[Multiple sclerosis: review of main experimental data and pathogenic hypotheses].
The pathogenesis of multiple sclerosis (MS) is considered from three different viewpoints: genetic, viral and immunological. A genetic predisposition intervenes, as testified by the familial forms of MS and by the frequency of HLA A3B7 and DR2 groups in MS patients. The hypothesis of an inherited enzyme deficiency in oligodendrocytes is discussed. Many viruses are known to induce demyelination in animals, and the intrathecal production of antibodies to measles virus as well as the in vitro discovery of DNA transcripts of this virus in patients are suggestive of a viral factor. Experimental allergic encephalomyelitis (EAE) and chronic EAE have made it possible to study the immune and other mechanisms which might be involved in MS. While the myelin basic protein and the M2 antigen appear to be the first antigen targets, the demyelinating agents in this model are antibodies to galactocerebroside. The factors responsible for demyelination in MS have not yet been elucidated, but the antibodies present in the cerebrospinal fluid do not seem to be demyelinating in vitro. Descriptions of the cells which constitute the lesions and of the antigen markers they express suggest that endothelial cells and astrocytes (possibly presenting antigens to lymphocytes) might play a part in the genesis of the lesions. Experiments concerning the modulation and suppression of EAE allow new therapeutic approaches to be envisaged.


Comparison of stress levels among medical and dental students in the clinical years of training and their coping strategies.
To compare the stress levels among medical and dental students and to evaluate their coping strategies. The cross-sectional comparative study was conducted at the Liaquat College of Medicine and Dentistry, Karachi, from January to February 2018, and comprised medical students from 3rd, 4th and 5th years, and dental students of 3rd and 4th year. Cohen Perceived Stress Scale was used to collect data which was then analysed using SPSS 21. Of the 400 students approached, 281(70.25%) responded. There were 159(56.5%) medical and 122(43.4%) dental students. Also, 78(27.7%) students were males and 203(72.2%) were females. The stress level was moderate or high in 267(95%) students; 118(96.7%) dental, 149(93.7%) medical. Stress management strategies included meditation/praying 181(64.4%), spending some time to relax 180(64.1%) and sleeping 177(63%). Dental students had slightly higher stress level than medical students. The most common stress management strategy was meditation/praying.


The Fruit Fly Drosophila melanogaster as a Model for Aging Research.
: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.


A multi-level bioreactor to remove organic matter and metals, together with its associated bacterial diversity.
The purpose of this study was to treat complex wastewater consisting of domestic wastewater, tobacco processing and building materials washings. The proposed multi-level bioreactor consists of a biopond-biofilter, anoxic/aerobic (A/O) fluidized beds and a photoautotrophic system. The results show that when the hydraulic load of the bioreactor was 200 m3/d, it successfully and simultaneously removed the organic matter and metals. When the bioreactor was in a relatively steady-state condition, the overall average organic matter and metals removal efficiencies are as follows, COD (89%), UV245 nm-matter (91%), Cu (78%), Zn (79%) and Fe (84%). The growth conditions of the native bacterial habitat were improved, which resulted from the increase of the in bacterial diversity under the rejuvenated conditions induced by the bioreactor. The results demonstrate that the multi-level bioreactor, without a sludge treatment system, can remove heterogeneous organic matter and metals from wastewater.


An extremely rare case report of surgery of lung cancer with the absence of azygos vein.
In thoracic surgery, we occasionally encounter vessel anomalies. We herein report an extremely rare surgical case with the absence of the azygos vein. Mediastinal vascular abnormalities are said to be rare. The etiology of vascular abnormalities of the whole body, including the chest is known gene mutations, hormone abnormalities, infection, and trauma. But, many causes have been unknown. In thoracic surgery field, there is some reports and literature about pulmonary arteriovenous malformation, pulmonary sequestration, and partial anomalous pulmonary venous return. But reports about absence of azygos vein are not much. It is considered that it is less likely to become a problem in clinical. As we discussed in the paper, it will be more interesting if the association with PLSVC reveals from more cases. A 58-year-old man was admitted to our hospital in order to undergo operation for the treatment of lung cancer. We detected absence of the azygos vein by preoperative computed tomography (CT). Furthermore, three-dimensional angiography (3D-angiography) showed that the right superior intercostal vein and hemiazygos vein in the left thoracic cavity were more developed than usual. Then, we discuss the key points during surgery and suggest the potential association between the absence of the azygos vein and a persistent left superior vena cava (PLSVC).


The effect of refractive error on optokinetic nystagmus.
Subjective refraction is the gold-standard for prescribing refractive correction, but its accuracy is limited by patient's subjective judgment about their clarity of vision. We asked if an involuntary eye movement, optokinetic nystagmus (OKN), could serve as an objective measure of visual-clarity, specifically measuring the dependence of OKN-elicited by drifting spatial-frequency filtered noise-on mean spherical equivalent (MSE) refractive error. In Experiment 1 we quantified OKN score-a measure of consistency with stimulus-direction-for participants with different MSEs. Estimates of MSE based on OKN scores correlate well with estimates of MSE made using autorefraction (r = 0.878, p < 0.001, Bland-Altman analysis: mean difference of 0.00D (95% limits of agreement: - 0.85 to + 0.85D). In Experiment 2, we quantified the relationship between OKN gain (ratio of tracking eye-movement velocity to stimulus velocity) and MSEs (- 2.00, - 1.00, - 0.50, 0.00 and + 1.00D) induced with contact lenses for each participant. The mean difference between measures of MSE based on autorefraction or on OKN gain was + 0.05D (- 0.90 to + 1.01D), and the correlation of these measures across participants was r = 0.976, p < 0.001. Results indicate that MSE attenuates OKN gain so that OKN can be used as an objective proxy for patient response to select the best corrective lens.


Prognostic value of indoleamine 2,3-dioxygenase activity and expression in nasopharyngeal carcinoma.
Indoleamine 2,3-dioxygenase (IDO) is an enzyme with an immunosuppressive effect whose function is diverted by tumor cells to counteract immune cell functions, inducing immune escape of tumor cells. The aim of this study was to investigate the clinical significance of IDO in nasopharyngeal carcinoma (NPC). Compared to controls, NPC patients' plasma IDO activity was significantly higher, especially among patients with metastatic cancer (p=0.005). The immunohistochemical analysis revealed that high IDO expression was observed in 74% of NPC tissues and the epithelial IDO expression was inversely correlated to T-cell infiltration. Kaplan-Meier survival analysis showed that whatever the localization, intratumoral or stromal, patients with a high IDO expression and low T-cell infiltration have significantly lower survival rates. Moreover, in multivariate analysis, intratumoral and stromal IDO expression were found to be independent prognostic factors for disease-free survival (p=0.016; HR: 3.52) and overall survival (p=0.015; HR: 4.76) respectively. Our findings provide evidence that IDO is involved in tumor immune evasion of NPC, suggesting that it could be a relevant therapeutic target for NPC.


'Windows of opportunity': exploring the relationship between social media and plastic policies during the COVID-19 Pandemic.
Plastic pollution has reached a crisis point due to ineffective waste management, an over-reliance on single-use plastic items and a lack of suitable plastic alternatives. The COVID-19 Pandemic has seen a dramatic increase in the use of single-use plastics including 'COVID waste' in the form of items specifically intended to help stop the spread of disease. Many governments have utilised COVID-19 as a window of opportunity to reverse, postpone or remove plastic policies off agendas ostensibly in order to 'flatten the curve' of COVID-19 cases. In this paper, we use novel methods of social media analysis relating to three regions (USA, Mexico and Australia) to suggest that health and hygiene were not the only reasons governments utilised this window of opportunity to change plastic policies. Beyond the influence of social media on the plastics agenda, our results highlight the potential of social media as a tool to analyse public reactions to government decisions that can be influenced by industry pressure and a broader political agenda, while not necessarily following responses to consumer behaviour.


Cost-effectiveness of EGCRISC application versus hepatitis C virus mass screening in Egypt.
The Egyptian model of care against hepatitis C virus (HCV) has a great success in treatment and treatment accessibility, but still screening efforts must be strengthened. HCV is a silent infection when most of infected people are unaware of their infection. EGCRISC is a newly developed and validated risk-based HCV screening tool in Egypt that has shown a considerably good performance but is still underused. This brief communication is to analyze its use cost-effectiveness versus mass screening. Mathematical comparative analysis for economic evaluation. Its performance data as published recently were used, and a minimum cost of L.E. 20 was considered per one antibody testing. The 2015 health issue survey and population census were used for estimating the population, infected individuals and susceptibles. The analysis showed that using EGCRISC would save LE 0.43 billion accounting for about 21,646,227 unnecessary tests, while missing less than 70,000 cases when compared to mass screening. EGCRISC is a cost-effective tool that must be adopted nationwide as soon as possible in Egypt for the best outcome of HCV control.


Group II spindle fibres and afferent control of stance. Clues from diabetic neuropathy.
Since patients with large-fibre neuropathy do not show abnormal body sway during stance, the hypothesis was tested that postural control is not impaired until myelinated fibres of medium size are affected. In 22 diabetic neuropathic patients and 13 normals, we recorded: (1) body sway area (SA), (2) stretch responses of soleus (Sol) and flexor digitorum brevis (FDB) to toe-up rotation of a platform, (3) Sol and FDB H reflex and FDB F wave, (4) conduction velocity (CV) of tibial, deep peroneal and sural nerve. In patients, detection thresholds for vibration, cooling (CDT), warming and heat-pain (HPDT) were assessed. Body SA was increased in patients with respect to normals. Toe-up rotation elicited short- (SLR) and medium-latency (MLR) responses in Sol and FDB in all normals. In patients, SLR was absent in FDB and reduced in Sol, and MLR was delayed in both muscles; the FDB H reflex was absent. The CV of tibial nerve group II afferent fibres, as estimated from the afferent time of FDB MLR, was reduced in patients. All sensory detection thresholds were increased. Stepwise multiple regression showed that increased SA was explained by increased latency of MLR, decreased CV of group II fibres and augmented CDT and HPDT. Unsteadiness in diabetic neuropathy is related to alterations in medium-size myelinated afferent fibres, possibly originating from spindle secondary terminations.


Local mobility of nucleic acids as determined from crystallographic data. III. A daunomycin-DNA complex.
The local mobility of the complex between the anti-tumor drug daunomycin and a DNA hexanucleotide duplex of sequence d(CpGpTpApCpG)2 has been determined by anisotropic refinement of single crystal X-ray diffraction data of 1.2 A resolution (1 A = 0.1 nm). The directions and amplitudes of the local motion indicate that changes in mobility of DNA due to daunomycin binding are primarily limited to the residues forming the intercalation site and do not propagate to the neighboring residues. The intercalated daunomycin ring system (aglycone) is rigidly fixed in the base stack, apparently serving as an anchor for the amino sugar segment of the drug which is one of the most mobile regions of the entire complex. The high flexibility of this amino sugar may be important for inhibition of replication and transcription not only by sterically blocking the minor groove, but also by allowing nonproductive interactions to be formed with various polymerases or other DNA-binding proteins. The crystallographic model is improved sufficiently by the rigid group anisotropic refinement to allow additional bound water molecules to be located.


[Increased mortality and disability in a cohort of Mexican children with maple syrup urine disease].
Maple syrup urine disease (MSUD) is a genetic disorder that produces ketoacidosis crises and neurological complications often leading to death. The age of diagnosis and treatment determine a child's adequate and healthy outcome. Describe the characteristics of a pediatric Mexican cohort with MSUD. Retrospective analysis of MSUD cases seen at our Metabolic Unit between 1991- 2006. We studied 36 patients; three were initially detected through neonatal screening, one of them done in Mexico and two in the United States. The latter were given timely treatment and developed normally, both intellectually and physically. The patient detected in Mexico was not given adequate treatment and died at 3 months of age. The remaining 33 patients were diagnosed between 2-24 months using standard biochemical tests performed after symptoms became noticeable. All symptomatic patients had high levels of branched-chain amino acids. Hypotonia, refusal to eat and seizures were the most frequent symptoms. The cohort's mortality was 50% (18/36), while 81.2% (13/18) of survivors displayed cognitive impairment. Mexico needs a comprehensive treatment protocol for the care of MSUD patients including newborn screening, early treatment, follow-up and genetic counseling.


Cbls boost B cells.
T cell regulation of antibody-mediated immunity is critical for health. In this issue of JEM, Li et al. (https://doi.org/10.1084/jem.20191537) identify the Cbl family of E3 ubiquitin ligases as B cell-intrinsic gatekeepers of T cell-dependent humoral immunity.


Regioselective monoacylation of 2-O-α-D-glucopyranosyl-L-ascorbic acid by a polymer catalyst in N,N-dimethylformamide.
6-O-Dodecanoyl-2-O-α-D-glucopyranosyl-L-ascorbic acid (6-sDode-AA-2G) was synthesized from 2-O-α-D-glucopyranosyl-L-ascorbic acid and lauric anhydride with a polymer catalyst, poly(4-vinylpyridine), in N,N-dimethylformamide without the introduction of protecting groups. The optimum reaction conditions enabled 6-sDode-AA-2G to be synthesized in a yield of 49.7%. The yield and the regioselectivity in this method were far superior to those in our previous method by using an enzyme. The polymer catalyst could be recycled more than five times without any significant activity loss.


Cave-dwelling flies in Central Europe: adaptation to environment, especially to low temperatures (Diptera, Nematocera: Trichoceridae et Sciaridae).
For Trichocera maculipennis Meig. and Trichocera regelationis (L.) (Diptera, Nematocera: Trichoceridae), and for Bradysia forficulata (Bezzi) (Diptera, Nematocera: Sciaridae), the total length of development (duration of one generation), and of pupal development alone, plotted against temperature, are described by hyperbolic equations. The derived lower limits (zero points) for total development are-1.5° C for T. maculipennis,-2.9° C for T. regelationis and-0.3° C for B. forficulata. The corresponding points for pupal development are-3.6° C,-2.5° C and +0.5° C. At least for several single stages development is proved to occur at temperatures slightly below zero for both Trichocera species. Furthermore the upper limits for development are reached at relatively low temperatures: +18° C for T. maculipennis, between +16 and +17° C for T. regelationis and +20° C to +22° C for B. forficulata. B. forficulata inhabits caves exclusively, while the Trichocera species are wide spread field species, especially in northern Europe. The similarity of all characteristics of development investigated in all three species suggests that the field populations of Trichocera are very well "preadapted" to life in Central European carstic caves.


Could a man be affected with carcinoma of cervix?--The first case of cervical carcinoma in trans-sexual person (FtM)--case report.
The article presents an unique case of trans-sexual person (FtM) with histological finding of pre-invasive cervical carcinoma after performed hysterectomy.


Generation and immunogenicity of porcine circovirus type 2 chimeric virus-like particles displaying porcine reproductive and respiratory syndrome virus GP5 epitope B.
Virus-like particles (VLPs) can be used as transfer vehicles carrying foreign proteins or antigen epitopes to produce chimeric VLPs for bivalent or multivalent vaccines. Based on the crystal structure of porcine circovirus type 2 (PCV2) capsid protein (Cap), in addition to alignment of the Cap sequences collected from various isolates of PCV2 and PCV1, we predicted that Loop CD of the PCV2 Cap should tolerate insertion of foreign epitopes, and furthermore that such an insertion could be presented on the surface of PCV2 VLPs. To validate this, the GP5 epitope B of porcine reproductive and respiratory syndrome virus (PRRSV) was inserted into Loop CD of the PCV2 Cap. The 3D structure of the recombinant PCV2 Cap (rCap) was simulated by homology modeling; it appeared that the GP5 epitope B was folded as a relatively independent unit, separated from the PCV2 Cap backbone. Furthermore, based on transmission electron microscopy, the purified PCV2 rCap self-assembled into chimeric VLPs which entered PK-15 cells. In addition, PCV2 chimeric VLPs induced strong humoral (neutralizing antibodies against PCV2 and PRRSV) and cellular immune responses in mice. We concluded that the identified insertion site in the PCV2 Cap had great potential to develop PCV2 VLPs-based bivalent or multivalent vaccines; furthermore, it would also facilitate development of a nano-device to present a functional peptide on the surface of the VLPs that could be used for therapeutic purposes.


TFE3 Gene Rearrangement in Perivascular Epithelioid Cell Neoplasm (PEComa) of the Genitourinary Tract.
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms with unpredictable behavior. They are characterized by epithelioid cells, which stain with melanocytic markers, associated with spindle cells reactive for smooth muscle markers. PEComas may be sporadic or associated with the tuberous sclerosis complex, with mutations affecting mostly tuberous sclerosis complex (TSC) 2 and less frequently TSC1 genes. More recently a subtype of PEComa harboring TFE3 gene rearrangement, mutually exclusive with TSC complex mutations, has been identified. The bladder and the other genitourinary tract organs are an infrequent site of origin; to date, only 3 cases of primitive bladder PEComas, 1 prostatic PEComa, and 2 epithelioid angiomyolipomas of the kidney with TFE3 rearrangement have been described in literature. We report a bladder PEComa case with Xp11 rearrangement in a patient who previously had undergone chemotherapy for chronic lymphatic leukemia. We assessed the meaning of the presence of TFE3 rearrangement in genitourinary tract PEComas and the possible correlation of these uncommon lesions with previous chemotherapy. A better understanding of this entity's genetics may help suggest appropriate targeted therapy, which is still lacking in genitourinary tract PEComas.


Benzimidazole-based antibacterial agents against Francisella tularensis.
Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35-48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.


Associations between work environment and implicit rationing of nursing care: A systematic review.
To systematically evaluate the effect of working environment on implicit rationing of nursing care. Research has established direct and indirect associations between work environment and adverse patient outcomes. However, the causal nature of this relationship is uncertain, and implicit rationing has been proposed as a mediating factor between the work environment and patient outcomes. Eight databases were searched for articles published between May 2000 and May 2019. The reviewed articles provided evidence for the negative correlation between working environment and implicit rationing in 15 studies, and one of the studies showed that the correlation was not strong. There were differences in the levels of implicit rationing in different hospitals, units and shifts. The degree of influence of various factors in the working environment on implicit rationing is different. In addition, the working environment is only one of the factors that affects implicit rationing. Nursing managers initiatives to improve nurses' work environments should include improve nurses' perception of the adequacy of staffing and resources and improving teamwork to decrease nursing care left undone, so as to improve nurse outcomes and quality of care.


Five-year trends in patterns of drug use among people who use stimulants in dance contexts in the United Kingdom.
To describe and evaluate trends in the use of stimulant drugs over a 5-year period using an under-studied data collection method. Repeated-measures cross-sectional survey. Annual magazine-based survey targeting people who use stimulant drugs in dance contexts. Life-time use prevalence (ever used), age of first use, current use prevalence (any use within the last month) and extent of use within the last month (number of days used) for a range of stimulant drugs. Additional measures of quantity of ecstasy used were also collected. Trends in life-time and current prevalence over time have been detected and comparisons made between different stimulant drugs. Evidence is obtained of broad stability in patterns of stimulant use in respect of age of first use and frequency of use among ongoing users. Despite an apparent reduction in the current prevalence of ecstasy use, the proportion of heavy users (usually >4 pills per session) has more than doubled between 1999 and 2003. This purposively sampled population study has yielded time trend data broadly consistent with other indicators, where they exist, and also has demonstrable potential to identify new drug trends. Further comparisons of purposive samples and randomly formed samples are needed.


Effects of hydrogen sulphide on ischaemia-reperfusion injury and ischaemic preconditioning in the isolated, perfused rat heart.
Hydrogen sulphide (H(2)S) protects the heart against ischaemia-reperfusion injury caused by low flow or local ischaemia. We hypothesised that: (1) H(2)S protects against global ischaemia-reperfusion injury of the heart, (2) H(2)S plays a mechanistic role in ischaemic preconditioning, and (3) H(2)S acts by phosphorylation of protein kinases. Isolated, perfused rat hearts were used in two series. Series 1: group 1.1 (n=10), 40 min of ischaemia and 120 min of reperfusion, group 1.2 (n=7), like 1.1 except that 40 microM NaHS was added to the perfusate during stabilisation and throughout the experiment. Group 1.3 (n=10), like 1.1, but endogenously produced H(2)S was blocked by D,L-propargylglycine. Series 2: group 2.1 (n=10) control, 30 min of ischaemia followed by 120 min of reperfusion. Group 2.2 (n=10) ischaemic preconditioning before sustained ischaemia and 120 min of reperfusion. Group 2.3 (n=10) like 2.2 except of D,L-propargylglycine treatment like in group 1.3. Mitogen activated protein kinases including extracellular signal-regulated kinases (ERK 1/2), the stress-activated/c-Jun NH2 terminal kinases (JNK), P38, as well as protein kinase B/AKT (AKT), adenosine monophosphate dependent protein kinase (AMPK) and the inducible heat shock protein 72 were measured by Western blotting. Adenine nucleotides (ATP, ADP, and AMP) were measured by high-pressure liquid chromatography and energy charge was calculated. Infarct size was increased by D,L-propargylglycine (40+/-6 vs 27+/-10% in controls, p=0.03, Bonferroni post hoc test). There was a non-significant decrease in infarct size in the NaHS group (to 20+/-13%). Western blot analysis indicated an upregulation of heat shock protein 72 in the NaHS treated group and a reduced phosphorylation of AKT in the D,L-propargylglycine group. D,L-propargylglycine had no effect on ischaemic preconditioning or on phosphorylation of protein kinases (ERK, AKT, P38, JNK and AMPK) in preconditioned hearts. No difference in energy charge was found between groups, although ADP was increased in the NaHS-treated group. Endogenous H(2)S production protects against global ischaemia, and H(2)S may be a part of the endogenous cell defence. However, endogenous H(2)S did not appear to be important in ischaemic preconditioning, and protein kinases were not important for the effect of H(2)S. Exogenous H(2)S may provide myocardial protection, possibly acting by expression of heat shock protein 72.


The neuromuscular blocking properties of AH 8165 during halothane anaesthesia.
The time to onset, duration, time for reversal, and dose required to abolish twitch response for AH 8165 have been investigated. The drug is shown to be a rapidly acting agent, with a duration of action similar to pancuronium.


The Association of Clinician Characteristics with their Attitudes Toward Patients with Sickle Cell Disease: Secondary Analyses of a Randomized Controlled Trial.
A high level of evidence exists to suggest that negative attitudes held by clinicians toward persons with sickle cell disease serve as important barriers to the delivery of high quality care to this patient population. Little is known, though, about the characteristics of clinicians that may be predictive of these negative attitudes. During spring and summer 2009, we conducted a randomized controlled trial to test an intervention to improve clinician attitudes toward persons with sickle cell disease. Participating clinicians completed questionnaires regarding their demographic characteristics and their attitudes toward sickle cell patients. Principal clinician characteristics of interest included their race, professional discipline (nurse/physician), and the amount of their recent exposure to sickle cell patients in pain. Secondary analyses from this trial are presented here. Asian clinicians reported more negative attitudes towards these patients than did Black or White clinicians, nurses reported more negative attitudes than physicians, and clinicians with the greatest levels of recent exposure to sickle cell patients in pain reported more negative attitudes than did clinicians with lower levels of recent exposure. Our findings could facilitate the development of tailored educational resources needed to improve the quality of care delivered to persons with sickle cell disease, a national priority for sickle cell efforts.


Site-directed mutations at D1-His198 and D1-Thr179 of photosystem II in Synechocystis sp. PCC 6803: deciphering the spectral properties of the PSII reaction centre.
Site-directed mutations were constructed in photosystem II of Synechocystis sp. PCC6803 in which the axial ligand, D1-His198, of special pair chlorophyll PD1 was replaced with Gln and where D1-Thr179, which overlies monomeric chlorophyll ChlD1, was replaced with His. The D1-His198Gln mutation produces a 3nm displacement to the blue of the bleaching minimum in the Soret and in the Qy region of the (P+QA--PQA) absorbance difference spectrum. To a first approximation, the bleaching can be assigned to the low-energy exciton transition of the special pair chlorophylls PD1/PD2. The D1-Thr179His mutation produces a 2nm displacement to the red of the bleaching minimum in the Qy region of the (3P-1P) absorbance difference spectrum. Analysis of the flash-induced (P+QA--PQA) and (3P-1P) absorbance difference spectra of both mutants compared with wild-type at 80K indicate that the cation of the oxidized donor P+ is predominantly localized on the chlorophyll PD1 of the special pair and that the reaction centre triplet state, produced upon charge recombination from 3[P+Pheo-], when the primary quinone electron acceptor QA is doubly reduced, is primarily localized on ChlD1.


Epidemiological and virological studies on outbreaks of acute gastroenteritis associated with rotavirus in primary schools in Osaka.
There have been three recent outbreaks of acute gastroenteritis in primary schools in Osaka prefecture caused by rotavirus: one in a school (TA) in April, 1974 and two in two other schools (TE and K) in May 1975. The morbidity from the disease was 2.4--15.8% for all age groups in the schools, and 20.1--34.1% for a certain age group. The disease lasted for 4 (K) to 14 days (TE). The first cases in schools TA and TE were followed by successive cases. The main clinical symptoms were higher frequencies of diarrhea (68--71.4%) and fever (78%) than in winter vomiting disease. There was no difference in the incidences of the disease in boys and girls. From observation on the disease in individual families, the incubation period seemed to be 3 days. Using paired sera and Neonatal Calf Diarrhea Virus (NCDV) as antigen, positive seroconversion was demonstrated by the complement fixation test and marked seroconversion by the indirect fluorescent antibody technique. With these techniques, specific antibody to NCDV was detectable in the sera from an early stage of illness. Rotavirus was found on electron microscopic examination of some fecal specimens of patients in TA, but not in those of patients in TE or K, although adenovirus was isolated from one patient. A serological survey of healthy children aged 0 to 12 showed that rotavirus is a common virus in Osaka.


Effect of taste aversion learning on ethanol self-administration.
Ethanol (EtOH) oral self-administration studies using rats have had inconsistent outcomes: studies in which rats are fluid deprived report decreasing EtOH intake over trials, whereas studies not employing fluid deprivation report increasing intake over trials. The present study supports the hypothesis that differential taste aversion learning may account for some of this discrepancy. This study indicates that taste aversion learning is maximized under fluid deprivation conditions and that "latent inhibition," i.e., exposure to non-intoxicating amounts of the EtOH solution prior to conditioning, reduces taste aversion learning. It is suggested that the effect of fluid deprivation on taste aversion resulting from EtOH self-administration may be at least in part due to the development of latent inhibition in non-deprived animals during initial exposure to the EtOH solution.


Machine learning to determine the main factors affecting creep rates in laser powder bed fusion.
There is an increasing need for the use of additive manufacturing (AM) to produce improved critical application engineering components. However, the materials manufactured using AM perform well below their traditionally manufactured counterparts, particularly for creep and fatigue. Research has shown that this difference in performance is due to the complex relationships between AM process parameters which affect the material microstructure and consequently the mechanical performance as well. Therefore, it is necessary to understand the impact of different AM build parameters on the mechanical performance of parts. Machine learning (ML) models are able to find hidden relationships in data using iterative statistical analyses and have the potential to develop process-structure-property-performance relationships for manufacturing processes, including AM. The aim of this work is to apply ML techniques to materials testing data in order to understand the effect of AM process parameters on the creep rate of additively built nickel-based superalloy and to predict the creep rate of the material from these process parameters. In this work, the predictive capabilities of ML and its ability to develop process-structure-property relationships are applied to the creep properties of laser powder bed fused alloy 718. The input data for the ML model included the Laser Powder Bed Fusion (LPBF) build parameters used-build orientation, scan strategy and number of lasers-and geometrical material descriptors which were extracted from optical microscope porosity images using image analysis techniques. The ML model was used to predict the minimum creep rate of the Laser Powder Bed Fused alloy 718 samples, which had been creep tested at 650 ∘ C and 600 MPa. The ML model was also used to identify the most relevant material descriptors affecting the minimum creep rate of the material (determined by using an ensemble feature importance framework). The creep rate was accurately predicted with a percentage error of 1.40 % in the best case. The most important material descriptors were found to be part density, number of pores, build orientation and scan strategy. These findings show the applicability and potential of using ML to determine and predict the mechanical properties of materials fabricated via different manufacturing processes, and to find process-structure-property relationships in AM. This increases the readiness of AM for use in critical applications.


Labile proteins are necessary for T3 induction of growth hormone mRNA in normal rat pituitary and rat pituitary tumor cells.
Previous studies from our laboratory have shown that ongoing protein synthesis is required for L-tri-iodothyronine (T3) regulation of rat hepatic genes. In this report we have examined the role of ongoing protein synthesis in T3 regulation of the growth hormone gene (GH) in rat pituitary and GC cells. T3 (200 micrograms/100 g body weight injected intraperitoneally or 10(-8) M added to the media) induced a 3-fold rise of GH mRNA concentration after 8 h in rat pituitary (from 5.9 +/- 1% to 17.8 +/- 1.4% of an internal standard (IS), p less than 0.01) and a 5-fold rise in GC cells after 6 h (from 0.1 +/- 0.01% to 0.54 +/- 0.03% of IS, p less than 0.01). Cycloheximide (1 mg/100 g body weight intraperitoneally or 25 microM added to the media) completely blocked the increase in GH mRNA when given before the hormone in rat pituitary (7.5 +/- 0.5% of IS after 8 h) and GC cells (0.095 +/- 0.01% of IS after 6 h). Similar results were observed when emetine and puromycin were used to block protein synthesis. GH transcription rate in pituitaries from hypothyroid animals was 20 +/- 8 ppm and increased to a value of 295 +/- 85 parts per million 2 h after the injection of T3, and a similar 8-fold increase was observed in GC cells after 2 h. However, when cycloheximide was given before the hormone, the T3-induced increase in transcription was completely blocked. We also demonstrate here that the differences observed in GH transcription rate between hypo- and euthyroid rat pituitaries fully account for the differences observed in mRNA concentration. We conclude that short-lived proteins are involved in T3 regulation of the GH gene in rat pituitary and GC cells.


The increasing importance of Haemophilus influenzae in community-acquired pneumonia: results from a Danish cohort study.
Numerous studies have shown that the aetiology of community-acquired pneumonia (CAP) varies considerably among different healthcare settings. Because empiric therapies for CAP should cover the major pathogens, reports examining CAP aetiology are considered crucial, particularly in Nordic countries that still rely on penicillin G or V treatments for most patients with CAP. The primary objective of our study was to report CAP aetiology. Secondary objectives included the estimation of positivity rates for different tests and the odds of a positive test for various subgroups. In this cohort study, microbiological data were analysed for an overall cohort (variable degree of microbiological testing) and for a subgroup that was tested for both, bacteria, viruses and fungi, using routine methods (defined as extensive testing). The overall cohort comprised 2,264 patients, including 315 who were extensively tested. Bacterial and viral monoinfections were the most commonly identified infections. The dominant pathogen identified among extensively tested patients was Haemophilus influenzae (23.7%), followed by Streptococcus pneumoniae (20.6%). The tests with the highest positivity rates were sputum cultures (34.7%) and viral polymerase chain reaction (PCR, 24.4%). The odds of achieving a microbiological diagnosis increased significantly when extensive testing was performed compared with selective testing (OR 2.86, 95% CI 2.24-3.64). Our study indicated that H. influenzae is the dominant responsible pathogen for bacterial CAP in Denmark. Thus, we believe that the current treatment recommendations that encourage the use of penicillin G or V for the majority of patients with CAP need to be revised.


Two Rare Cases of Intrathoracic Splenosis and Subcutaneous Splenosis: Spleen Scintigraphy Avoided the Need for Invasive Procedures.
Splenosis is defined as the acquired heterotopic autotransplantation of splenic tissue in other sites of the body after splenic rupture, usually due to either traumatic or iatrogenic causes. It is often found incidentally and is usually asymptomatic. These implants are not limited to the left upper quadrant of the abdomen, however, and splenosis in other locations can mimic various pathologic entities. There are several reports on abdominal splenosis, but intrathoracic and subcutaneous splenosis are rare. We report two cases of intrathoracic and subcutaneous splenosis that were diagnosed using spleen scintigraphy, avoiding the need for an invasive procedure.


Constraints on natural global atmospheric CO2 fluxes from 1860 to 2010 using a simplified explicit forward model.
Land-use changes until the beginning of the 20(th) century made the terrestrial biosphere a net source of atmospheric carbon. Later, burning of fossil fuel surpassed land use changes as the major anthropogenic source of carbon. The terrestrial biosphere is at present suggested to be a carbon sink, but the distribution of excess anthropogenic carbon to the ocean and biosphere sinks is highly uncertain. Our modeling suggest that land-use changes can be tracked quite well by the carbon isotopes until mid-20(th) century, whereas burning of fossil fuel dominates the present-day observed changes in the isotope signature. The modeling indicates that the global carbon isotope fractionation has not changed significantly during the last 150 years. Furthermore, increased uptake of carbon by the ocean and increasing temperatures does not yet appear to have resulted in increasing the global gross ocean-to-atmosphere carbon fluxes. This may however change in the future when the excess carbon will emerge in the ocean upwelling zones, possibly reducing the net-uptake of carbon compared to the present-day ocean.


Effect of enzymatic interesterification on melting point of palm olein.
Immobilized PS-C 'Amano' II lipase was used to catalyze the interesterification of palm olein (POo) with 30, 50, and 70% stearic acid in n-hexane at 60 degrees C. The catalytic performance of the immobilized lipase was evaluated by determining the composition change of fatty acyl groups and triacylglycerol (TAG) by gas liquid chromatography and high-performance liquid chromatography, respectively. The interesterification process resulted in the formation of new TAGs, mainly tripalmitin and dipalmitostearin, both of which were absent in the original oil. These changes in TAG composition resulted in an increase in slip melting point, from the original 25.5 degrees C to 36.3, 37.0, and 40.0 degrees C in the modified POo with 30, 50, and 70% stearic acid, respectively. All the reactions attained steady state in about 6 h. This type of work will find great applications in food industries, such as confectionery.


Primary cardiac tumors on the verge of oblivion: a European experience over 15 years.
Primary tumors of the heart represent an exceedingly rare entity in cardiac surgery and literature regarding management and outcome is rare. The aim of this study was to translate 15 years of experience in both multimodal diagnosis and surgical treatment of one of the largest collective of patients in literature into a detailed analysis of patient prognosis, mean survival and best treatment approach. All patients who underwent open-heart surgery at the Hospital of the Medical University of Vienna for primary cardiac tumor excision between 1999 and 2014 were analyzed retrospectively. Mean follow-up was 76.8 months. Descriptive statistical measurements were applied. 113 patients were identified, 71 (62.8%) female and 42 (37.2%) male patients with a mean age of 57.9 ± 16.8 years. 90.3% (n = 102) masses were benign, 9.7% (n = 11) were malignant. Complete resection was possible for 99% and for 18.2% of benign and malignant masses, respectively. 2.9% of benign tumors and 45.5% of malignant tumors relapsed. The 30-day mortality was 1.8% (n = 2). Mean survival was 187.2 ± 2.7 months and 26.2 ± 9.8 months for benign and malignant pathologies, respectively. Sarcoma patients who underwent adjuvant combination-chemotherapy or adjuvant mono-chemotherapy and radiation had a statistically significant survival advantage of 41.5 months. Primary cardiac tumors remain challenging in the clinical setting. A multimodality treatment approach especially for sarcoma patients prolongs mean survival and should be regarded as the standard of care.


Effect of low dose phenylephrine infusion on shivering and hypothermia in patients undergoing cesarean section under spinal anesthesia: a randomized clinical trial.
Shivering is a common complication of spinal anesthesia. Phenylephrine, due to its peripheral vasoconstrictive effect, may limit the core to periphery redistribution of body temperature following spinal anesthesia, and reduce hypothermia and shivering. We hypothesized that prophylactic phenylephrine infusion would reduce shivering and hypothermia in women undergoing cesarean section under spinal anesthesia. A two-arm randomized, double-blind, placebo-controlled trial in term pregnant patients undergoing cesarean section. In the phenylephrine group (n=75) prophylactic phenylephrine infusion was administered at 25 µg/min immediately after initiation of spinal anesthesia and continued until the end of the operative period. In the placebo group (n=75) a normal saline infusion was administered during the same period. The primary outcome was the incidence of shivering; secondary outcomes were severity of shivering, changes in nasopharyngeal (core) temperature, and incidence of hypotension and bradycardia. The incidence of shivering in the phenylephrine and control groups was 24.0% (95% CI 14.3% to 33.7%) and 53.3% (95% CI 42.0% to 64.6%), respectively. The severity of shivering was greater in the control group (P=0.002) and the mean (±SD) end of surgery core temperature was significantly higher in the phenylephrine group (35.84°C ± 0.60) compared with controls (35.61°C ± 0.48) (P=0.009). The incidence of hypotension was higher in controls (53.4% vs. 2.7%; P <0.001) but bradycardia more frequent in group P (P=0.023). The incidence of shivering and degree of hypothermia were significantly reduced by a prophylactic phenylephrine infusion during cesarean section under spinal anesthesia.


The effects of long-term lead intoxication on the nervous system of the chicken.
In order to study the possible etiologic role of lead in human motor neuron disease we produced chronic lead intoxication in the chicken by daily administration of lead acetate. Control animals received sodium acetate. During life, periodic measurements were made of motor function, motor nerve conduction velocity and response amplitude. After sacrifice, histologic analysis was performed on spinal cord, peripheral nerve and muscle. A syndrome was produced characterized by a fall in motor response amplitude, spinal motor neuron degeneration, motor axonal loss and atrophy of muscle, similar to that seen in human motor neuron diseases.


Hemostatic efficacy of a flowable collagen-thrombin matrix during coronary artery bypass grafting: a double-blind randomized controlled trial.
Flowable hemostatic agents have the advantage of being able to be applied to irregular wound surfaces and difficult to reach areas. We sought to compare the effectiveness and safety of the flowable hemostatic sealants Collastat® (collagen hemostatic matrix, [CHM]) and Floseal® (gelatin hemostatic matrix, [GHM]) during off-pump coronary artery bypass (OPCAB). In this prospective, double-blind, randomized controlled trial, 160 patients undergoing elective OPCAB surgery were enrolled between March 2018 and February 2020. After primary suture of the aortocoronary anastomosis, an area of hemorrhage was identified, and patients received either CHM or GHM (n = 80, each). Study endpoints were the following: proportion of successful intraoperative hemostasis and time required for hemostasis overall postoperative bleeding, proportion of transfusion of blood products, and surgical revision for bleeding. Of the total patients, 23% were female, and the mean age was 63 years (range 42-81 years). Successful hemostasis proportion within 5 min was achieved for 78 patients (97.5%) in the GHM group, compared to 80 patients (100%) in the CHM group (non-inferiority p = 0.006). Two patients receiving GHM required surgical revision to achieve hemostasis. There were no differences in the mean time required to obtain hemostasis [GHM vs. CHM, mean 1.49 (SD 0.94) vs. 1.35 (0.60) min, p = 0.272], as confirmed by time-to-event analysis (p = 0.605). The two groups had similar amounts of mediastinal drainage for 24 h postoperatively [538.5 (229.1) vs. 494.7 (190.0) ml, p = 0.298]. The CHM group required less packed red blood cells, fresh frozen plasma, and platelets for transfusion than the GHM group (0.5 vs. 0.7 units per patient, p = 0.047; 17.5% vs. 25.0%, p = 0.034; 7.5% vs. 15.0%, p = 0.032; respectively). CHM was associated with a lower need for FFP and platelet transfusions. Thus, CHM is a safe and effective alternative to GHM. ClinicalTrials.gov, NCT04310150.


Performance and safety assessment of an integrated transmit array for body imaging at 7 T under consideration of specific absorption rate, tissue temperature, and thermal dose.
In this study, the performance of an integrated body-imaging array for 7 T with 32 radiofrequency (RF) channels under consideration of local specific absorption rate (SAR), tissue temperature, and thermal dose limits was evaluated and the imaging performance was compared with a clinical 3 T body coil. Thirty-two transmit elements were placed in three rings between the bore liner and RF shield of the gradient coil. Slice-selective RF pulse optimizations for B1 shimming and spokes were performed for differently oriented slices in the body under consideration of realistic constraints for power and local SAR. To improve the B1+ homogeneity, safety assessments based on temperature and thermal dose were performed to possibly allow for higher input power for the pulse optimization than permissible with SAR limits. The results showed that using two spokes, the 7 T array outperformed the 3 T birdcage in all the considered regions of interest. However, a significantly higher SAR or lower duty cycle at 7 T is necessary in some cases to achieve similar B1+ homogeneity as at 3 T. The homogeneity in up to 50 cm-long coronal slices can particularly benefit from the high RF shim performance provided by the 32 RF channels. The thermal dose approach increases the allowable input power and the corresponding local SAR, in one example up to 100 W/kg, without limiting the exposure time necessary for an MR examination. In conclusion, the integrated antenna array at 7 T enables a clinical workflow for body imaging and comparable imaging performance to a conventional 3 T clinical body coil.


Basaloid tumors arising from seborrheic keratosis: Malignant basal cell carcinoma or benign basaloid follicular hamartomatous proliferation?
Basaloid tumors arising from seborrheic keratosis (SK) that resembled basal cell carcinoma (BCC) were infrequently observed in our patients. They also exhibited morphologic features similar to those of trichoblastoma or basaloid follicular hamartoma. We retrospectively collected cases of SK with basaloid tumors from 2001 to 2017. Ten cases of BCC, five of nevus sebaceus with trichoblastoma, five of trichoblastoma, and five of trichoepithelioma were included as controls. Tumor-associated antigens Bcl-2, CD10, PHLDA1, and CK20 were tested. Antigenic markers CD34 and CD10 were used to analyze peritumoral stroma features and Ki-67 and pHH3 to measure the mitotic activity. Ten cases of SK with basaloid tumors were found and all located in non-sun-exposed areas, including five men and five women, with a mean age of 61 years. A distinct PHLDA1 staining was not observed. The staining patterns of basaloid tumor lobules associated with SK were similar to the benign control group. Bcl-2 staining in the tumor lobules was mostly negative. Peritumoral CD10 stain and CK20-positive Merkel cells in the lobules were observed and the mitotic counts were low. Basaloid tumors arising from SK are not always BCC. They were all benign follicular hamartomatous proliferation in this case series.


Udder shape and teat-end lesions as potential risk factors for high somatic cell counts and intra-mammary infections in dairy cows.
The association of common bacterial pathogens in milk samples during calving with udder shape or the presence of 'teat-end' lesions was investigated in 240 dairy cows from two herds. Sixty-three of 120 cows (53%) in one herd (herd A) and 54/120 animals (45%) in a second herd (herd B) had normal-shaped udders. The remaining animals had udder shapes defined as follows: large pendulous (18% herd A, 26% herd B); large between hindquarter (10% herd A, 17% herd B); overall small (8% herd A, 5% herd B); or small but pendulous (11% herd A, 7% herd B). At calving teat-end lesions were present in 63% and 76% of the quarters of herd A and B animals, respectively. There was no herd effect on udder shape or teat-end lesions. Analysis of variance revealed that udder shape and teat-end lesions did not have a significant association with quarter somatic cell count. However there was some association between mammary infection and udder shape and teat-end lesions. Compared to other udder shapes, cows with large between hindquarter shape had significantly less Staphylococcus aureus and Streptococcus uberis infection (P<0.001). There was a similar albeit less significant negative association with Escherichia coli infection (P<0.01). Infection with Streptococcus agalactiae and Streptococcus dysgalactiae was more frequent in cows with large pendulous and overall small udder conformations. The results also suggest an association between intra-mammary infection at calving and the presence of hyperkeratotic teat-end lesions, given that S. aureus, coagulase-negative staphylococci, S. uberis, S. agalactiae and E. coli were cultured from significantly more quarters with such lesions than from quarters without lesions or with other types of lesion (P<0.001).


Analysis of the growth phase-associated transcriptome of Streptococcus pyogenes.
Streptococcus pyogenes (group A streptococci, GAS) is a human pathogen which probably varies its multiplication rate and thus, growth phases in association with the type of infection caused in its host. To create a basis for future determinations of such associations, the genome-wide growth phase-related GAS transcriptome was assessed in the present study. Therefore, the published serotype M1 S. pyogenes genome sequence as well as the partially sequenced serotype M18 and M49 GAS genomes were used to produce DNA microarrays that carried 2256 oligonucleotide probes matching 3662 open reading frames (ORFs). With these microarrays, the transcriptome of the serotype M49 GAS strain 591 grown to the exponential, transition, and early stationary growth phases was assessed in seven independent experiments. The gained data were compared to real-time RT-PCR assays. Data analysis was refined by a novel approach, i.e. grouping of expressed genes to four classes according to relative transcript abundance and gene functions. At the different growth phases, 86.7%, 79.5% and 55.7% of the at least 1883 ORFs contained in the serotype M49 genome were expressed above the defined detection level. Contrary to the general trend, transcript amounts of genes in the functional groups of transport and membrane proteins as well as stress response factors peaked at the transition phase. The most prominent changes in the transcript abundances were predominantly observed for sugar compound transport and turnover-related ORFs. The majority of known virulence genes had their maximum expression during the transition phase, consistent with the proposed associated change in virulence behavior of the bacteria. With these results, it will now be feasible to assess the in situ growth phase of a given GAS strain during any type of infection by measuring the expression of selected marker genes.


Induction of sister chromatid exchanges by benzidine in rat and human hepatoma cell lines and inhibition by indomethacin.
The genotoxic activity of benzidine was studied in two cell lines derived from rat (H4) and human (HepG2) hepatomas which have been shown to be capable of activating certain promutagens. The responses were compared to results in two lung-derived fibroblast lines (IMR-90 and V79) which appear to have little or no metabolizing capability. Benzidine was found to induce sister chromatid exchanges in the two liver-derived cell lines in a dose-dependent fashion but failed to induce sister chromatid exchanges in the fibroblast lines. Since one proposed pathway for benzidine activation involves prostaglandin-mediated metabolism, we tested the effect of pretreatment with indomethacin, an inhibitor of this metabolic pathway. Indomethacin was highly effective in inhibiting benzidine-induced sister chromatid exchanges in both H4 and HepG2 cells. These results suggest that some DNA damage may occur in the livers of fast acetylating species such as the rat without prior N-acetylation and that some amount of DNA damage may occur in the livers of slow acetylating species, even when the liver is not the target organ for carcinogenesis.


Drug prescribing indicators in primary health care centers in Bahrain.
To estimate drug use indicators in primary health care centers in the Ministry of Health, Bahrain. Four out of 20 primary health care centers in Bahrain were selected and prescriptions of one day (July 30, 2003), were collected, reviewed and analyzed. The study showed that the average number of drugs per encounter was 2.6, while the percentage of prescriptions containing injections were 8.3%, and antibiotics were 26.2%. The percentage of drugs prescribed by generic name was 14.3%, and those from the National Drug List were 99.8%. Parameters, such as average number of drugs prescribed, are in line with many countries. However, injection prescribing was higher than European countries, but low in comparison with many countries in Asia and Africa. Antibiotic prescribing was close to European countries, and lower when compared to some Asian and African countries. We need an intervention program to promote the use of generic names, as it is quite low.


Contraindications to phenytoin in emergency department patients with seizures.
The objective of this study was to determine what contraindications to phenytoin exist in Emergency Department (ED) patients with a medical history of seizures. We conducted a retrospective chart review using ED medical records from 2005 at two network health care EDs. We identified potential patients through ICD-9 (International Classification of Diseases, Ninth Revision) codes, selected only adult patients with a prior documented history of seizures, and reviewed these charts. From 201 charts reviewed, the three most common antiepileptic drugs taken by patients were: phenytoin (38%), levetiracetam (17%), and valproic acid (15%). For absolute contraindications to phenytoin, 4.5% of seizure patients had a known hypersensitivity to phenytoin and 1.5% were pregnant; however, no pregnant patients were taking phenytoin and only 1 person with hypersensitivity to phenytoin was taking phenytoin. For relative contraindications, 6% of seizure patients had liver disease, 8% had kidney disease, 9% had alcohol use/dependence, and 16% had diabetes. However, 55% of those with liver disease, 44% with kidney disease, 77% with alcohol use/dependence, and 53% with diabetes were currently taking phenytoin. Very few seizure patients in the ED have absolute contraindications to the use of phenytoin, and most with absolute contraindications are taking other antiepileptic drugs. Conversely, a greater proportion of seizure patients have relative contraindications and many are continuing to use phenytoin.


Exercise-induced U-wave inversion as a marker of stenosis of the left anterior descending coronary artery.
The prevalence and cineangiographic correlates of exercise-induced inversion of U waves were studied in 248 patients. Exercise-induced U-wave inversion was observed in 36 patients (15%), of whom 35 had greater than or equal to 75% stenosis in one or more of the major coronary arteries. The proximal left anterior descending or left main coronary artery was involved in 33 of these patients, including 24 patients with no electrocardiographic evidence of anterior myocardial infarction. Exercise-induced U-wave inversion was observed in the absence of an abnormal resting 12-lead ECG. Only one of the 82 patients (1.2%) without significant coronary artery disease demonstrated exercise-induced U-wave inversion, and this patient had a primary cardiomyopathy. We conclude that exercise-induced inversion of the U-wave is highly predictiveof significant coronary artery disease and, more specifically, of disease of the proximal left anterior descending coronary artery.


The effects of excitotoxic lesions of the basal forebrain on the acquisition, retention and serial reversal of visual discriminations in marmosets.
The effects of N-methyl-D-aspartate-induced lesions of the basal forebrain (which included the cholinergic cells of the nucleus basalis of Meynert) were studied on three aspects of visual discrimination; learning, retention and reversal performance, in the marmoset. Neurobiological investigations revealed that the lesion produced large reductions in choline acetyltransferase activity within anterior regions of cortex, particularly prefrontal. In Experiment 1 lesioned animals showed impaired retention, one week after surgery, of a visual discrimination learned immediately prior to surgery and subsequently showed impaired performance over a series of reversals. The reversal deficit could be characterized as a tendency to perseverate on the previously correct stimulus on the first reversal and as a failure to show serial reversal learning on subsequent reversals. Acquisition of a novel discrimination was not impaired five weeks after surgery. As time of testing may have been a confounding factor, in Experiment 2 the effects of the same lesion on new learning were examined immediately following surgery and the effects on retention a month later. The lesion was found to disrupt new learning but did not affect retention. From the two experiments it is clear that, whereas disruption of retention and new learning was relatively transient, the impairments in reversal performance were more long lasting. In addition, lesioned animals exhibited behavioural hyperactivity and elevations in consummatory and schedule-controlled licking. The disinhibitory and preservative effects observed following lesions of the basal forebrain in this study are similar to those following lesions of the orbitofrontal cortex while the disruption of serial reversal learning is commonly seen following damage to the amygdala. Therefore, these results are consistent with the hypothesis that the range of behavioural effects of the lesion result from damage to the cholinergic afferents to orbitofrontal cortex and to the amygdala, two structures intimately connected to one another.


Patients with higher body mass index treated with direct / novel oral anticoagulants (DOAC / NOAC) for atrial fibrillation experience worse clinical outcomes.
Due to fixed dosing of direct oral anticoagulants (DOACs), uncertainty exists about their efficacy in a population of obese/overweight patients. We retrospectively investigated a real-life cohort of 325 DOAC anticoagulated patients with atrial fibrillation [179 receiving dabigatran (55%), 74 apixaban (23%) and 72 rivaroxaban (22%)]. Patients were stratified according to the body mass index (BMI) into non-obese (233 with BMI <30 kg/m2), class I obesity (71 with BMI 30-34.9 kg/m2) and class II + obesity (21 with BMI ≥35 kg/m2). Patients with higher BMI receiving DOACs were more likely to experience stroke/systemic embolism sooner (P = 0.043), experience major bleeding sooner (P < 0.001) and have shorter time to composite event consisting of thrombosis, bleeding or death (P < 0.001) whereas there was no significant association with overall survival (P = 0.470). BMI was significantly associated with thrombosis but not bleeding among dabigatran treated patients, and significantly associated with bleeding but not thrombosis among patients treated with factor Xa inhibitors. Associations of higher thrombotic, bleeding and composite endpoint risks with higher BMI remained statistically significant in multivariate Cox regression models adjusted for age, gender, eGFR, CHA2DS2VASC and HAS-BLED. Our findings indicate that obese patients receiving DOACs, especially ones with class II + obesity, might be under higher risks of stroke/bleeding depending on DOAC subtype. Loss of efficacy might be associated with dabigatran, whereas higher risk of major bleeding might be associated with factor Xa inhibitors.


Accuracy of the preoperative planning for cementless total hip arthroplasty. A randomised comparison between three-dimensional computerised planning and conventional templating.
A high accuracy was recently reported for the three-dimensional (3D) computerised planning of total hip arthroplasty (THA), comparing well with navigation regarding leg length and femoral offset. However, there is no randomised study comparing 3D preoperative planning with conventional 2D templating in terms of accuracy and clinical relevance. The 3D preoperative planning has a higher accuracy than the conventional 2D preoperative templating regarding the implants size and their positioning. A prospective comparative randomised study was carried out from 2008 to 2009, including two groups of 30 patients who underwent THA for primary osteoarthritis. One surgeon performed all the surgical procedures using a minimally invasive direct anterior approach. In one group, the planning was made on calibrated X-rays using 2D templates. In the other group, a CT-scan based 3D computerised planning was performed with dedicated software. The reconstructed hip final anatomy was compared postoperatively to the preoperative planning and the accuracy was expressed as the mean difference (±SD) between the planned positioning and the final positioning of the implants. The prediction rate for the stem and the cup sizes were respectively of 100% and 96% in the 3D group versus 43% for both components in the 2D group. When combining both components, the prediction rate was 96% in the 3D group versus 16% in the 2D group. In the 3D group, a high accuracy was achieved for the planning of the leg length (-1.8±3.6 mm ranging from -8 to+4mm) and the femoral offset (-0.07±2.7 mm ranging from -5 to+4mm) versus 1.37±6.4mm ranging from -9 to 13 mm and 0.33±5.7 mm (-16 to 11 mm) in the 2D templating group (P<0.0001). The 3D planning gives a higher accuracy than conventional 2D templating in forecasting the size of cup and the stem. This contributes to the prediction for leg length and offset that is more reliable with the 3D technique. This study suggests that 3D planning CT-scan data is an attractive alternative to navigation to restore these parameters. The high accuracy achieved by a low-experience surgeon suggests that 3D planning may help shorten the learning curve when using the minimally invasive direct anterior approach. Level III low-powered prospective randomized trial.


A novel chloroplast super-complex consisting of the ATP synthase and photosystem I reaction center.
Several 'super-complexes' of individual hetero-oligomeric membrane protein complexes, whose function is to facilitate intra-membrane electron and proton transfer and harvesting of light energy, have been previously characterized in the mitochondrial cristae and chloroplast thylakoid membranes. We report the presence of an intra-membrane super-complex dominated by the ATP-synthase, photosystem I (PSI) reaction-center complex and the ferredoxin-NADP+ Reductase (FNR) in the thylakoid membrane. The presence of the super-complex has been documented by mass spectrometry, clear-native PAGE and Western Blot analyses. This is the first documented presence of ATP synthase in a super-complex with the PSI reaction-center located in the non-appressed stromal domain of the thylakoid membrane.


The origin and fate of Merkel cell granules--an ultrastructural study.
In order to elucidate the origin and fate of Merkel cell granules (MCGs), electron microscopic studies were carried out in fetal rat skin at day 20 of gestation. In addition to the ordinary processing of the tissue, we incubated a part of the tissue with a solution containing ionophore A23187 in order to capture the rarely observable exocytotic event. Based on our findings, a hypothetical model for the life cycle of Merkel cell granules is proposed as follows: I) Granule morphogenesis takes place in the rough endoplasmic reticulum and the GERL, from where immature granules are budding off, thereby exhibiting a bristle-like coat. II) Maturation and storage of MCGs takes place in the cytoplasm. III) Following stimulation, MCGs are released. IV) After the exocytotic granule release, MCG membranes are retrieved in the form of coated pits.


Referential first mention in narratives by mildly mentally retarded adults.
Referential first mentions in narrative reports of a short film by 40 mildly mentally retarded adults and 20 nonretarded adults were compared. The mentally retarded sample included equal numbers of male and female, and black and white speakers. The mentally retarded speakers made significantly fewer first mentions and significantly more errors in the form of the first mentions than did nonretarded speakers. A pattern of better performance by black males than by other mentally retarded speakers was found. It is suggested that task difficulty and incomplete mastery of the use of definite and indefinite forms for encoding old and new information, rather than some global type of egocentrism, accounted for the poorer performance by mentally retarded speakers.


Improving the phenotype description of Basel-Vanagaite-Smirin-Yosef syndrome, MED25-related: polymicrogyria as a distinctive neuroradiological finding.
Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS) is an extremely rare autosomal recessive genetic disorder caused by variants in the MED25 gene. It is characterized by severe developmental delay and variable craniofacial, neurological, ocular, and cardiac anomalies. Since 2015, through whole exome sequencing, 20 patients have been described with common clinical features and biallelic variants in MED25, leading to a better definition of the phenotype associated with BVSYS. We report two young sisters, born to consanguineous parents, presenting with intellectual disability, neurological findings, and dysmorphic features typical of BVSYS, and also with bilateral perisylvian polymicrogyria. The younger sister died at the age of 1 year without autoptic examination. Whole exome sequencing detected a homozygous frameshift variant in the MED25 gene: NM_030973.3:c.1778_1779delAG, p.(Gln593Argfs). This report further delineates the most common clinical features of BVSYS and points to polymicrogyria as a distinctive neuroradiological feature of this syndrome.


Training physiotherapists to be responsive to their clients' health literacy needs.
To evaluate health literacy learning modules designed specifically for physiotherapists in private practice. Mixed-method design was used, evaluating pre-post physiotherapist health literacy knowledge and competencies using questionnaires and semi-structured interviews. One rural and one metropolitan private physiotherapy practice were recruited. Clients, physiotherapists, and other clinic staff. The OPHELIA (Optimizing Health Literacy and Access) process was applied to identify the health literacy needs of clients; co-design interventions; and implement and evaluate the interventions. The health literacy learning modules were co-designed with the physiotherapists and included one 3-h face-to-face workshop, followed by two 1-h videoconference workshops. Health literacy knowledge (rated 1-5 for 10 items, max score 50) and skills (rated 1-5 for 5 items, max score 25) were assessed before and after the workshops. Data were analyzed by paired t-test. Interviews were recorded, transcribed, and thematically analyzed. Health literacy knowledge of 19 health professionals improved after the workshop by 63% (pre 26.0 (7.5), post 41.0 (2.7), p < .001). Health literacy skills improved by 65% (pre 4.2 (3.3), post 21.8 (2.3), p < .001). We identified three themes from interview data: 1) 'the multi-faceted nature of health literacy requires multiple strategies'; 2) 'changing practice to promote understanding'; and 3) 'reflection on roles of multidisciplinary private practice.' Improvements in health literacy knowledge and skills are possible through post-graduate professional development. Workshops changed physiotherapists' understanding of their role in promoting health literacy.


Methotrexate-induced immune haemolytic anaemia.
A woman with metastatic breast carcinoma developed acute haemolytic anaemia on two occasions following treatment with methotrexate (MTX) and 5-fluorouracil (5-FU). The direct antiglobulin test was positive. Compatible control cells were pretreated with either MTX or 5-FU and subsequently incubated with patient and control sera. Agglutination in the indirect antiglobulin test was observed only in the presence of patient serum and MTX, and did not occur following pretreatment with 5-FU, folic acid, folinic acid or triamterene. There was no evidence of complement binding to the red cell surface. A macrophage assay showed increased phagocytic uptake of MTX-treated cells in the presence of patient serum. This phagocytosis was not enhanced by the addition of complement. The antibody subclass was predominantly IgG-3. The 51Cr red cell survival of autologous MTX cells was markedly shortened, indicating rapid in vivo destruction. These studies demonstrate the occurrence of acute haemolytic anaemia due to an IgG-3 antibody that reacts with erythrocytes in the presence of methotrexate. This antibody does not fix complement, but sensitizes red blood cells to phagocytosis by macrophages.


Enhancing effect of cerebral blood volume by mild exercise in healthy young men: a near-infrared spectroscopy study.
A mechanism by which exercise improves brain function may be attributed to increase in cerebral blood volume (CBV) with physical activity. However, the exact exercise intensity that influences CBV is still uncertain. To clarify this issue, 10 healthy young male participants were asked to perform a graded cycling exercise to the point of exhaustion while their prefrontal cortex CBVs are being monitored using near-infrared spectroscopy. Overall responsive cerebral oxygenation showed a non-linear pattern with three distinct phases. The CBV-threshold (CBVT), an event where rapid oxygenation takes place, occurred at approximately 42% of the V O2max. The CBVT preceded the lactate threshold (LT), which was at approximately 55% of the V O2max. The V O2max was not predictive of the CBVT in among the subjects. Our results indicate that oxygenation of the prefrontal cortex increases during graded cycling even at exercise intensities below the LT, suggesting the potential role of mild exercise in enhancing CBV.


Isolation and purification of six aristolochic acids with similar structures from Aristolochia manshuriensis Kom stems by pH-zone-refining counter-current chromatography.
Aristolochic acids (AAs), the major components in Aristolochia manshuriensis Kom stems (AMK), may cause Chinese herb nephropathy during clinical application. Therefore, it is necessary to distinguish AMK from other herbs and Chinese medicines using AAs with high purity as standards. So, an efficient method for separation and purification of AAs is required because of their similar structures. In this study, six AAs with purities of >98% were obtained by pH-zone-refining counter-current chromatography (PZRCCC) in a single run. The optimum two-phase solvent system was petroleum ether-ethyl acetate-methanol-water (3:7:3:7, v/v). Triethylamine (10 mM) was added to the aqueous mobile phase and trifluoroacetic acid (10 mM) to the organic stationary phase. As a result, 9.7 mg aristolochic acid IIIa, 12.0 mg aristolochic acid IVa, 32.2 mg aristolochic acid II, 103.7 mg aristolochic acid I, 24.6 mg aristolic acid II, and 26.1 mg aristolic acid I were obtained from 800 mg AAs crude extract. The elution order of AAs during PZRCCC separation corresponded with the pKa values and hydrophobicities of the target compounds. PZRCCC is an efficient method for isolation of AAs with similar structures.


The social dimensions of community delivery of intermittent preventive treatment of malaria in pregnancy in Madagascar, Mozambique, Nigeria and the Democratic Republic of the Congo.
Intermittent preventive treatment in pregnancy with sulphadoxine pyrimethamine (IPTp) is a key malaria prevention strategy in sub-Saharan African countries. We conducted an anthropological study as part of a project aiming to evaluate a community-based approach to the delivery of IPTp (C-IPTp) through community health workers (CHWs) in four countries (the Democratic Republic of Congo, Madagascar, Mozambique and Nigeria), to understand the social context in order to identify key factors that could influence C-IPTp acceptability. A total of 796 in-depth interviews and 265 focus group discussions were undertaken between 2018 and 2021 in the four countries with pregnant women, women of reproductive age, traditional and facility-based healthcare providers, community leaders, and relatives of pregnant women. These were combined with direct observations (388) including both community-based and facility-based IPTp delivery. Grounded theory guided the overall study design and data collection, and data were analysed following a combination of content and thematic analysis. A series of key factors were found to influence acceptability, delivery and uptake of C-IPTp in project countries. Cross-cutting findings include the alignment of the strategy with existing social norms surrounding pregnancy and maternal health-seeking practices, the active involvement of influential and trusted actors in implementation activities, existing and sustained trust in CHWs, the influence of husbands and other relatives in pregnant women's care-seeking decision-making, the working conditions of CHWs, pregnant women's perceptions of SP for IPTp and persistent barriers to facility-based antenatal care access. The findings provide evidence on the reported acceptability of C-IPTp among a wide range of actors, as well as the barriers and facilitators for delivery and uptake of the intervention. Overall, C-IPTp was accepted by the targeted communities, supporting the public health value of community-based interventions, although the barriers identified should be examined if large-scale implementation of the intervention is considered.


Effects of thymidine analogs on Syrian hamster melanoma cells: phenotypes arising from selection for analog resistance.
In order to compare the biological effects of different thymidine (dT) analogs, two unusual cell lines (B-4 and HAB) previously isolated from a Syrian hamster melanoma line by selection with 5-bromodeoxyuridine (BrdU) were analyzed for their response to other analogs. B-4 cells require high concentrations of BrdU for optimal growth, and it was seen that the requirement for BrdU could be satisfied partially by 5-chlorodeoxyuridine (CldU) but not by the other dT analogs tested. HAB cells are able to grow with all the dT residues in nuclear DNA replaced by BrdU, and it was found that they could also grow with essentially all the dT residues in nuclear DNA replaced by CldU but not by other analogs. New cell lines resistant to 100 micrometer concentrations of CldU, 5-iododeoxyuridine (IdU), and 5-hydroxymethyldeoxyuridine (HMdU) were isolated from the melanoma line and tested for cross-resistance to the other dT analogs. A high level of cross-resistance was observed only with BrdU and CldU. The ability of the cell lines resistant to BrdU, CldU, and IdU to incorporate these analogs into nuclear DNA also was determined. BrdU and CldU were incorporated efficiently by all of the lines tested, but the IdU-resistant cells seemed to preferentially exclude IdU.


Presence of two isoforms of Na, K-ATPase with different pharmacological and immunological properties in the rat kidney.
Previous studies have demonstrated the presence of two populations of Na,K-ATPase with distinct kinetic, pharmacological and immunological characteristics along the rabbit nephron, indicating that the proximal segments of the nephron express exclusively the alpha 1 isoform of the catalytic subunit, whereas the collecting duct expresses an alpha 3-like isoform. Because pharmacological studies have shown the existence of two populations of Na,K-ATPase with different sensitivities to ouabain in the rat cortical collecting duct, which may result from the presence in the same nephron segment of the two isoforms demonstrated in the different segments of the rabbit nephron, the present study was undertaken to characterize the properties of Na,K-ATPase along the rat nephron. Results indicate that each segment of the rat nephron contains two subpopulations of Na,K-ATPase: a component highly sensitive to ouabain (IC50 approximately 5.10(-6) M) which is recognized by an anti-alpha 3 antibody and another moiety of lower affinity for ouabain (IC50 approximately 5.10(-4) M) which is recognized by an anti-alpha 1 antibody. Whether these two subpopulations correspond to different isoforms of the alpha subunit of Na,K-ATPase (alpha 1 and alpha 3-like) remains to be determined.


Acute effects of cigarette smoking on the QT interval in healthy smokers.
This study assesses the effect of a first cigarette smoked in the morning on the QT interval duration in healthy habitual smokers after not smoking overnight. This study demonstrates that although after cigarette smoking the QT(Bc) values increase, the QT(Fc) and QT(Lc) values remained unchanged, and an increased sympathetic response was evident. The discrepancies between the results seen by different QT correction formulas emphasize the importance of selecting an accurate method for heart rate correction when evaluating and interpreting alterations in QT values.


Morphological and proliferative responses of cultured Schwann cells following rapid phagocytosis of a myelin-enriched fraction.
Cultured Schwann cells were found to phagocytose exogenously applied myelin membranes within 1 h. However, the resulting proliferative response required an additional 9 h of incubation. Treatment with ammonium chloride, a lysosomal inhibitor, delayed the appearance of the proliferative response to the myelin membranes by 12 h. Processing of myelin within the Schwann cells was followed by the appearance of immunocytochemically detectable myelin basic protein which was first visible at 4 h. Similar to the proliferative response, the appearance of immunoreactive material was delayed by the addition of ammonium chloride. Schwann cells were observed initially to ingest myelin fragments at their distal-most tips after which time the myelin phagosomes collected in the perinuclear region and fused with lysosomes. Phagocytic Schwann cells had a notable increase in Golgi membranes and microfilaments and contained widely dilated, rough endoplasmic reticulum cisternae. In purified cell cultures, Schwann cells phagocytosed myelin slower than macrophages, but displayed phagocytic abilities much greater than fibroblasts. The ability of cultured Schwann cells to phagocytose myelin rapidly suggests that these cells may aid in the breakdown and removal of myelin during Wallerian degeneration. These data further confirm the mitogenic effect of myelin and its possible role during nerve regeneration.


Rapid and efficient uranium(VI) capture by phytic acid/polyaniline/FeOOH composites.
Uranium plays an indispensable role in nuclear energy, but there are limited land resources to meet the ever growing demand; therefore, a need exists to develop efficient materials for capturing uranium from water. Herein, we synthesize a promising adsorbent of phytic acid/polyaniline/FeOOH composites (PA/PANI/FeOOH) by oxidative polymerization. Phytic acid, acting asa gelator and dopant, plays an important role in the formation of polyaniline (PANI). The PA/PANI/FeOOH exhibites high adsorption capacity (qm=555.8mgg-1, T=298K), rapid adsorption rate (within 5min), excellent selectivity and cyclic stability. In addition, the results show that the adsorption isotherm is well fitted to the Langmuir isotherm model, and the adsorption kinetics agree with a pseudo-second order model. XPS analysis indicates that the removal of uranium is mainly attributed to abundant amine and imine groups on the surface of PA/PANI/FeOOH. Importantly, the removal of uranium from low concentrations of simulated seawater is highly efficient with a removal rate exceeding 92%. From our study, superior adsorption capacities, along with a low-cost, environmentally friendly and facile synthesis, reveal PA/PANI/FeOOH asa promising material for uranium capture.


The effects of opiate agonist and antagonist on serum prolactin in primates: possible role for endorphins in prolactin regulation.
Intravenous administration of the opiate receptor antagonist naloxone produced a significant reduction in basal serum PRL concentrations in four male Macaca arctoides. Significant decreases from basal levels were found 15, 30, 45, 60, 90, 120, 150, and 180 min after the iv injection of 0.05 and 0.25 mg/kg naloxone. The iv administration of 0.4 mg/kg morphine produced rapid and significant increases in PRL levels, while 0.04 mg/kg morphine or saline produced no change. Both the dopamine receptor-stimulating agent apomorphine (0.15 mg/kg) and naloxone (0.25 mg/kg) decreased basal serum PRL and blocked the morphine-induced increases in serum PRL. These data support the hypothesis that endorphins are involved in the stimulation of PRL secretion.


A case of mucinous cystic neoplasm of the liver: description of Sonazoid-enhanced ultrasound imaging and histopathologic findings.
Mucinous cystic neoplasms (MCNs) of the hepatobiliary system are rare tumors that usually arise within the liver. We encountered a 63-year-old woman with a surgically proven MCN of the liver. We first performed contrast-enhanced ultrasound imaging, and the mass was found to have the appearance of a solid tumor, showing peripheral nodular enhancement in the arterial and portal phases with persistence of enhancement. The lesion remained enhanced in the post-vascular phase (Kupffer phase). Based on these findings, we incorrectly identified the tumor as a cavernous hemangioma, despite negative findings in computed tomography and magnetic resonance imaging. In our immunohistologic analysis using anti-CD68 antibody, the antibody-positive cells were identified as macrophages. Therefore, the Sonazoid microbubbles could have been retained within these macrophages, resulting in late enhancement. These findings appear to be of key importance in accurately diagnosing MCNs and clarifying their pathophysiology.


Characterization of two murine monoclonal antibodies reactive with human B cells. Their use in a high-yield, high-purity method for isolation of B cells and utilization of such cells in an assay for B-cell stimulating factor.
We describe two monoclonal antibodies, HH1 and HH2. Both reacted selectively with surface immunoglobulin (sIg)-positive human B cells. Both antibodies stained on average 7-8% of peripheral blood mononuclear cells. They have not been found to react with cells or cell lines of other haematopoietic cell lineages, except that HH2 was positive on a small percentage of cells of the erythroid cell line K562. The molecular weight of the HH1 antigen was 95 kD, as established by Western blotting. Neither of these two antibodies reacted with Ig determinants, Fc receptors, complement receptors, or known class-I or class-II molecules. A combination of these antibodies was used in a direct panning technique for high-yield enrichment of normal B lymphocytes from peripheral blood. The enriched B cells could be further purified by lysis of T cells (final yield, on average 72 +/- 8% of initial B cells) or by a second panning (yield, 35 +/- 11%). The purified B cells contained less than 1% contaminating T cells and less than 0.5% monocytes and were used in an assay for B-cell-stimulating factor which they showed a normal and very reproducible proliferative response.


Effect of splenectomy on the progression of postoperative pulmonary metastases of the 3LL tumor.
Surgical excision of the local intrafootpad tumor of the 3LL lung carcinoma is followed by accelerated growth of its lung metastases. When, however, splenectomy was performed concomitantly with tumor excision, the acceleration of lung metastases was prevented. In cases where excision of the local tumor took place when it reached large sizes, concomitant splenectomy did not prevent the accelerated growth of the lung metastases. If, however, at these stages of tumor growth splenectomy was performed 3 days prior to the excision of the tumor, it did prevent the accelerated growth of metastases. Intrafootpad reinoculation of tumor cells following tumor excision and splenectomy caused further reduction in metastatic growth. The results suggest that existence of two possible distinct mechanisms which control metastatic growth: the local tumor might exert non-immunologically, an inhibitory effect on its lung metastases, and the spleen, possibly via suppressor lymphocytes, may suppress an immune effector activity against the tumor metastases, an activity which is manifested following splenectomy.


Routine radiographs at time of pin removal after closed reduction and percutaneous pinning for type 2 supracondylar humerus fractures do not change management: a retrospective cohort study.
Radiographs are usually taken on day of pin removal for children treated with closed reduction and percutaneous pinning (CRPP) of type 2 supracondylar humerus fractures. The purpose of this study was to determine whether radiographs taken at time of pin removal for patients recovering uneventfully alter management. After IRB approval, billing records identified 1213 patients aged 1-10 years who underwent elbow surgery between 2007 and 2013 at our institution for a supracondylar humerus fracture. Of these patients, 389 met inclusion criteria. Clinical charts were reviewed for demographics, operative details, and clinical follow-up, focusing on clinical symptoms present at pin removal. Radiographs taken at time of pin removal and subsequent visits were assessed for healing and fracture alignment. In no case was pin removal delayed based on radiographs. One hundred and nineteen (31 %) patients had radiographs taken following pin removal; in no case was loss of reduction found among these patients. No cases of neurologic or vascular injury, re-fracture, or loss of reduction occurred. Infection occurred in 12 patients (3 %). Pins were kept in place for 23.8 ± 4.4 days. Eighty-six patients (22 %) had additional intervention after pin removal (cast application in all cases). Of 389 patients, 75 (19 %) had no documented reason for extended casting, four (1 %) were extended based on physician evaluation of radiographs, and seven (2 %) were extended for other reasons. Elimination of radiographs at time of pin removal should be considered. If continuing to obtain radiographs at pin removal, we recommend removing pins before taking radiographs to reduce patient fear and anxiety from visualizing percutaneous pins.


Reactivation of herpes zoster after liver biopsy.
A patient developed reactivation of herpes zoster infection (shingles) after a routine liver biopsy. Reactivation of herpes is often related to trauma. This entity should be considered when patients report postbiopsy pain inappropriate to the procedure. If the typical rash of shingles develops, antiviral therapy should be considered.


Transoral Approach for Odontoidectomy Efficacy and Safety.
Odontoid process pathologies can cause upper motor neuron lesions. These pathologies can be approached through either a high retropharyngeal approach or a transoral approach. The introduction of the surgical microscope, proper instrumentations, and proper antibiotics has increased utilization of the transoral approach. Our approach to anterior odontoid resection through transoral approach for different pathologies resulting in compression the cervical cord or causing craniocervical instability is described here. We aim to explore the safety and efficacy of this approach. Twenty cases of different odontoid pathologies were managed by transoral surgery. Patients were assessed clinically for axial neck pain and radicular symptoms using visual analog scale. The Nurick score was used to get an overall functional evaluation of the difficulty of ambulation and walking. Radiological evaluation of the patients included plain radiographs, CT scans, and MRI of the cervical spine. Posterior surgery was done as a first stage for restoring the sagittal profile of the cervical spine. Transoral surgery was done as a second stage for odontoid resection and anterior decompression of the cord. Average follow-up was 29.4 ± 3.8 months. Mean preoperative Nurick scale was 1.3 ± 1.2. Mean postoperative Nurcik scale was 0.5 ± 0.61. Patients with axial neck pain were improved after surgery except the 6 patients; mean VAS preoperative 8.2 ± 2.3 SD, mean postoperative VAS 3.7 ± 0.8SD, and radicular symptoms were not significantly changed after surgery; gait changes were improved in all patients with preoperative gait disturbance. The transoral approach is a safe and effective surgical method for the direct decompression of ventral midline extradural compressive disease of the craniovertebral junction.


Diagnostic value of p16 and Ki-67 expression in cervical glandular intraepithelial disease: A review.
Cervical adenocarcinoma has been increasing in frequency, particularly among young women. Its diagnosis still presents many challenges. In addition to the difficulty in accessing the lesion, the lack of well-established criterias for cytological and histological diagnosis, and colposcopic images that are often not very clear, there are many benign situations that mimic glandular diseases. Immunohistochemistry has been used to aid this diagnosis. The purpose of this review is to evaluate the data available in the literature related to the use of p16 and Ki-67 as an auxiliary tool in the diagnosis of glandular disease. Original articles were searched in the PUBMED/MEDLINE, EMBASE, SCOPUS and BVS using different combinations of keywords and descriptors. Of the 83 initial articles, 10 were selected. The criterias used for immunohistochemical interpretation showed many differences. The studies compared benign pathologies to malignant pathologies and some used panels with different immunomarkers while others used only p16. P16 showed an intense staining pattern in malignant pathologies, despite some studies have shown a negative pattern in adenocarcinoma. This can be explained by the histological subtype, not always related to HPV. Some studies have shown immunopositivity for p16 in normal tissues, tubal metaplasia and cervical endometriosis, but the staining pattern was never intense, as in malignant tissues. Ki-67 showed a more intense staining in AIS and adenocarcinoma tissues and was also present in normal tissues, mainly in tubal metaplasia and cervical endometriosis. Biomarkers have proved to be important tools in aiding the diagnosis of glandular lesions, either alone or in panels. Standardization in the interpretation of immunochemistry is required.


Over the river, through the woods: cognitive maps in the hippocampus and orbitofrontal cortex.
The hippocampus and the orbitofrontal cortex (OFC) both have important roles in cognitive processes such as learning, memory and decision making. Nevertheless, research on the OFC and hippocampus has proceeded largely independently, and little consideration has been given to the importance of interactions between these structures. Here, evidence is reviewed that the hippocampus and OFC encode parallel, but interactive, cognitive 'maps' that capture complex relationships between cues, actions, outcomes and other features of the environment. A better understanding of the interactions between the OFC and hippocampus is important for understanding the neural bases of flexible, goal-directed decision making.


Sidewinder catheter for conversion of retrograde into antegrade catheterization.
Conversion of retrograde into antegrade catheterization is accomplished through the use of a sidewinder catheter with a reformed loop that is subsequently lost during advancement of the catheter tip. This technique was used to perform eight percutaneous dilatations (PTD) in seven patients (one had bilateral disease). Other applications for antegrade catheterization are considered.


Wnt1-inducible signaling protein 1 regulates laryngeal squamous cell carcinoma glycolysis and chemoresistance via the YAP1/TEAD1/GLUT1 pathway.
Wnt1-inducible signaling protein 1 (WISP1) is a matricellular protein and downstream target of Wnt/β-catenin signaling. This study sought to determine the role of WISP1 in glucose metabolism and chemoresistance in laryngeal squamous cell carcinoma. WISP1 expression was silenced or upregulated in Hep-2 cells by the transfection of WISP1 siRNA or AdWISP1 vector. Ectopic WISP1 expression regulated glucose uptake and lactate production in Hep-2 cells. Subsequently, the expression of glucose transporter 1 (GLUT1) was significantly modulated by WISP1. Furthermore, WISP1 increased cell survival rates, diminished cell death rates, and suppressed ataxia-telangiectasia-mutated (ATM)-mediated DNA damage response pathway in cancer cells treated with cisplatin through GLUT1. WISP1 also promoted cancer cell tumorigenicity and growth in mice implanted with Hep-2 cells. Additionally, WISP1 activated the YAP1/TEAD1 pathway that consequently contributed to the regulation of GLUT1 expression. In summary, WISP1 regulated glucose metabolism and cisplatin resistance in laryngeal cancer by regulating GLUT1 expression. WISP1 may be used as a potential therapeutic target for laryngeal cancer.


Construction of an evaluation index system for undergraduate nursing teachers' curriculum humanistic competence: a Delphi study in China.
The curriculum humanistic competence of nursing teachers is important to cultivate the humanistic qualities of undergraduate nursing students. However, there are no evaluation tools for the curriculum humanistic competence of undergraduate nursing teachers in China. To develop an index system to evaluate the curriculum humanistic competence of undergraduate nursing teachers. This research conducted a Delphi study. Semi-structured interviews were held with 19 experts, and Delphi rounds were conducted with 18 experts. This study was conducted in 12 universities and 4 Grade A tertiary hospitals in China. A literature review and semi-structured interviews were conducted to develop an initial framework. A two-round Delphi survey was employed to build the index system for undergraduate nursing teachers' curriculum humanistic competence. After two rounds of consultation, the index system included 5 first-level indicators, 11 second-level indicators and 41 third-level indicators. The Cr for two rounds of consultation were 0.929 and 0.923, and Kendall's W was 0.152(P<0.001). The index system for the evaluation of undergraduate nursing teachers' curriculum humanistic competence offers guidelines for undergraduate nursing teachers in China. It can be used in practice to develop high humanistic qualities in undergraduate nursing teachers.