Identification of Specific Endobronchial Ultrasound Features to Differentiate Sarcoidosis From Other Causes of Lymphadenopathy.
We hypothesized that specific endobronchial ultrasound (EBUS) features may differentiate sarcoidosis from other causes of lymphadenopathy. We conducted this retrospective observational study from January 2014 to January 2019 to analyze patients with intrathoracic lymphadenopathy who underwent EBUS-guided transbronchial needle aspiration. Ultrasound features, including nodal size, margin, echogenicity, the presence or absence of calcification, a central hilar structure, the coagulation necrosis sign, nodal conglomeration, and the septal vessel sign in the color Doppler mode were recorded and compared between 3 groups. Of the 90 included patients, 15 had a diagnosis of tuberculosis; 56 had a diagnosis of sarcoidosis; and 19 had a diagnosis of malignant lymph nodes by EBUS-guided transbronchial needle aspiration. The presence of nodal conglomeration (94.6% versus 60.0% versus 5.3%; P < .001), the septal vessel sign in the color Doppler mode (55.4% versus 13.3% versus 15.8%; P = .002), and a distinct margin (73.2% versus 13.3% versus 47.4%; P < .001) were significantly higher in the sarcoidosis group than in the tuberculosis lymphadenopathy and malignant lymph node groups. The presence of the coagulation necrosis sign (8.9% versus 93.3% versus 31.6%; P < .001) was significantly lower in the sarcoidosis group than in tuberculosis lymphadenopathy and malignant lymph node groups. A multivariate analysis showed that the presence of nodal conglomeration, the absence of coagulation necrosis, and the presence of the septal vessel sign in the color Doppler mode were independent predictive factors for the diagnosis of sarcoidosis. The presence of nodal conglomeration, the absence of coagulation necrosis, and the presence of the septal vessel sign in the color Doppler mode in lymph nodes on EBUS are predictive of sarcoidosis.


The effect of electrical stimulation on post mortem myofibrillar protein degradation and small heat shock protein kinetics in bull beef.
This study aimed to determine the effect of electrical stimulation and ultimate pH (pHu) on shear force, myofibrillar protein degradation and small heat shock protein (sHSP) concentrations in M. longissimus lumborum (LL). The LL from both sides of carcasses (n=15) was excised with low voltage electrical stimulation (ES) applied to an LL muscle from one side, while the opposing LL muscle was not stimulated (NS). Muscles were categorised into low (pHu<5.8), intermediate (5.8≤pHu<6.2) and high pHu (pHu≥6.2) and aged for up to 28days post mortem at -1.5°C. High pHu meat tenderised faster which corresponded with the faster degradation of titin and desmin in this group compared with low and intermediate pHu meat. Electrical stimulation significantly affected the variable levels of αβ-crystallin and HSP20 with higher concentrations of these sHSP in ES muscles at later ageing timepoints compared with NS muscles.


A gene required for nuclear and mitochondrial attachment in the nematode Caenorhabditis elegans.
Nuclei occupy characteristic positions in most cells. In Caenorhabditis elegans, nuclei can be observed in living animals. Ordinary movements can distort the cells and displace their nuclei, but the extent of displacement is limited and nuclei return to their resting positions when the muscles relax. We have isolated five mutants in which the nuclei of certain epithelial cells are not elastically anchored but float freely within the cytoplasm. These mutations define a single gene, anc1, on linkage group 1. Mitochondrial positioning, observed by staining live animals with rhodamine 6G, is also disturbed in these cells. Additional defects, including abnormal tonofilaments and inappropriately positioned desmosomes, have been found by electron microscopy. The anc1 product may be a cytoskeletal component of nematode epithelial cells. Although the Anc1 phenotype is fully expressed in the newly hatched larvae, mutants develop and reproduce normally. Despite mispositioning of organelles, cuticle deposition and moulting are essentially normal. These mutations represent the null phenotype of the gene. At least three independent isolates revert spontaneously at high frequency (10(-5) to 10(-4) ). We suggest that anc1 is a member of a family of cytoskeletal genes.


Bringing research to the intensive care setting.
Dr. Deborah J. Cook's contributions in the field of critical care have not only impacted the intensive care unit (ICU) patients she treats and countless others worldwide but have also helped establish research programs and clinical trials as integral components of improving care and outcomes for the most seriously ill. Lara Szewczak spoke with Dr. Cook, recipient of the 2022 Canada Gairdner Wightman award, about critical care research, her reflections on the COVID-19 pandemic, and her views on mentorship. An edited version of this conversation is presented below.


Evaluation of a microcomputer-based clinical laboratory data acquisition system linked with a minicomputer-based patient data management system.
We describe a microcomputer-based clinical laboratory data acquisition system linked with a minicomputer-based patient data management system and report on its performance. The system consists of a microcomputer and six laboratory analyzers: a blood gas analyzer, a flame photometer, a plasma osmotic pressure meter, a chloride ion titrator, a blood sugar analyzer, and a hemoglobin concentration and saturation meter. With the addition of a previously developed microinterface unit to each laboratory analyzer, data from each analyzer can be automatically transmitted to the microcomputer through a communication network. These data are then automatically transmitted to the patient data management system and thereby become part of that data base. Performance of this system was evaluated in two ways: (1) by comparing the turnaround time from an anesthetist's order for a laboratory analysis to receipt of the analysis with the time required in a control situation and (2) by comparing the number of steps a laboratory technician is required to walk to obtain and deliver the laboratory result with the number of steps required in a control situation in which no system was used. The turnaround time and the number of steps walked using this system were 552 +/- 41 seconds (n = 19, P less than 0.001) and 197 +/- 31 steps, respectively (n = 19, P less than 0.001), contrasted with 622 +/- 52 seconds and 374 +/- 87 steps without the system.


Caffeine, tobacco, alcohol and drug consumption among medical students in Barcelona.
A survey of medical students was conducted at the Universitat Autònoma de Barcelona in 1974. Out of 1029 students, 808 present at lectures (78.5%) returned properly completed questionnaires. These showed that mean caffeine consumption was 8.3 g per month and increased with the length of stay at the university. Tobacco consumption (general mean, 190 cigarettes per month, 216 for males and 150 for females) and alcohol consumption (8.8 litres/year for males and 4.1 litres/year for females) also increased with time spent at university. Alcohol consumption was not as high as in the general population. Amphetamine consumption was very high (22% of students had taken amphetamines on more than one occasion in the six months prior to the survey). Marihuana and hashish were by far the most commonly used drugs (9.6%), the use of these drugs being much less common than at other European universities. The use of "harder" drugs was very limited. Appraisal of alcohol, tobacco and amphetamine abuse is necessary, since the authorities have not employed adequate measures to stop or limit them.


Targeted next generation sequencing of RB1 gene for the molecular diagnosis of Retinoblastoma.
The spectrum of RB1gene mutations in Retinoblastoma (RB) patients and the necessity of multiple traditional methods for complete variant analysis make the molecular diagnosis a cumbersome, labor-intensive and time-consuming process. Here, we have used targeted next generation sequencing (NGS) approach with in-house analysis pipeline to explore its potential for the molecular diagnosis of RB. Thirty-three patients with RB and their family members were selected randomly. DNA from patient blood and/or tumor was used for RB1 gene targeted sequencing. The raw reads were obtained from Illumina Miseq. An in-house bioinformatics pipeline was developed to detect both single nucleotide variants (SNVs) and small insertions/deletions (InDels) and to distinguish between somatic and germline mutations. In addition, ExomeCNV and Cn. MOPS were used to detect copy number variations (CNVs). The pathogenic variants were identified with stringent criteria, and were further confirmed by conventional methods and cosegregation in families. Using our approach, an array of pathogenic variants including SNVs, InDels and CNVs were detected in 85% of patients. Among the variants detected, 63% were germline and 37% were somatic. Interestingly, nine novel pathogenic variants (33%) were also detected in our study. We demonstrated for the first time that targeted NGS is an efficient approach for the identification of wide spectrum of pathogenic variants in RB patients. This study is helpful for the molecular diagnosis of RB in a comprehensive and time-efficient manner.


Plasticity of the synaptic contact zone following loss of synapses in the cerebral cortex of aging humans.
Quantitative ultrastructural analyses of ethanolic phosphotungstic acid-stained human layer 1 precentral motor cortex (Brodmann's area 4) and layer 1 postcentral somatosensory cortex (Brodmann's area 3) were undertaken to determine the nature of synaptic changes occurring over a series of ages (45-84 years) of a normal aging human population. In the precentral cortex, a significant decrease in the number of synapses was accompanied by an increase in mean length of the postsynaptic contact zone and a decrease in the mean width of the presynaptic paramembranous density. The frequency of mature type A and immature type E synaptic profiles decreased with age. There were no changes in the width of the postsynaptic paramembranous density, cleft width or the number of presynaptic dense projections per synapse. In the postcentral cortex there were no significant changes in synaptic number or in any of the synaptic parameters measured. The present study demonstrates that age-related synapse loss in the human cerebral cortex may be confined to specific cortical regions. The data suggest that in the precentral cortex the plasticity of the synaptic contact zone may be a compensatory response by the remaining synapses to age-related synapse loss.


New barrier attire regulations in the operating room: A mandate without basis?
Recent AHRQ/Joint Commission guidelines mandate additional barrier attire for all operating room personnel to target infection. The scientific basis for this is unclear. Patients undergoing abdominal surgery at our institution were identified from institutional NSQIP database before and after March 2016, when guidelines were implemented. Patient-level variables were compared for the pre- and post-implementation groups. Multivariable regression evaluated associations between implementation and surgical site infection (SSI) and other outcomes. 1122 patients (including 60.9% laparoscopic and 16.4% bowel resection procedures) were included. There were 607 patients post-implementation and 515 pre-implementation; cohorts were similar in risk factors for SSI. Fifty-seven patients developed SSI. On multivariable analysis, laparoscopy, bowel resection and operating duration, but not barrier attire, were associated with SSI. Implementation of attire did not significantly impact SSI (p = 0.4), hospital readmission (p = 0.4), or reoperation (p = 0.9). These data question the rationale for the new more stringent operating room attire guidelines which burden hospitals with additional cost, time and resources, and could detract efforts to target important factors that really influence outcomes.


The section-Golgi impregnation procedure. 2. Immunocytochemical demonstration of glutamate decarboxylase in Golgi-impregnated neurons and in their afferent synaptic boutons in the visual cortex of the cat.
Sections of the cat's visual cortex were stained by an antiserum to glutamate decarboxylase using the peroxidase-antiperoxidase method; they were then impregnated by the section Golgi procedure and finally the Golgi deposit was replaced by gold. Neurons containing glutamate decarboxylase immunoreactivity were found in all layers of the visual cortex, without any obvious pattern of distribution. Fifteen immunoreactive neurons were also Golgi-impregnated and gold-toned, which enabled us to study the morphology and synaptic input of identified GABAergic neurons. These neurons were found to be heterogeneous both with respect to the sizes and shapes of their perikarya and the branching patterns of their dendrites. All the immunoreactive, Golgi-impregnated neurons had smooth dendrites, with only occasional protrusions. The synaptic input of glutamate decarboxylase-immunoreactive neurons was studied in the electron microscope. Immunoreactive neurons received immunoreactive boutons forming symmetrical synapses on their cell bodies. The Golgi-impregnation made it possible to study the input along the dendrites of immunoreactive neurons. One of the large neurons in layer III whose soma was immunoreactive was also Golgi-impregnated: it received numerous non-immunoreactive asymmetrical synaptic contacts along its dendrites and occasional ones on its soma. The same neuron also received a few boutons forming symmetrical synaptic contacts along its Golgi-impregnated dendrites; most of these boutons were immunoreactive for glutamate decarboxylase. Glutamate decarboxylase-immunoreactive boutons were also found in symmetrical synaptic contact with non-immunoreactive neurons that were Golgi-impregnated. A small pyramidal cell in layer III was shown to receive several such boutons along its somatic membrane. It is concluded that the combination of immunoperoxidase staining and Golgi impregnation is technically feasible and that it can provide new information. The present study has shown that there are many morphologically distinct kinds of aspiny GABAergic neurons in the visual cortex; that the predominant type of synaptic input to the dendrites of such neurons is from boutons forming asymmetrical synapses, but that some of the GABAergic neurons also receive a dense symmetrical synaptic input on their cell bodies, and occasional synapses along their dendrites, from the boutons of other GABAergic neurons. These findings provide a morphological basis, firstly, for a presumed powerful excitatory input to GABAergic interneurons and, secondly, for the disinhibition which has been postulated from electrophysiological studies to occur in the cat's visual cortex.


Mobility indices and doses from 210Po and 210Pb activity concentrations data in Brazilian spas groundwaters.
210Po and 210Pb activity concentrations in spas groundwaters occurring at São Paulo (SP) and Minas Gerais (MG) states, Brazil, have been reported in this paper with a dual purpose: to compare different indices for evaluating the radionuclides mobility into waters and to evaluate the drinking water quality from dose calculations. The waters (75 sampling points) are extensively used for drinking in public places, bottling and bathing purposes, among other. The samples were taken from springs and wells drilled at different aquifer systems inserted in Paraná and Southeastern Shield hydrogeological provinces. The WHO guideline reference value for 210Pb and 210Po of 0.1 Bq/L in drinking water was not reached for 210Pb but the 210Po levels were equal or above it in four spas groundwaters from MG State. The maximum WHO guidance dose level of 0.1 mSv/yr was also reached or surpassed in them. The 210Pb "mobility index" taking into account the ratio of the weight of the dissolved 210Pb per unit volume of solution to its weight per unit weight of the rock matrix yielded values in the range of 0.01-5.2 kg/m3. Another "mobility index" (Preference Ratio) expressing the ratio of 210Pb and 238U in the waters divided by the ratio of 210Pb and 238U in the rock matrices provided values between 0.004 and 7994. The 210Pb/238U activity ratios of some spas groundwaters suggested preferential 238U transport relative to 210Pb into the liquid phase, whereas the ratio of the 210Pb to 238U mobility indices indicated the opposite. Such finding showed a better usefulness of the mobility indices for evaluating processes affecting the radionuclides release into the liquid phase during the water/rock interactions.


MicroRNA profiling during human keratinocyte differentiation using a quantitative real-time PCR method.
The terminal differentiation of epidermal keratinocytes requires transcriptional and posttranscriptional regulatory mechanisms. MicroRNAs (miRNAs) are small noncoding RNAs that play key roles during differentiation processes by regulating protein expression at the posttranscriptional level. Several studies have investigated miRNA expression in murine or human skin using northern blotting, microarrays, deep sequencing, or real-time PCR (Andl et al., Curr Biol 16:1041-1049, 2006; Hildebrand et al., J Invest Dermatol 131:20-29, 2011; Sonkoly et al., PLoS One 2:e610, 2007; Yi et al., Nat Genet 38:356-362, 2006; Yi et al., Proc Natl Acad Sci U S A 106:498-502, 2009). Conventional techniques such as northern blotting and microarrays often fail to detect miRNAs of low abundance, while the per-sample cost of deep sequencing approaches is still prohibitive in many cases. In contrast, stem loop primer-based real-time PCR methods for simultaneous detection of up to 380 miRNAs allow fast, specific, and reliable miRNA profiling. These methods are suitable for in vitro material, but also for samples which are of limited availability, such as epidermal stem cells isolated from human skin biopsies. Here, we describe a general real-time PCR method for miRNA profiling using isolated epidermal stem cells, transiently amplifying cells and terminally differentiated keratinocytes of human skin.


Tracking volcanic explosions using Shannon entropy at Volcán de Colima.
The main objective of this work is to show that Shannon Entropy (SE) calculated on continuous seismic signals can be used in a volcanic eruption monitoring system. We analysed three years of volcanic activity of Volcán de Colima, México, recorded between January 2015 and May 2017. This period includes two large explosions, with pyroclastic and lava flows, and intense activity of less energetic explosion, culminating with a period of quiescence. In order to confirm the success of our results, we used images of the Visual Monitoring system of Colima Volcano Observatory. Another of the objectives of this work is to show how the decrease in SE values can be used to track minor explosive activity, helping Machine Learning algorithms to work more efficiently in the complex problem of distinguishing the explosion signals in the seismograms. We show that the two big eruptions selected were forecasted successfully (6 and 2 days respectively) using the decay of SE. We conclude that SE could be used as a complementary tool in seismic volcano monitoring, showing its successful behaviour prior to energetic eruptions, giving time enough to alert the population and prepare for the consequences of an imminent and well predicted moment of the eruption.


Porous silicon biosensor for detection of viruses.
There is a growing need for virus sensors with improved sensitivity and dynamic range, for applications including disease diagnosis, pharmaceutical research, agriculture and homeland security. We report here a new method for improving the sensitivity for detection of the bacteriophage virus MS2 using thin films of nanoporous silicon. Porous silicon is an easily fabricated material that has extremely high surface area to volume ratio, making it an ideal platform for surface based sensors. We have developed and evaluated two different methods for covalent bioconjugation of antibodies inside of porous silicon films, and we show that the pore penetration and binding efficiency depend on the wettability of the porous surface. The resulting films were used to selectively capture dye-labeled MS2 viruses from solution, and a viral concentration as low as 2 x 10(7) plaque-forming units per mL (pfu/mL) was detectable by measuring the fluorescence from the exposed porous silicon film. The system exhibits sensitivity and dynamic range similar to the Luminex liquid array-based assay while outperforming protein micro-array methods.


Approaches towards fighting the COVID‑19 pandemic (Review).
The coronavirus disease 2019 (COVID‑19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in recent years. Infection with COVID‑19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID‑19, SARS‑CoV‑2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID‑19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID‑19, characterizes the SARS‑CoV‑2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of anti‑SARS‑CoV‑2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID‑19 is discussed. It is expected that novel anti‑viral agents, vaccines or an effective combination therapy for treatment/management of SARS‑CoV‑2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against COVID‑19.


Kinematics of the head and associated vertebral artery length changes during high-velocity, low-amplitude cervical spine manipulation.
Cervical spine manipulation (CSM) is a frequently used treatment for neck pain. Despite its demonstrated efficacy, concerns regarding the potential of stretch damage to vertebral arteries (VA) during CSM remain. The purpose of this study was to quantify the angular displacements of the head relative to the sternum and the associated VA length changes during the thrust phase of CSM. Rotation and lateral flexion CSM procedures were delivered bilaterally from C1 to C7 to three male cadaveric donors (Jan 2016-Dec 2019). For each CSM the force-time profile was recorded using a thin, flexible pressure pad (100-200 Hz), to determine the timing of the thrust. Three dimensional displacements of the head relative to the sternum were recorded using an eight-camera motion analysis system (120-240 Hz) and angular displacements of the head relative to the sternum were computed in Matlab. Positive kinematic values indicate flexion, left lateral flexion, and left rotation. Ipsilateral refers to the same side as the clinician's contact and contralateral, the opposite. Length changes of the VA were recorded using eight piezoelectric ultrasound crystals (260-557 Hz), inserted along the entire vessel. VA length changes were calculated as D = (L1 - L0)/L0, where L0 = length of the whole VA (sum of segmental lengths) or the V3 segment at CSM thrust onset; L1 = whole VA or V3 length at peak force during the CSM thrust. Irrespective of the type of CSM, the side or level of CSM application, angular displacements of the head and associated VA length changes during the thrust phase of CSM were small. VA length changes during the thrust phase were largest with ipsilateral rotation CSM (producing contralateral head rotation): [mean ± SD (range)] whole artery [1.3 ± 1.0 (- 0.4 to 3.3%)]; and V3 segment [2.6 ± 3.6 (- 0.4 to 11.6%)]. Mean head angular displacements and VA length changes were small during CSM thrusts. Of the four different CSM measured, mean VA length changes were largest during rotation procedures. This suggests that if clinicians wish to limit VA length changes during the thrust phase of CSM, consideration should be given to the type of CSM used.


Low-turnover bone disease in hypercalcemic hyperparathyroidism after kidney transplantation.
Hypercalcemia in persistent secondary hyperparathyroidism after kidney transplantation is considered to result from increased bone resorption. Bone biopsies' studies, however, have never been performed in these patients. Bone biopsies after double tetracycline labeling were obtained from 17 patients with hypercalcemic hyperparathyroidism and an estimated glomerular filtration rate > 30 mL/min/1.73 m2. Serologic bone markers, calcitriol, intact fibroblast growth factor-23 (iFGF-23), and serum and 24h urine concentration of calcium and phosphate were measured in all patients. Tubular maximum for phosphate corrected for GFR (TmP/GFR), and the fractional excretion of calcium (FeCa) were calculated. High-turnover renal osteodystrophy (ROD) was present in nine and low-turnover ROD in eight patients. The bone formation rate was significantly associated with bone alkaline phosphatase, c-telopeptide and osteocalcin. In patients with high turnover ROD, osteocalcin was also significantly higher than in patients with decreased bone formation. The FeCa was normal or below normal in 14/17 patients. TmP/GFR was below normal in all patients. Neither intact PTH nor iFGF-23 was associated with TmP/GFR, FeCa or any histomorphometric bone parameter. We conclude that hypercalcemia of posttransplant hyperparathyroidism can be associated with high or low turnover bone disease. Decreased calcium excretion suggests an additive tubular effect on hypercalcemia.


Cow's urine poisoning in Nigeria: cardiorespiratory effects of cow's urine in dogs.
"Cow's urine" concoction (CUPR) is a traditional remedy for convulsive seizures in Nigeria. Its administration has been associated with severe poisoning, sometimes with a fatal outcome in Nigerian children. Recently, we showed that several of the components of the concoction are toxic. We have demonstrated in the present study certain cardio-respiratory effects of cow's urine concoction in dogs. On the cardiovascular system, an initial bradycardia followed by tachycardia and a biphasic effect on blood pressue characterized by a fall followed by a rise were demonstrated. Progressive hypotension following repreated administration of CUPR was also shown in all experimental dogs. On the respiratory system, a short period of respiratory arrest and/or respiratory depression, followed by tachyponoea with associated hypoventilation of the lungs, were observed. The possible explanations for the observed cardiorespiratory effects of the concoction were discussed. On the basis of our findings, an hypothesis is advanced for the possible mechanisms of the neurological sequelae and/or death following cow's urine poisoning.


Regeneration across preserved peripheral nerve grafts.
The potential to store nerve grafts for a prolonged period of time was assessed in a rat sciatic nerve model. Three-centimeter syngeneic nerve grafts were stored in Belzer/University of Wisconsin cold storage solution at different temperatures (5 degrees C, 22 degrees C, or 37 degrees C) for varying time periods (6 h, 24 h, or 3 weeks) prior to transplantation. Functional assessment using serial walking track analyses revealed no difference between storage times and temperatures. At 14 months postengraftment, the conduction velocities and the number of myelinated fibers that had regenerated across all grafts stored at 5 degrees C for all time periods tested were superior to grafts stored at either 22 degrees C or 37 degrees C. Nerve grafts stored for up to 3 weeks at 5 degrees C acted as effective conduits for proximal regenerating fibers and resulted in histologic, electrophysiologic, and functional results equivalent to fresh nerve grafts. Nerve graft storage may be applicable to nerve allografts and potentially provide allograft material that requires reduced or no associated host immunosuppression.


Single atom substitution in mouse protein kinase G eliminates oxidant sensing to cause hypertension.
Blood pressure regulation is crucial for the maintenance of health, and hypertension is a risk factor for myocardial infarction, heart failure, stroke and renal disease. Nitric oxide (NO) and prostacyclin trigger well-defined vasodilator pathways; however, substantial vasorelaxation in response to agents such as acetylcholine persists when the synthesis of these molecules is prevented. This remaining vasorelaxation activity, termed endothelium-derived hyperpolarizing factor (EDHF), is more prevalent in resistance than in conduit blood vessels and is considered a major mechanism for blood pressure control. Hydrogen peroxide (H2O2) has been shown to be a major component of EDHF in several vascular beds in multiple species, including in humans. H2O2 causes the formation of a disulfide bond between the two α subunits of protein kinase G I-α (PKGI-α), which activates the kinase independently of the NO-cyclic guanosine monophosphate (cGMP) pathway and is coupled to vasodilation. To test the importance of PKGI-α oxidation in the EDHF mechanism and blood pressure control in vivo, we generated a knock-in mouse expressing only a C42S 'redox-dead' version of PKGI-α. This amino acid substitution, a single-atom change (an oxygen atom replacing a sulfur atom), blocked the vasodilatory action of H2O2 on resistance vessels and resulted in hypertension in vivo.


Differential signalling mechanisms predisposing primary human skeletal muscle cells to altered proliferation and differentiation: roles of IGF-I and TNFalpha.
To gain a clearer insight into the mechanisms of skeletal muscle cell growth, differentiation and maintenance, we have developed a primary adult human skeletal muscle cell model. Cells were cultured from biopsies of rectus muscle from the anterior abdominal wall of patients undergoing elective surgery. Under differentiating conditions, all cultures formed myotubes, irrespective of initial myoblast number. Stimulation with both IGF-I and tumour necrosis factor alpha (TNFalpha) increased cellular proliferation but while IGF-I subsequently increased myoblast differentiation, via both hyperplasia and hypertrophy, TNFalpha inhibited the initiation of differentiation, but did not induce apoptosis. Addition of IGF-I stimulated both the MAP kinase and the phosphatidylinositide 3-kinase (PI 3-kinase) signalling pathways while treatment with TNFalpha preferentially led to MAP kinase activation although with a very different profile of activation compared to IGF-I. Data using the MEK inhibitor UO126 showed MAP kinase activity is not only needed for cellular proliferation but is also necessary for both the initiation and the progression of primary human myoblast differentiation. The PI 3-kinase pathway is also involved in differentiation, but activation of this pathway could not relieve inhibition of differentiation by TNFalpha or UO126. Our results show that the controlled temporal and amplitude of activation of multiple signalling pathways is needed for successful myoblast differentiation.


Role of glutathione in the aerobic radiation response.
We will review the relationships between glutathione (GSH), protein thiols, and cellular responses to radiation, peroxides, and peroxide-producing drugs. Our primary interest involves the behavior of sulfhydryls as electron and hydrogen carriers, and their capacity to protect various target molecules against radiation and peroxidative damage. We used reagents such as L-buthionine sulfoximine (LBSO), alone and in combination with N-ethyl maleimide (NEM), diamide, and dimethylfumarate, to decrease GSH so that it could no longer participate in the electron transfer reactions. Our results indicate that aerobic sensitization produced by GSH depletion can be further enhanced if electron-accepting agents, such as tertiary butyl hydroperoxide (t-BOOH), are present during irradiation. Hydroperoxide is a substrate for glutathione peroxidase and diverts electrons and hydrogen away from target molecules during its reduction. Sensitivity to radiation seems to be due to the inhibition of the mitochondria's capacity to reduce hydroperoxide. We will also report the mitochondria's ability to reduce the oxygen radicals produced by radiation and drugs. Data also indicate that t-BOOH oxidizes protein thiols which are enzymatically involved in repair of DNA damage.


Development of Novel Indole Molecules for the Screening of Anti-Inflammatory Activity.
In the present work, some new 5-[2(3)-dialkylamino alkoxy] Indole 2,3-diones were prepared from 5-hydroxy isatin. A mixture of 5-hydroxy isatin, dialkylamino alkylhalide in alcoholic potassium hydroxide was stirred at room temperature for 6 h to get the 5-[2(3)-dialkylamino alkoxy] Indole 2,3-diones. The structures of the products were characterized by IR, NMR, MASS Spectral studies. All the compounds were evaluated for anti-inflammatory activity. Some of these compounds showed good anti-inflammatory activity compared with standard compound Indomethacin.


Recent Recommendations for Management of Human Immunodeficiency Virus-Positive Patients.
Human immunodeficiency virus (HIV) infection has become a chronic condition. HIV is not a valid reason to deny, delay, or withhold dental treatment. There are no absolute contraindications and few complications associated with comprehensive oral health care treatment delivered in an outpatient setting for asymptomatic HIV-infected patients and clinically stable patients with AIDS. Consultation with the patient's medical provider and modifications in the delivery of dental treatment may be necessary when treating patients with advanced HIV disease or other comorbid conditions. Oral health care is an integral and important part of comprehensive health care for all patients with HIV/AIDS.


[Pituitary necrosis and antiphospholipid syndrome].
Antiphospholipid syndrome (APS) is an acquired thrombotic disorder. It mainly occurs with systemic disease or as a primary disorder. All organs may be involved by thrombosis, but to date the most common endocrine manifestation is chronic adrenal insufficiency. Very few cases of hypopituitarism with primary APS have been reported. We report the case of a 27-year-old woman, victim of a stroke leading to double vision and intracranial hypertension. Magnetic resonance imaging showed a macro-adenoma with hemorrhage of a suprasellar lesion. Hormone assessment showed hyper prolactinemia with positive anticardiolipin antibody. Our case is the second reported associating APS with apoplexy. We discuss the clinical, biological and radiological features observed in our case. We conclude that APS should be searched for whenever a history of adenoma with apoplexy is found associated with recurrent thrombosis.


Collagen fibril diameter in relation to bone site. a quantitative ultrastructural study.
The collagen fibril diameter was measured in cortical bone samples from the femoral neck, rear and front tibia of rats using electron microscopy analysis. Statistically significant differences (0.001<p<0.04) in mean fibril diameter values between different bone sites were detected demonstrating a dependence upon bone use.


Retracted: Digital Transformation and Firm Performance in the Context of Sustainability: Mediating Effects Based on Behavioral Integration.
[This retracts the article DOI: 10.1155/2022/8220940.].


The specificity of integrin-ligand interactions in cultured human renal epithelium.
Members of the beta 1 integrin family are present at the basolateral membrane of human renal tubular epithelium in vivo and at the ventral surfaces of cultured renal epithelial cells, at the sites appropriate for cell substratum adhesion. In this study we have proven that these molecules are indeed functional in mediating cell substratum attachment in normal human renal epithelium by using monoclonal antibodies to integrin alpha subunits to block initial cell attachment. The importance of arginine-glycine-aspartic acid (RGD) recognition by cell surface receptors in various extracellular ligands was also examined using synthetic peptides. RGDS peptide strongly inhibited attachment to plain plastic or fibronectin-coated substrata but had no effect on cell adhesion to laminin-coated coverslips.


Unnecessary harm is avoided by reliable paediatric index of mortality2 scores without arterial gas sampling.
To investigate whether unnecessary harm could be avoided in children admitted to paediatric intensive care (PICU), we analysed the impact of arterial blood gas on the paediatric index of mortality score2 (PIM2) and the derived predicted death rate (PDR). From January 1, 2008 to December 31, 2010, 1793 consecutive admissions, newborn infants to 16 years of age (median 0.71 years) from a single, tertiary PICU in Gothenburg Sweden, were collected. Admission information on arterial oxygen tension (PaO2 ) and fraction of inspired oxygen (FiO2 ) was extracted from 990 admissions. There was close agreement between PIM2 score and PDR regardless of whether the PaO2 /FiO2 ratio was omitted or not. In the subgroup of admissions with a respiratory admission diagnosis, the inclusion of the PaO2 /FiO2 ratio increased the accuracy of the PIM2 score as well as the PDR. The standard mortality ratio was slightly but not significantly overestimated by excluding the PaO2 /FiO2 ratio. To avoid unnecessary harm to children admitted to PICU, an arterial blood gas analysis should only be performed if clinically indicated or if the child has a respiratory admission diagnosis. Estimation of the PIM2 score and PDR will not be less accurate by this approach.


Label-free Quantitative Analysis of Changes in Broiler Liver Proteins under Heat Stress using SWATH-MS Technology.
High temperature is one of the key environmental stressors affecting broiler production efficiency and meat yield. Knowledge of broiler self-regulation mechanisms under heat stress is important for the modern scale of poultry breeding. In the present study, the SWATH strategy was employed to investigate the temporal response of the broiler liver to heat stress. A total of 4,271 proteins were identified and used to generate a reference library for SWATH analysis. During this analysis, 2,377 proteins were quantified, with a coefficient of variation ≤25% among technical and biological replicates. A total of 257 proteins showed differential expression between the control and heat stressed groups. Consistent results for 26 and 5 differential proteins were validated respectively by MRM and western blotting quantitative analyses. Bioinformatics analysis suggests that the up- and down-regulation of these proteins appear involved in the following three categories of cellular pathways and metabolisms: 1) inhibit the ERK signaling pathway; 2) affect broiler liver lipid and amino acid metabolism; 3) induce liver cell immune responses to adapt to the high temperatures and reduce mortality. The study reported here provides an insight into broiler self-regulation mechanisms and shed light on the improved broiler adaptability to high-temperature environments.


Expression of the aromatase cytochrome P450 encoding gene in cattle and sheep.
During this report the tissue-specific expression and promoter usage of the aromatase cytochrome P450 encoding gene, Cyp19, are compared between cattle and sheep. In addition, data will be presented on the identification of cis-acting regulatory sequences located in the bovine placenta-specific promoter 1.1. In cattle and sheep Cyp19 is mainly expressed in the foetal placental layer and ovarian granulosa cells but also in other organs as brain or testis. Differently spliced transcripts of Cyp19 which include an invariable coding region but a variable 5'-untranslated region could be detected in tissues of both species. However, in contrast to ovary and brain which express homologous transcript variants, different transcripts are present in placentae suggesting that also different placenta-specific promoter regions are active in cattle and sheep. The analysis of the chromatin structure of the main placental promoter 1.1 in different bovine tissues revealed that hypomethylation and the occurrence of DNaseI hypersensitive sites (HS) within this region are associated with promoter activity. Active regulatory elements were identified in reporter gene studies in JEG-3 choriocarcinoma cells. The co-localisation of an E-box element within one of the placenta-specific HS suggests that this element is important for Cyp19 expression in the bovine placenta.


Episodic Hypertension With an Adrenal Mass: A Red Herring.
A 66-year-old man with symptomatic hypertensive episodes was found to have a 9-mm adrenal mass and elevated metanephrine levels. He was scheduled for an adrenalectomy for suspected pheochromocytoma. Subsequent workup revealed a large bladder mass which was found to be a paraganglioma. There is no consensus on what should be considered the standard management of primary bladder paraganglioma, including surgical technique, assessment of malignancy, and appropriate follow-up, owing to the rarity of the diagnosis.


Cholecystokinin-33 is more effective than cholecystokinin-8 in inhibiting food intake and in stimulating the myenteric plexus and dorsal vagal complex.
We compared the abilities of cholecystokinin-33 (CCK-33) and CCK-8 to reduce food intake and to activate feeding-related areas of the nervous system. (1) Overnight food-deprived rats were presented with a 10% sucrose solution, and intake was measured at 5-min intervals throughout a 90-min test beginning immediately after intraperitoneal injections of 1, 3, or 5 nMol/kg of CCK-33, CCK-8, or the vehicle control. In the initial 20 min (first meal), both peptides were equally effective, producing large reductions of food intake. Thereafter, however, CCK-33 was more effective than CCK-8, producing much more sustained reductions. Overall, both peptides reduced total food intake, but CCK-33 was more effective than CCK-8. (2) Possible roles for the myenteric plexus of the duodenum and the dorsal vagal complex (DVC) of the brainstem in the differential satiety effects of CCK-33 and CCK-8 were examined by quantifying CCK-33- and CCK-8-stimulated Fos-like immunoreactivity (Fos-LI) in each site. Consistent with the greater ability of CCK-33 to produce sustained inhibitions of food intake, CCK-33 produced more Fos-LI than CCK-8 in nearly every section of the sampled sites. The results demonstrate: (1) Different forms of CCK have different efficacies in reducing food intake; (2) CCK-33 produces a much more prolonged satiety action than CCK-8; and (3) the myenteric plexus and DVC may play roles in these differential satiety actions.


Correlation between conformation and antibody binding: NMR structure of cross-reactive peptides from T. cruzi, human and L. braziliensis.
The structure of peptides corresponding to the C-terminal residues from Trypanosoma cruzi (R13), human (H13) and Leishmania braziliensis (A13) ribosomal proteins were determined using nuclear magnetic resonance. Although there is only one amino acid difference between them, the peptides present distinct structures in solution: R13 adopts a random coil conformation while H13 and A13 form a bend. Interaction of these peptides with polyclonal antibodies from chronic Chagas' disease patients and a monoclonal antibody raised against T. cruzi ribosomal P2beta protein was probed by transferred NOE. The results show that the flexibility of R13 is fundamental for the binding to the antibody.


Three-dimensional sonographic description of the fetal frontal bones and metopic suture.
To describe the morphology of the frontal bones and metopic suture at 9-34 weeks of gestation using three-dimensional (3D) ultrasonography. This was a cross-sectional study of the frontal bones and metopic suture in 16 fetuses at 9-34 weeks of gestation. 3D ultrasonography was used to obtain volumes of the whole fetal skull in the mid-sagittal plane. The volumes were analyzed using the rendering mode and transparent maximum mode in order to achieve a clear view of the frontal bones and the metopic suture. At 9 weeks, a small ossification center was visible in the middle of each supraorbital part of the frontal bones and by 11 weeks the frontal bones appeared as 'thick eyebrows'. In the second trimester there was progressive radial bone expansion and delineation of the metopic suture and in the third trimester there was closure of the metopic suture, starting from the glabella and moving upwards towards the anterior fontanelle. This study provides 3D ultrasound images that illustrate the process of ossification of the frontal bones and the subsequent development of the metopic suture during prenatal life.


Predictors of Myocardial Dysfunction in Children with Indian Red Scorpion (Mesobuthus tamulus) Sting Envenomation.
To identify predictive risk factors for myocardial dysfunction in children with scorpion sting envenomation and to evaluate the effects of Scorpion antivenom and prazosin combination therapy on occurrence of myocardial dysfunction. Observational. Tertiary care hospital in Southern India. 85 children aged <13 years with scorpion sting envenomation. Frequency of myocardial dysfunction; predictors of myocardial dysfunction. 24 children (28.2%) developed myocardial dysfunction. Hypotension at admission (P=0.003) and increased time (>4h) between sting and administration of appropriate therapy (P=0.001) were independent predictors of myocardial dysfunction on logistic regression. Scorpion antivenom plus prazosin combination therapy led to an increase in cumulative proportion of children without myocardial dysfunction. Early (<4 hours) administration of Scorpion antivenom along with prazosin increases the cumulative percentage of children not developing myocardial dysfunction.


A common precursor to neurotensin and LANT6 and its differential processing in chicken tissues.
Antisera towards neurotensin (NT) and the structurally related peptide, LANT6, were used to characterize immunoreactive peptides and proteins in extracts of chicken tissues. A 17 kDa protein was identified by Western blotting as a potential precursor to NT and LANT6. However, the posttranslational processing of this common precursor appeared to be tissue specific, giving rise to disproportionate amounts of NT and LANT6, along with varying expression of a large molecular LANT6 (M(r), 15 kDa). The intestinal cells containing immunoreactive NT, LANT6, and large molecular LANT6 behaved similarly during fractionation by size and density. These activities also banded together in particles resembling vesicles during centrifugation of isotonic homogenates of tissue. These results suggest that chicken NT and LANT6 are biosynthesized as parts of the same precursor, the processing of which can give rise to a variety of products stored within secretory vesicles.


Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia.
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens and tissue injury. Defective apoptosis of activated immune cells leads to the development of autoantibodies in SLE. FasL initiated apoptosis is central for peripheral tolerance. Fas deficiencies in humans and mice predispose toward systemic autoimmunity. SLE is conferred by many genes. The genetic effects may be concentrated by familial clustering or by stratifying of subphenotypes. We have tested polymorphisms and haplotypes in FAS and FASL for association to SLE or subphenotypes in 126 multiplex American SLE pedigrees and found association of the FAS codon214 AC(C/T) as well as the FAS-670G>A'-codon214 AC(C/T)' haplotype to thrombocytopenia in SLE. Furthermore we have functionally characterized the FAS/FASL promoter polymorphisms associated with SLE in other populations and demonstrate that the activity depends on the allelic variants as well as on the haplotype. The presence of FAS-670G, which affects STAT1 binding, leads to the highest activity. FASL-844C activity is modified by the cis acting -478A and, hence, the haplotype and not the individual variant, determines the promoter activity. We conclude that the FAS/FASL promoter haplotypes are functional and that polymorphisms in FAS may contribute to thrombocytopenia in SLE.


Reinforcement context and resistance to change.
Eight pigeons responded in a multiple variable-interval (VI) schedule in which a constant component always delivered 40rft/h, and an alternated component was either rich (200rft/h) or lean (6.67rft/h) in different conditions. Four tests of resistance to change were conducted in each condition: prefeeding, full extinction, constant-component-only extinction, and response-independent food. Resistance to both prefeeding and full extinction in the constant component varied inversely with the reinforcement rate in the alternated component, but resistance to response-independent food did not. The extinction and response-independent food results were consistent with [J. Exp. Psychol.: Anim. Behav. Proc. 25 (1999) 256] behavioral momentum model. Maintaining reinforcement in the alternated component increased resistance to extinction in the constant component, as predicted by the behavioral momentum model but not accounts of multiple-schedule performance based on [J. Exp. Anal. Behav. 13 (1970) 243] equation. Overall, the momentum model gave a good account of the results with the exception of the prefeeding data. Possible ways to reconcile the prefeeding results with behavioral momentum theory are considered.


Phylogeny of trichostome ciliates (Ciliophora, Litostomatea) endosymbiotic in the Yakut horse (Equus caballus).
Ciliates of the subclass Trichostomatia inhabit the fermentative regions of the digestive tract of herbivores. Most available small subunit ribosomal RNA (SSrRNA) gene sequences of trichostomes are from species isolated from the rumen of cattle or sheep and from marsupials. No ciliate species endosymbiotic in horses has yet been analyzed. We have sequenced the SSrRNA genes of five ciliate species, isolated from the cecum and colon of four Yakut horses: Cycloposthium edentatum, Cycloposthium ishikawai, Tripalmaria dogieli, Cochliatoxum periachtum, and Paraisotricha colpoidea. Based on their morphology, Cycloposthium, Tripalmaria, and Cochliatoxum are classified as Entodiniomorphida, while Paraisotricha is considered a member of the Vestibuliferida. Phylogenetic analyses using Bayesian inference, distance, and parsimony methods confirm these placements. The two Cycloposthium species cluster together with the published Cycloposthium species isolated from a wallaby in Australia. Tripalmaria and Cochliatoxum branch as a sister group to or basal within the Entodiniomorphida. The Vestibuliferida remain paraphyletic with Paraisotricha and Balantidium branching basal to all other trichostome species, but not closely related to Isotricha and Dasytricha.


Transition of Care and Health-Related Outcomes in Pediatric-Onset Systemic Lupus Erythematosus.
Transition from pediatric to adult care is a complex process and can negatively impact patients with chronic disease. We describe the transition experience of patients with pediatric-onset systemic lupus erythematosus (SLE) and its associated outcomes in adulthood. A telephone survey of 41 pediatric-onset SLE patients was conducted following their transition to adult care. Data on medical and social outcomes during and after the transition were collected. Health status was compared to retrospectively collected baseline data at pediatric discharge. The mean ± SD followup interval was 5 ± 3.7 years; the mean ± SD age at followup was 24 ± 4.2 years. More than half of patients (22 of 41) experienced transition difficulties, primarily due to loss of insurance and emotional readjustment, which were associated with poor symptom control (P = 0.03) and multiple organ system involvement (P = 0.05) at followup. After the transition, most patients (35 of 41) were followed by an adult-care rheumatologist, and the majority (37 of 41) reported recent symptoms of active disease; 41% (13 of 29) had developed symptoms suggestive of new renal manifestations following transition. One-third (15 of 41) reported new or ongoing neuropsychiatric symptoms. Both renal and neuropsychiatric manifestations were associated with unemployment (P < 0.05). Direct referral by a pediatric rheumatologist was associated with fewer hospitalizations following transition (P = 0.04). The majority of patients transitioned successfully to adult rheumatologic care. Major challenges were loss of insurance and attachment to pediatric providers, highlighting the importance of a structured transition process that focuses on providing emotional and financial guidance. Disease activity in pediatric-onset SLE remains high throughout adulthood, with morbidity primarily related to renal and neuropsychiatric manifestations.


[Relative size of collagen body-peptides of the human cornea in the normal state and in keratoconus].
Recombination-kinetic study was carried out of the ratio between collagen secondary structures in human eye cornea of different age in the norm and in keratoconus. It has been shown that in both normal and pathologically changed cornea the portion of peptide chain in telopeptides is not changed within the age interval studied.


Bioinspired Reversible Switch between Underwater Superoleophobicity/Superaerophobicity and Oleophilicity/Aerophilicity and Improved Antireflective Property on the Nanosecond Laser-Ablated Superhydrophobic Titanium Surfaces.
In this work, the bioinspired reversible switch between underwater superoleophobicity/superaerophobicity and oleophilicity/aerophilicity and improved antireflective property were successfully demonstrated on the nanosecond laser-structured titanium surfaces. Titanium materials were first transformed to be superhydrophobic after nanosecond laser ablation and low-temperature annealing treatments, showing oleophilicity/aerophilicity in water. If the surfaces were prewetted with absolute ethanol and then immersed into water, the surfaces showed superoleophobicity/superaerophobicity. More importantly, the underwater oleophilicity/aerophilicity of the surfaces could be easily recovered by natural drying, and the switch between the underwater superoleophobicity/superaerophobicity and oleophilicity/aerophilicity could be repeated many cycles. Moreover, based on the original antireflective performance of the surface of the laser-ablated micro/nanoscale structures, we demonstrated that the inspired improved antireflective property could be skillfully realized by the prewetting treatment. The developed bioinspired multifunctional materials provide a versatile platform for the potential applications, such as controlling oil droplets, bubbles, and optical behavior.


Nonsteady motion in unloaded contractions of single frog cardiac cells.
We studied the mode of shortening of enzymatically isolated single frog cardiac cells with a high-speed videosystem to see whether or not shortening is smooth. The segmental shortening of the cell in response to electrical stimulation exhibited a clear pause following the initial shortening over a distance of approximately 11 nm/half-sarcomere. Several preparations showed a second pause following the initial one. Nonsteady motion with a pause lasted usually a few tens of milliseconds. The duration of nonsteady motion was shorter in cells with large velocities of steady shortening following the pause than those with smaller velocities.


Reduced ipsilateral hemispheric cerebral blood flow at admission is predictive of vasospasm with infarction after aneurysmal subarachnoid hemorrhage.
Cerebral vasospasm (CV) with infarction causes a significant degree of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). We sought to determine if reduced cerebral blood flow (CBF) on Xenon CT within 48 h of the ictus was predictive of developing CV with infarction. This is a prospective study from 1999 to 2006 of 97 patients with aSAH who underwent Xenon CT within 48 h of their bleed. Demographic, clinical, radiographic, and angiographic parameters were investigated as potential risk factors for the development of CV with infarction. A binary logistic regression analysis was performed to determine the independent predictors of this endpoint. A total of 97 patients with a mean age of 54 +/- 12 years were studied. A total of 78 (80.4%) patients presented with a Fisher grade of 3 and 51 (52.6%) patients with a Hunt Hess score >or=3. CV with infarction was found in 33 (34%) patients. In univariate modeling, younger patients with a Fisher scale of 3 or a reduced ipsilateral mean hemispheric CBF had an association with developing CV with infarction. In binary logistic regression modeling, patients with lower initial hemispheric CBF's were at a significant risk of CV with infarction in the ipsilateral hemisphere. Lower initial CBF at presentation is a risk factor for developing CV with infarction. These findings may help in early prediction of this entity and may have therapeutic implications in the future.


Deficits in visual function after resolution of optic neuritis.
A study was done to systematically characterize visual function in eyes with recovered optic neuritis. Thirty-five eyes from 27 patients, all of whom had recovered at least 20/30 Snellen acuity after resolution of the neuritis, were included. Minimum recovery period was 6 months. Abnormalities were found in color vision (57%), contrast sensitivity (72%), perimetry (26%), stereoacuity (80%), light brightness (89%), pupillary reaction (89%), and optic disc appearance (77%). Eighty-five percent of patients complained of at least some subjective disturbance in vision. Subjective visual complaints correlated better with deficits in contrast sensitivity than they did with the other measures. The results of the study indicate that deficits in visual function are common after resolution of optic neuritis.


Contrast-enhanced power Doppler sonography of malignant ovarian tumors using harmonic flash-echo imaging: preliminary experience.
To investigate the potential usefulness of contrast-enhanced intermittent harmonic sonography in the diagnosis of ovarian cancer, we evaluated 4 patients with complex adnexal masses suspected of malignancy using intermittent harmonic sonography after injection of a contrast agent. Tumor and/or mural nodule tissue enhancement was detected in all cases of ovarian malignancy. Contrast-enhanced, intermittent harmonic sonography provides a satisfactory visualization of blood flow in the solid portion of the tumor tissue and may support a diagnosis of ovarian malignancy. Depiction of blood vessels using low MI techniques may be possible with other vascular ultrasonographic contrast agents.


The importance of surgery and accurate axillary staging for survival in breast cancer.
The purpose of this study was to investigate, within the context of the Danish Breast Cancer Cooperative Group (DBCG) programmes, whether a dedicated surgical approach had a significant bearing on the outcome of breast cancer treatment. From 1 January 1980 to 31 December 1990, patients below 70 years of age with operable breast cancer from Odense University Hospital (n=743) were compared with those from the rest of Denmark (denoted rest-DK) (n=15,419). All patients were treated according to nationwide DBCG guidelines and reported to the DBCG Data Centre. The potential median observation time was 11.2 years (range 6.0-16.9). Patients underwent mastectomy or breast conserving therapy, and high risk lymph-node positive patients had adjuvant systemic therapy with or without radiotherapy. Comparing total patients series, overall survival (OS) was significantly superior in patients from Odense compared with rest-DK (P=0.02), with 10-year OSs of 62% (95% CI: 58-65%) and 56% (55-57%), respectively. In subgroups, the OS of low-risk node negative patients (protocol A) in Odense compared with rest-DK was significantly better (P=0.02); 10-year OS was 78% (73-84%) versus 72% (70-73%). Among the high-risk pre-menopausal patients (protocol B), the OS was significantly better in Odense (P=0.009); 10-year OS was 67% (60-75%) versus 53% (51-55%) in rest-DK. Post-menopausal high-risk patients (protocol C) did not differ significantly in OS between Odense and rest-DK (P=0.61). Locoregional control in the Odense series was superior compared with rest-DK. More lymph nodes were recovered and examined from the axilla in the Odense series than in rest-DK, a median of 10 vs. 6 nodes. In the Odense series, a significantly higher proportion of pre-menopausal patients had positive lymph nodes, predominantly one to three positive nodes, and subsequently a lower proportion of pre-menopausal patients had negative lymph nodes compared with rest-DK (P=0.02), indicating a more accurate staging in Odense vs. rest-DK. The survival benefit among the patients from Odense cannot be explained by stage migration alone, but seems to represent a true survival advantage. Overall mortality was significantly lower in the Odense series compared with rest-DK. Whether or not this difference could be explained by lower background mortality in the Odense series or was caused by superior treatment is discussed. The extent of surgery seems important for locoregional tumour control and accurate axillary lymph-node staging. In combination, these might lead to superior recurrence-free and overall survival, although differences in background mortality cannot be ignored. Surgery, therefore, might represent a risk factor by itself.


Total Synthesis and Structure Revision of Halioxepine.
The first total synthesis of halioxepine is accomplished using a 1,4-addition for constructing the quaternary center at C10 and a halo etherification for the generation of the tertiary ether at C7. The correct structure of halioxepine was determined by assembling different enantiomeric building blocks and by changing the relative configuration between C10 and C15.


EGFR Regulates the Hippo pathway by promoting the tyrosine phosphorylation of MOB1.
The Hippo pathway is frequently dysregulated in cancer, leading to the unrestrained activity of its downstream targets, YAP/TAZ, and aberrant tumor growth. However, the precise mechanisms leading to YAP/TAZ activation in most cancers is still poorly understood. Analysis of large tissue collections revealed YAP activation in most head and neck squamous cell carcinoma (HNSCC), but only 29.8% of HNSCC cases present genetic alterations in the FAT1 tumor suppressor gene that may underlie persistent YAP signaling. EGFR is overexpressed in HNSCC and many other cancers, but whether EGFR controls YAP activation is still poorly understood. Here, we discover that EGFR activates YAP/TAZ in HNSCC cells, but independently of its typical signaling targets, including PI3K. Mechanistically, we find that EGFR promotes the phosphorylation of MOB1, a core Hippo pathway component, and the inactivation of LATS1/2 independently of MST1/2. Transcriptomic analysis reveals that erlotinib, a clinical EGFR inhibitor, inactivates YAP/TAZ. Remarkably, loss of LATS1/2, resulting in aberrant YAP/TAZ activity, confers erlotinib resistance on HNSCC and lung cancer cells. Our findings suggest that EGFR-YAP/TAZ signaling plays a growth-promoting role in cancers harboring EGFR alterations, and that inhibition of YAP/TAZ in combination with EGFR might be beneficial to prevent treatment resistance and cancer recurrence.


Production optimization of invertase by Lactobacillus brevis Mm-6 and its immobilization on alginate beads.
A sequential optimization strategy, based on statistical experimental designs, was employed to enhance the production of invertase by Lactobacillus brevis Mm-6 isolated from breast milk. First, a 2-level Plackett-Burman design was applied to screen the bioprocess parameters that significantly influence the invertase production. The second optimization step was performed using fractional factorial design in order to optimize the amounts of variables have the highest positive significant effect on the invertase production. A maximal enzyme activity of 1399U/ml was more than five folds the activity obtained using the basal medium. Invertase was immobilized onto grafted alginate beads to improve the enzyme's stability. Immobilization process increased the operational temperature from 30 to 60°C compared to the free enzyme. The reusability test proved the durability of the grafted alginate beads for 15 cycles with retention of 100% of the immobilized enzyme activity to be more convenient for industrial uses.


On optimal control policy for probabilistic Boolean network: a state reduction approach.
Probabilistic Boolean Network (PBN) is a popular model for studying genetic regulatory networks. An important and practical problem is to find the optimal control policy for a PBN so as to avoid the network from entering into undesirable states. A number of research works have been done by using dynamic programming-based (DP) method. However, due to the high computational complexity of PBNs, DP method is computationally inefficient for a large size network. Therefore it is natural to seek for approximation methods. Inspired by the state reduction strategies, we consider using dynamic programming in conjunction with state reduction approach to reduce the computational cost of the DP method. Numerical examples are given to demonstrate both the effectiveness and the efficiency of our proposed method. Finding the optimal control policy for PBNs is meaningful. The proposed problem has been shown to be ∑2p - hard. By taking state reduction approach into consideration, the proposed method can speed up the computational time in applying dynamic programming-based algorithm. In particular, the proposed method is effective for larger size networks.


Caring for older patients with reduced decision-making capacity: a deductive exploratory study of ambulance clinicians' ethical competence.
As more people are living longer, they become frail and are affected by multi-morbidity, resulting in increased demands from the ambulance service. Being vulnerable, older patients may have reduced decision-making capacity, despite still wanting to be involved in decision-making about their care. Their needs may be complex and difficult to assess, and do not always correspond with ambulance assessment protocols. When needing an ambulance, older patients encounter ambulance clinicians who are under high workloads and primarily consider themselves as emergency medical care providers. This situates them in the struggle between differing expectations, and ethical conflicts may arise. To resolve these, providing ethical care, focussing on interpersonal relationships and using ethical competence is needed. However, it is not known whether ambulance clinicians possess the ethical competence required to provide ethical care. Thus, the aim of this study was to deductively explore their ethical competence when caring for older patients with reduced decision-making ability. A qualitative deductive and exploratory design was used to analyse dyadic interviews with ambulance clinicians. A literature review, defining ethical competence as comprising ethical sensitivity, ethical knowledge, ethical reflection, ethical decision-making, ethical action and ethical behaviour, was used as a structured categorization matrix for the analysis. Ambulance clinicians possess ethical competence in terms of their ethical knowledge, highlighting the need for establishing an interpersonal relationship with the older patients. To establish this, they use ethical sensitivity to interpret the patients' needs. Doing this, they are aware of their ethical behaviour, signifying how they must act respectfully and provide the necessary time for listening and interacting. Ambulance clinicians fail to see their gut feeling as a professional ethical competence, which might hinder them from reacting to unethical ways of working. Further, they lack ethical reflection regarding the benefits and disadvantages of paternalism, which reduces their ability to perform ethical decision-making. Moreover, their ethical knowledge is hampered by an ageist approach to older patients, which also has consequences for their ethical action. Finally, ambulance clinicians show deficiencies regarding their ethical reflections, as they reflect merely on their own actions, rather than on their values.


A quantitative measurement of spatial order in ventricular fibrillation.
The degree of organization in ventricular fibrillation (VF) is not known. As an objective measurement of spatial order, spatial correlation functions and their characteristic lengths were estimated from epicardial electrograms of pigs in VF. VF was induced by premature stimulation in five pigs. Electrograms were simultaneously recorded with a 22 x 23 array of unipolar electrodes spaced 1.12 mm apart. Data were obtained by sampling the signals at 2000 Hz for 20 minutes immediately after the initiation of FV. Correlations between all pairs of signals were computed at various times. Correlation lengths were estimated from the decay of average correlation as a function of electrode separation. The correlation length of the VF in pigs was found to be approximately 4 to 10 mm, varying as fibrillation progressed. The degree of correlation decreased in the first 4 seconds after fibrillation then increased over the next minute. The correlation length is much smaller than the scale of the heart, suggesting that many independent regions of activity exist on the epicardium at any one time. On the other hand, the correlation length is 4 to 10 times the interelectrode spacing, indicating that some coherence is present. These results imply that the heart behaves during VF as a high dimensional, but not random, system involving many spatial degrees of freedom, which may explain the lack of convergence of fractal dimension estimates reported in the literature. Changes in the correlation length also suggest that VF reorganizes slightly in the first minute after an initial breakdown in structure.


Circadian rhythm-modulated chemotherapy with high-dose 5-fluorouracil: a pilot study in patients with pancreatic adenocarcinoma.
From November 1986 to April 1989, 16 patients with advanced measurable pancreatic carcinoma were involved in a pilot phase I-II study. 5-Fluorouracil was given every 3 weeks by 5-day continuous chronomodulated venous infusion (CMVI) with peak 5-FU delivery at 4 a.m. Intrapatient dose escalation started at 1200 mg/m2/day up to 1600 mg/m2/day in the absence of grade III (WHO) toxicity. Mucositis and diarrhoea were dose limiting in the 131 cycles given. Three partial responses (21%) and 5 stable diseases were seen in the 14 patients with measurable disease. Dose intensity after three or after six courses (1800 mg/m2/week) was significantly correlated with time to progression (Pearson r = 0.64; P < 0.004). These results, although modest, support a multicentre phase II trial with 5-FU CMVI.


A phase III, multicenter, double-blind, randomized clinical trial to evaluate the efficacy and safety of ceftolozane/tazobactam plus metronidazole versus meropenem in Chinese participants with complicated intra-abdominal infections.
This study aimed to evaluate the efficacy and safety of ceftolozane/tazobactam (C/T) plus metronidazole versus meropenem plus placebo for the treatment of complicated intra-abdominal infection (cIAI) in Chinese adult participants. In this phase III clinical trial (NCT03830333), Chinese adult participants with cIAI were randomized 1:1 to receive C/T plus metronidazole or meropenem plus placebo. The primary objective was to assess C/T plus metronidazole for noninferiority versus meropenem for clinical response rate at the test of cure (TOC; 28 ± 2 days after study start) visit in the clinically evaluable population. Secondary endpoints included clinical and microbiologic responses at the TOC and end-of-treatment (≤24 hours after last dose) visits and adverse event rates. Clinical cure at the TOC visit in the clinically evaluable population was 95.2% and 93.1% for C/T plus metronidazole and meropenem, respectively (between-treatment difference: 2.1% [95% confidence interval: -4.7%, 8.8%]); thus, noninferiority was met. Clinical responses at the TOC and end-of-treatment visits and microbiologic responses at the TOC visit were consistent with the primary efficacy endpoint. Safety was comparable between study treatment groups. In Chinese adult participants with cIAI, C/T plus metronidazole was noninferior to meropenem, with comparable safety.


Environmental gradients of selection for an alpine-obligate bird, the white-tailed ptarmigan (Lagopus leucura).
The warming climate will expose alpine species adapted to a highly seasonal, harsh environment to novel environmental conditions. A species can shift their distribution, acclimate, or adapt in response to a new climate. Alpine species have little suitable habitat to shift their distribution, and the limits of acclimation will likely be tested by climate change in the long-term. Adaptive genetic variation may provide the raw material for species to adapt to this changing environment. Here, we use a genomic approach to describe adaptive divergence in an alpine-obligate species, the white-tailed ptarmigan (Lagopus leucura), a species distributed from Alaska to New Mexico, across an environmentally variable geographic range. Previous work has identified genetic structure and morphological, behavioral, and physiological differences across the species' range; however, those studies were unable to determine the degree to which adaptive divergence is correlated with local variation in environmental conditions. We used a genome-wide dataset generated from 95 white-tailed ptarmigan distributed throughout the species' range and genotype-environment association analyses to identify the genetic signature and environmental drivers of local adaptation. We detected associations between multiple environmental gradients and candidate adaptive loci, suggesting ptarmigan populations may be locally adapted to the plant community composition, elevation, local climate, and to the seasonality of the environment. Overall, our results suggest there may be groups within the species' range with genetic variation that could be essential for adapting to a changing climate and helpful in guiding conservation action.


Rapid microanalysis of coagulation parameters by automated chromogenic substrated methods - application in neonatal patients.
Daily monitoring of coagulation parameters in critically ill premature born neonates is only possible on small amounts of blood obtained by heelpuncture. Therefore, automated spectrophotometric micro-assays for antithrombin III (AT III), factors II and X, plasminogen and alpha 2 antiplasmin were applied on capillary and venous blood samples concurrently obtained in adults and healthy neonates. No statistically significant difference for any of the parameters was revealed. High levels of platelet factor 4 present in serial capillary samples of adults, did not interfere with the heparin dependent AT III assay. There was no evidence of thrombin or thromboplastin generation in these capillary samples, when examined for Va or VII activities. The levels of AT III, factors II and X and of plasminogen in neonates were 35-45% of the adult levels, in contrast to alpha 2 antiplasmin which was in the adult range.


Identification of a regulatory pathway of L-phenylalanine-induced GLP-1 secretion in the enteroendocrine L cells.
Glucagon like peptide-1 (GLP-1) is one of incretin hormone and is secreted when enteroendocrine L cells sense saccharides, amino acids, and fatty acids. Some amino acids have been shown to promote GLP-1 secretion from small intestinal enteroendocrine L cells. However, the molecular mechanisms that L-phenylalanine, a potent trigger of GLP-1 secretion, causes GLP-1 secretion from enteroendocrine L cells has not been elucidated. In this study, we used live-cell imaging to clarify the pathway by which L-phenylalanine activates enteroendocrine L cells. The results showed that L-phenylalanine was sensed by Gq-coupled receptor GPR142 and caused an increase in intracellular Ca2+ concentration. In addition, L-phenylalanine was taken up directly into the cell via Na+-dependent amino acid transporter, causing membrane depolarization and enhancing GLP-1 secretion. In summary, enteroendocrine L cells may regulate blood glucose levels in the body by detecting L-phenylalanine in the lumen and secreting GLP-1 via GPR142 and Na+-dependent amino acid transporters.


Bio-silica and bio-polyphosphate: applications in biomedicine (bone formation).
Bio-silica represents the main mineral component of the sponge skeletal elements (siliceous spicules), while bio-polyphosphate (bio-polyP), a multifunctional polymer existing in microorganisms and animals acts, among others, as reinforcement for pores in cell membranes. These natural inorganic bio-polymers, which can be readily prepared, either by recombinant enzymes (bio-silica and bio-polyP) or chemically (polyP), are promising materials/substances for the amelioration and/or treatment of human bone diseases and dysfunctions. It has been demonstrated that bio-silica causes in vitro a differential effect on the expression of the genes OPG and RANKL, encoding two mediators that control the tuned interaction of the anabolic (osteoblasts) and catabolic (osteoclasts) pathways in human bone cells. Since bio-silica and bio-polyP also induce the expression of the key mediator BMP2 which directs the differentiation of bone-forming progenitor cells to mature osteoblasts and in parallel inhibits the function of osteoclasts, they are promising candidates for treatment of osteoporosis.


Transvertebral anterior cervical foraminotomy: midterm outcomes of clinical and radiological assessments including the finite element method.
The aim of this study was to compare the clinical features, radiological changes, biomechanical effects, and efficacy in patients treated by transvertebral anterior foraminotomy. Preservation of segmental motion and avoidance of adjacent segment degeneration are theoretical advantages of transvertebral anterior foraminotomy. In practice, this procedure is minimally invasive and has shown good clinical results, especially in patients with unilateral cervical radiculopathy. We conducted a retrospective minimum 2-year follow-up study of the cervical spine of patients treated by transvertebral anterior foraminotomy at our institution. Radiological outcomes, which were estimated by measuring disc and functional spinal unit heights, and the angle and range of motion (ROM) from C2 to C7 of the functional spinal unit and adjacent segments were evaluated. Furthermore, a three-dimensional finite element method was used to biomechanically analyze the strength of the postoperative vertebral body. Between 2004 and 2009, 34 patients underwent surgery. The improvement rate was 94.2 %. The average flexion-extension ROM from C2 to C7 was 36.6 ± 16.6°. On plain radiographs, the disc height and ROM and height of the functional spinal unit in the operated segment were not significantly decreased relative to the preoperative levels. The finite element method also revealed that there was no difference in strength between the pre- and postvertebral bodies. These results demonstrate that biomechanical stability was achieved. Transvertebral anterior cervical foraminotomy did not limit motion in the operated and adjacent segments and did not cause a significant decrease in disc and vertebral heights after surgery.


Contextual emotion regulation therapy: a developmentally based intervention for pediatric depression.
For this special issue about child and adolescent depression, the authors were asked to describe contextual emotion regulation therapy as an example of a developmentally informed psychosocial intervention. The article begins with the authors' definition of the elements that should comprise such an intervention. A succinct summary of this contextual emotion regulation therapy is then provided, including its explanatory paradigm of depression, followed by an exposition of how it addresses the various definitional criteria of a developmentally informed intervention. The article concludes with a brief overview of the challenges of implementing a developmentally sensitive psychotherapy for depressed children and adolescents.


Suppression by dexamethasone of vascular permeability responses induced with leukotrienes C and D in the rat skin.
The present experiment was designed to investigate whether glucocorticoids counteract proinflammatory action of leukotrienes C and D which were suggested to play an important role as mediators in the inflammatory exudate response. Vascular permeability was measured using 131I-labeled human serum albumin (131I-HSA) as a tracer. The vascular permeability was elevated promptly after intradermal injection of chemically synthesized leukotriene C or D and then rapidly fell down to the control level. A positive dose-response relationship was observed in the dose levels of 0.01-1 microgram of leukotrienes. Dexamethasone at doses of 0.15, 0.5 and 1.5 mg/kg caused dose-dependent suppression of vascular permeability response induced with leukotrienes C and D. The present data indicate that glucocorticoids are capable of exerting direct inhibitory effect against proinflammatory action of leukotrienes C and D produced through phospholipase A2-arachidonate-lipoxygenase pathway.


Cell Division Control Protein 42 Facilitates Diabetic Retinopathy Progression by Activating the MEK/ERK Pathway.
Cell division control protein 42 (CDC42) modulates insulin secretion and angiogenesis to participate in the pathology of diabetic complications and retinal vascular-associated diseases. This study intended to explore the role of CDC42 in the progression of diabetic retinopathy, and the underlying mechanism. Human retinal microvascular endothelial cells (hRMECs) were cultured in 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose; HG) medium, respectively. CDC42 overexpression plasmid and small interference RNA (oe-CDC42 and si-CDC42) or corresponding negative controls (oe-NC and si-NC) were transfected into hRMECs under HG. Then, platelet-activating factor C-16 (C16-PAF) (MEK/ERK pathway activator) was added to si-CDC42 or si-NC transfected hRMECs under HG. Our study showed that HG increased CDC42 mRNA and protein, cell viability, invasive cell count, branch points, and tube length but reduced cell apoptosis in hRMECs. CDC42 upregulation enhanced cell viability, invasive cell count, branch points, tube length, p-MEK, and p-ERK, but attenuated cell apoptosis. Downregulation of CDC42 exhibited opposite trends. In addition, C16-PAF also increased cell viability, invasive cell count, branch points, and tube length, p-MEK, and p-ERK, but retarded cell apoptosis. Notably, C16-PAF diminished the effect of CDC42 downregulation on the above-mentioned functions in hRMECs under HG. Conclusively, CDC42 promotes HG-induced hRMEC viability and invasion, as well as angiogenesis, but inhibits apoptosis by activating the MEK/ERK pathway, which may be responsible for the progression of diabetic retinopathy.


Fatal Toxicity Indices for Medicine-Related Deaths in New Zealand, 2008-2013.
The fatal toxicity index (FTI) is a measure for assessing the relative risks of death due to the medicines prescribed in a population. This knowledge is useful for prescribers and informs medicine safety initiatives. This study aimed to calculate FTIs for the New Zealand population using three methodologies. New Zealand coronial data describing medicine-related deaths from 1 January 2008 to 31 December 2013 were retrospectively extracted from the National Coronial Information System. Three fatal toxicity indices were derived using the number of deaths attributed to each pharmaceutical as the numerator and the total defined daily doses, number of patients and number of prescriptions as denominators. There were 703 medicine-related deaths, of which 627 were assessed as due to one primary contributor. Median decedent age was 48 years (interquartile range 37-58), and 319 (51%) were male. Deaths were intentional in 252 cases (40%), unintentional in 284 (45%) and unknown in 91 (15%). The majority of deaths (n = 486, 78%) occurred in the community. Opioids, antidepressants, antipsychotics and hypnotic-anxiolytics caused most fatalities. While the FTIs for individual medicines varied by denominator applied, methadone and clozapine fatalities were prominent in all three indices. The antidepressants clomipramine, dosulepin and doxepin consistently returned the highest FTIs in their group. New Zealand prescribers should be aware of the high relative risk of death associated with methadone and clozapine; that clomipramine, dosulepin and doxepin were identified as the most dangerous antidepressants; and that zopiclone carries a similar fatal risk to benzodiazepines. Varying results were found between the FTIs calculated, making comparisons, particularly between populations, difficult.


Comparison of urinary human follicle-stimulating hormone and human menopausal gonadotropin for ovarian stimulation in polycystic ovarian syndrome.
A randomized, double-blind, crossover study was carried out to compare purified urinary follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) for ovarian stimulation in polycystic ovarian syndrome (PCOS). Twelve patients were stimulated with FSH and hMG in three alternate cycles. FSH, luteinizing hormone (LH), estradiol, dihydroepiandrosterone sulphate, free and total testosterone, delta 5-androstenedione, sex hormone binding globulin, and ovarian volume were monitored during the stimulation. There was no difference between the dose of FSH and hMG necessary to induce preovulatory follicles in the individual patients. The mean increase of ovarian volume during stimulation with FSH and hMG was 120% and 129% respectively (no significant difference). Two patients became pregnant in the first cycle. Two other patients had delayed bleeding and positive serum-human chorionic gonadotropin. No significant difference was found in the endocrine changes during the two different stimulation methods. The LH/FSH ratio was normalized after a few days of treatment regardless of the type of stimulation. The size of the material does not permit a comparison of the efficacy of the two treatment schedules. Our clinical and ultrasonic observations do not support the theory that treatment of infertility in PCOS with FSH is more safe than with hMG.


Analytical profiling and stability evaluation of liposomal drug delivery systems: A rapid UHPLC-CAD-based approach for phospholipids in research and quality control.
Phospholipids and their derivatives represent a broad range of multifunctional substances used as excipients or active ingredients by different industries due to their natural origin and unique properties. A fast and reliable quantification as well as comprehensive stability evaluation are of major importance in the process of development and quality control of lipid-based systems. Therefore, the present study is focused on the development and validation of a rapid ultra-high performance liquid chromatography - charged aerosol detector based (UHPLC-CAD) method for simultaneous detection of a multitude of natural and synthetic lipids, (charged) phospholipids, lipophilic fluorescent markers and their possible degradation products. Twenty-two compounds were characterized by a strong linear response of the detector (R2 > 0.97). Moreover, remarkable limits of detection (≤10 μg mL-1) and limits of quantification (≤25 μg mL-1) associated with a consistent reproducibility were achieved for all tested molecules. The performance of the analytical method was demonstrated by analyzing the lipid composition (after different production stages and photodegradation) of both bupivacaine loaded liposomes and a Doxil®-like formulation. The newly developed method combines a rapid, comprehensive, and efficient quantification with minimal economic effort and ecologic consequences, meeting the requirements of modern analytical processes and offering a broad range of possible applications in various industrial sectors and scientific laboratories.


Atherogenic diets and neutral-lipid organization in plasma low density lipoproteins.
The plasma low density lipoproteins (LDL) of rhesus monkeys fed 3 atherogenic diets exhibited thermal transitions at temperatures much higher (37--43 degrees C) than those observed in control animals or in normal humans (20--33 degrees C). The same differences were noted in the neutral lipids (cholesteryl esters and triglycerides) which were isolated from the respective lipoproteins. In particular, the difference in thermal properties between the normal and abnormal LDLs was attributable to subtle differences in their cholesteryl ester compositions (mainly an increase in the saturated and monounsaturated fatty acid moieties), with altered triglyceride contents playing only a minor role. Thus, at body temperature, the hyperlipidemia that follows the administration of atherogenic diets is associated with a high degree of order of the neutral lipids in the core of the LDL particle. This, in turn, may be related to the atherogenicity of the abnormal lipoprotein species.


Elephant pituitary gonadotropins.
We describe for the first time the purification and some properties of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) isolated from anterior pituitary tissue of the African elephant (Loxodonta africana). Methodology previously applied to equine and donkey pituitaries was used to obtain purified preparations of elephant LH and FSH in yields of 8.8 and 0.48 mg, respectively, per 10 g pituitary powder. The preparations were characterized by HPLC gel filtration and amino acid analysis, both of which showed the elephant LH and FSH to be very similar to ovine LH and FSH. The preparations were also characterized by radioimmunoassays and bioassays for LH and FSH and a radioreceptor assay for FSH. Results showed virtually no cross-contamination of hormonal activities in the elephant LH and FSH preparations. Elephant LH potencies ranged from 50 to 66% of highly purified ovine LH and elephant FSH potencies ranged from 21 to 52% of highly purified ovine FSH in the various assays employed. No evidence was found for any demonstrable intrinsic FSH activity in elephant LH. The assays employed suggest possible usage for making physiological measurements of gonadotropins in the elephant.


Maxillofacial manifestations of Proteus syndrome: a systematic review with a case report.
Proteus syndrome (PS) is an extremely rare disorder with asymmetric and disproportionate bone overgrowth. Craniofacial abnormalities in PS are less frequent than skeletal abnormalities. Although there are recognized oral and maxillofacial manifestations of PS, few case reports describing these manifestations are available. Thus, the objective of this systematic review and case report is to describe oral and maxillofacial manifestations of PS and to report a PS case. A 31-year-old male presented with restricted mouth opening and pain during mastication. A panoramic radiograph and an occlusal radiograph were obtained. Reports with relevant keywords were assessed. Data were summarized and demonstrated using a critical appraisal checklist for case reports. The panoramic radiograph demonstrated unilateral overgrowth of the mandible, impacted teeth, and deciduous prolonged retention. Thirteen PS case reports were identified. Proteus syndrome oral and maxillofacial manifestations may include dental agenesis, impacted teeth, malocclusion, asymmetric dental growth and maturation, frontal line displacement, asymmetric tongue enlargement, mandibular hemihypertrophy and asymmetry, presence of exostoses/hyperostosis, degenerative changes in the temporomandibular joint, alterations of maxillary and mandibular vertical and/or horizontal growth, and enlargement of mandibular canal and foramen. The PROSPERO systematic review registration number is CRD42019140942.


Hip fractures in young patients: is this early osteoporosis?
Hip fracture in patients under age 50 is rare, and is often not attributable solely to the energy of injury. Our aim was to determine if trabecular bone mineral density (BMD) is abnormal in young patients with hip fractures. We reviewed all hip fractures treated at our institution between 1979 and 1986 and contacted 20 patients under the age of 50 at the time of injury, all of whom wished to be studied. The mean age at the time of injury was 39 (range 24-47). Subjects were questioned for osteoporosis risk factors, classified by level of energy producing their injury, and then underwent quantitative computed tomography (QCT) bone densitometry of trabecular bone in the lumbar spine. Bone mineral density by QCT was below the mean for age in 90% of the patients, and was greater than 1 SD below the mean in 75%. Mean percentage BMD decrease from age-matched controls was 34% (P less than 0.005) in women and 19% (P less than 0.005) in men. There was an inverse correlation in the degree of BMD decrease and the energy level of injury. There was a direct correlation of the severity of BMD decrease and the cumulative number of osteoporosis risk factors. This investigation has found that 1-7 years following hip fracture, otherwise presumedly healthy young patients demonstrate a statistically significant decrease in spinal BMD from age/sex-matched controls. These data do not determine if osteopenia is the cause or the result of injury, nor do we wish to infer that measurement of bone density at one site can predict future fractures at other sites.(ABSTRACT TRUNCATED AT 250 WORDS)


Oropharyngeal cancer pathogenesis: ubiquitin proteolytic, apoptotic and epidermal growth factor related pathways act in concert--first report.
The current study was carried out to examine the clinical characteristics and survival-probability rates of 51 patients treated for oral (tongue) cancer and to correlate it with various tumor markers. The clinical data and survival probability rates were correlated with the immunohistological analysis of p27, Skp2, p53, Bcl-2, TUNEL (apoptotic rate) and c-erbB-2 markers. The 5-year survival-probability correlated with staging, grading and base of tongue location. An inverse relation between the expression of p27 and Skp2, p27 and grading, and a direct relation between Skp2 and grading were demonstrated. Concomitantly, significant correlations between low p27, high Skp2 and high TUNEL (apoptotic rate) expressions and between low p27 and high c-erbB-2 (Her2) expressions in the cancer lesions were demonstrated. The accumulated data may be employed in the future for a better understanding of the biology behind oral cancer and for developing better means of detection and treatment.


Electric scooter sharing systems: An analysis of injury patterns associated with their introduction.
With the increasing popularity of electric scooters (ES) and the introduction of ES sharing systems in 2017, hospitals are seeing more ES-related injuries. The effects of sharing systems on traumatic injuries are lacking in the literature. We, therefore, sought to describe trends in ES injuries. The Nationwide Inpatient Sample was queried for patients hospitalized with ES-related injuries in the United States from 2015 to 2019. Admissions due to ES were divided into two cohorts: before (≤2017) and after (>2018) the introduction of sharing systems. Patients were stratified by injuries sustained, age, gender, and race. Inpatient hospital charges and length of stay were compared. Exclusion criteria included patients older than 65 and patients with neurological disorders. Traumatic injuries were compared after adjusting for age, gender, and race in a multivariate logistic regression analysis. During the study period, there were 686 admissions, of which 220 remained due to exclusion criteria. There was a consistent increase in ES-related injuries over the years (r = 0.91, p = 0.017). Patients who were injured after the introduction of sharing systems were more likely to sustain facial fractures (OR, 2.63; 95%CI, 1.30-5.32; p = 0.007) after controlling for age, gender, and race. The incidence of lumbar and pelvic fractures was higher following the introduction of such systems (7.1% vs. 0%; p<0.05). The introduction of ES sharing systems resulted in increased incidence of facial, pelvic, and lumbar fractures. Federal and state regulations need to be implemented to mitigate the detrimental effects of ES sharing systems.


[Surgical tactics and results of the treatment of penetrating wounds of the eye with foreign bodies in the posterior segment].
Analyzes 147 cases with perforating wounds of the eyes and foreign bodies in the posterior segment. Describes the surgical policy in removing the foreign bodies in cases with transparent and opaque refracting madia. Recommends the transciliary methods providing better functional results.