recovery of a mutant that is strongly hypersensitive to nitrogen mustard but marginally sensitive to methyl methanesulfonate.


The integration of chemotherapy into the management of locally advanced cervical cancer: a pilot study.
Chemotherapy has been traditionally reserved as a last-time treatment for cervical cancer patients and in this setting long-term remissions are unusual. Platinum-based combination chemotherapy has been associated with high tumor response rates in patients with advanced and metastatic cervical tumors and past experience encouraged evaluation of chemotherapy as a first-line treatment in patients with locally advanced tumors where there is a high likelihood of relapse with local treatment. Thirty patients were treated initially with three courses of cis-platinum, vinblastine, and bleomycin with an overall response rate of 67%, and then had either radiotherapy or surgical resection. The initial results have been encouraging and the integration of chemotherapy into the management of locally advanced cervical cancer warrants further investigation.


Preparation of asymmetric, cerebroside sulfate-containing phospholipid vesicles.
A procedure is described which inserts asymmetrically cerebroside sulfate ('sulfatide') into the outer leaflet of bilayered phospholipid vesicles. Cerebroside sulfate is adsorbed onto a cellulose, filter-paper support and, when incubated with phosphatidylcholine vesicles is transferred to and inserted into the outer leaflet of these vesicles. This transfer occurs at, or above the transition temperature of the phospholipid and follows a similar pattern with small or larger ('fused') unilamellar vesicles. The transfer is linear with time for 1-2 h and is maximal after about 6 h, when the sulfatide content reaches about 6 mol% of the total quantity of phospholipid, corresponding to about 10 mol% of the phospholipids present in the outer layer. Initial rates of sulfatide transfer were somewhat increased when the vesicles contained a positively charged lipid (e.g. stearylamine) and decreased when this lipid was negatively charged (e.g. dicetyl phosphate) or hydrophobic (e.g. cholesterol). Divalent ions markedly inhibited sulfatide transfer and monovalent ions did so to a lesser degree. Once incorporated into the outer leaflet of the vesicle, the sulfatide could not be removed by washing with buffer, 1 M NaCl or 1 M urea.


Process analysis and modeling of a single-step lutein extraction method for wet microalgae.
Lutein is a commercial carotenoid with potential health benefits. Microalgae are alternative sources for the lutein production in comparison to conventional approaches using marigold flowers. In this study, a process analysis of a single-step simultaneous extraction, saponification, and primary purification process for free lutein production from wet microalgae biomass was carried out. The feasibility of binary solvent mixtures for wet biomass extraction was successfully demonstrated, and the extraction kinetics of lutein from chloroplast in microalgae were first evaluated. The effects of types of organic solvent, solvent polarity, cell disruption method, and alkali and solvent usage on lutein yields were examined. A mathematical model based on Fick's second law of diffusion was applied to model the experimental data. The mass transfer coefficients were used to estimate the extraction rates. The extraction rate was found more significantly related with alkali ratio to solvent than to biomass. The best conditions for extraction efficiency were found to be pre-treatment with ultrasonication at 0.5 s working cycle per second, react 0.5 h in 0.27 L/g solvent to biomass ratio, and 1:3 ether/ethanol (v/v) with 1.25 g KOH/L. The entire process can be controlled within 1 h and yield over 8 mg/g lutein, which is more economical for scale-up.


Late hematogenous seeding and infection of a femoropopliteal Omniflow II bypass.
Omniflow II is promoted as an infection-resistant vascular graft. It is used to treat vascular graft infection; nevertheless, early graft infection has been reported.Report: A 71-year-old patient was treated with an Omniflow II bypass for a non-healing diabetic foot ulcer. Seven months postoperatively, late infection occurred secondary to hematogenous spread from a persistent foot infection. We report on the first case of late infection of an Omniflow II vascular graft caused by hematogenous spread. Despite promising results of the Omniflow II graft in the treatment of vascular graft infection, late infection may not be avoided.


Noncoding RNA and colorectal cancer: its epigenetic role.
The use of novel sequencing and high-throughput techniques has become widespread, and are now readily available to obtain the comprehensive transcription profile of the human genome. Noncoding RNAs (ncRNAs) are transcripts that have no apparent protein-coding capacity, but they have important roles in human physiology. Most research in this area has focused on micro-RNAs. However, the role of long ncRNAs (lncRNAs) as drivers of tumor suppression and oncogenic functions has recently been examined in numerous cancer types. Epigenetic alterations can reportedly deregulate the expression of any type of transcript. However, the exact mechanisms of epigenetic regulation of lncRNA are still unknown. In this review, the authors primarily focus on the epigenetic effects modulating ncRNA in colorectal cancer (CRC). The authors specifically discuss examples of oncogenic ncRNA in CRC pathobiology, as well as its extended diagnosis, prognosis and therapy.


Design of VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1): A double-blind, randomized placebo-controlled trial of COVID-19 convalescent plasma in hospitalized patients with early respiratory compromise.
Effective therapeutics for severe acute respiratory syndrome CoronaVirus-2 (SARS-CoV-2) infection are evolving. Under Emergency Use Authorization, COVID-19 convalescent plasma (CCP) was widely used in individuals hospitalized for COVID-19, but few randomized controlled trials supported its efficacy to limit respiratory failure or death. VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1) was a double-blind, multi-site, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of CCP with conventional therapy in hospitalized Veterans with SARS-CoV-2 infection and early respiratory compromise (requirement for oxygen). Participants (planned sample size 702) were randomized 1:1 to receive CCP with high titer neutralizing activity or 0.9% saline, stratified by site and age (≥65 versus <65 years old). Participants were followed daily during initial hospitalization and at Days 15, 22 and 28. The composite primary outcome was acute hypoxemic respiratory failure or all-cause death by Day 28. Secondary outcomes by day 28 included time-to-recovery, clinical severity, mortality, rehospitalization for COVID-19, and adverse events. Serial respiratory and blood samples were collected for safety, virologic and immunologic analyses and future studies. Key variables in predicting the success of CURES-1 were: (1) enrollment early in the course of severe infection; (2) use of plasma with high neutralizing activity; (3) reliance on unambiguous, clinically meaningful outcomes. CURES-1 was terminated for futility due to perceived inability to enroll in the lull between the Alpha and Delta waves of the SARS CoV-2 epidemic. VA CURES-1 was a large multi-site trial designed to provide conclusive information about the efficacy of CCP in well-characterized patients at risk for progression of COVID-19. It utilized a rigorous study design with relevant initial timing, quality of product and outcomes. ClinicalTrials.gov Identifier: NCT04539275.


Primate genotyping via high resolution melt analysis: rapid and reliable identification of color vision status in wild lemurs.
Analyses of genetic polymorphisms can aid our understanding of intra- and interspecific variation in primate sociality, ecology, and behavior. Studies of primate opsin genes are prime examples of this, as single nucleotide variants (SNVs) in the X-linked opsin gene underlie variation in color vision. For primate species with polymorphic trichromacy, genotyping opsin SNVs can generally indicate whether individual primates are red-green color-blind (denoted homozygous M or homozygous L) or have full trichromatic color vision (heterozygous ML). Given the potential influence of color vision on behavior and fitness, characterizing the color vision status of study subjects is becoming commonplace for many primate field projects. Such studies traditionally involve a multi-step sequencing-based method that can be costly and time-consuming. Here we present a new reliable, rapid, and relatively inexpensive method for characterizing color vision in primate populations using high resolution melt analysis (HRMA). Using lemurs as a case study, we characterized variation at exons 3 and/or 5 of the X-linked opsin gene for 87 individuals representing nine species. We scored opsin genotypes and color vision status using both traditional sequencing-based methods as well as our novel melting-curve based HRMA protocol. For each species, the melting curves of varying genotypes (homozygous M, homozygous L, heterozygous ML) differed in melting temperature and/or shape. Melting curves for each sample were consistent across replicates, and genotype-specific melting curves were consistent across DNA sources (blood vs. feces). We show that opsin genotypes can be quickly and reliably scored using HRMA once lab-specific reference curves have been developed based on known genotypes. Although the protocol presented here focuses on genotyping lemur opsin loci, we also consider the larger potential for applying this approach to various types of genetic studies of primate populations.