High-throughput multiplex MIRU-VNTR typing of Mycobacterium bovis.
Spoligotyping is the most widely used method for genotyping Mycobacterium bovis (M. bovis). However, its discriminatory power varies widely between countries. MIRU-VNTR typing could be a promising alternative, although it generally requires the time consuming and laborious simplex PCR assays using standard agarose gel electrophoresis. The accuracy of this approach depends on good standardization and a certain degree of expertise. This study presents a version of MIRU-VNTR based on three triplex PCRs with automatic allelic assignation of the products analyzed in capillary electrophoresis. The technique was prospectively applied to 44 M. bovis and two Mycobacterium caprae (M. caprae) isolates, and 22 different MIRU-VNTRtypes were obtained; with spoligotyping, only 14 different types were obtained. The proposal makes it possible to shorten response times, automate procedures, and increase accuracy, thus minimizing errors in assigning genotypes. It would enable the switch from a standard limited method of genotyping M. bovis to a high-throughput discriminatory fingerprinting approach.


The earliest case of retinopathy of prematurity?
Retinopathy of prematurity (ROP) is a well-recognized condition in premature babies born today and in the recent past. One would not normally expect to come across evidence of its existence among older patients. We present a case of apparent regressed ROP in a lady born in May 1939, prior to the documented reports of the first cases.


Pathophysiology and management of acute gastric mucosal hemorrhage.
Unlike hemorrhage from peptic ulcer, surgical management for hemorrhage from stress ulcer is not necessarily successful on many occasions. Thus, the most important thing one can try is to prevent the development of this condition. Forty eight patients admitted to the Shock and Trauma Unit, Hahnemann Medical College and Hospital, who had a primary diagnosis of shock were divided into three groups: group 1 received the standard shock regimen plus large dose steroid therapy repeated every four hours for 36 hours; group 2 received the standard shock regimen plus small dose steroid therapy repeated every four hours for 96 hours; group 3 received the standard shock regimen without the addition of steroids. There was a 57.9 per cent incidence of acute gastric ulceration in those shock patients not treated with steroids (group 3) compared with 33.3 per cent incidence of gastric ulceration in group 2 and 5.9 per cent incidence in group 1. The use of pharmacologic doses of steroids early in the shock state for period of less than 36 hours seems to reduce the incidence of gastric ulceration and hemorrhage in low flow states associated with septic, cardiogenic and hemorrhagic shock.


[Unreamed interlocking intra medullary nailing in treating tibial and fibular fractures].
To report the experience in the use of unreamed interlocking intramedullary nails. From 1995 to 1997, 54 tibial and fibular fractures were treated with unreamed interlocking intramedullary nails they included open fractures (9 cases) and close fractures (45). All fractures healed within 6 months and showed good knee and ankle joint functions. Slight postoperation infection was found in one of the open fractures. Incomplete injury of peroneal nerve was noted in 1 case. Unreamed interlocking intramedullary nail can be used to treat diaphyseal fractures effectively. It can protect the soft tissue envelope around the fracture and prerent local blood supply from further damaginge.


Atlanto axial rotatory fixation--a cause of torticollis.
Atlanto-axial rotatory fixation is a rare but important cause of persistent torticollis. The diagnosis is confirmed by careful radiological examination of the atlanto-axial joint, also employing tomography if necessary. Treatment is skull traction in an attempt to improve the position followed by posterior atlanto-axial fusion to prevent further, and potentially disastrous, displacement. Atlanto-axial dislocation or subluxation should be looked for in all cases of acute torticollis, when reduction by traction will most likely be successful and prevent the development of atlanto-axial rotatory fixation and the associated persistent torticollis.


Epidemiologic and ecologic characteristics of some diseases transmitted by arthropods on the littoral of the Republic of Croatia.
To show epidemiologic and ecologic characteristics of some diseases transmitted by arthropods on the littoral of the Republic of Croatia. The pattern of infectious diseases that are transmitted exclusively by vectors was monitored during the period 1985 to 1999. Data on the incidence of the diseases in the Republic of Croatia as a whole and available data on the presence of the vectors for the diseases on the littoral are presented for comparison. Mediterranean spotted fever, murine typhus, Lyme disease, cutaneous and visceral leishmaniasis, and pappataci fever occur sporadically on the Croatian littoral. Tick-borne meningoencephalitis is endemic in the northwestern part of Croatia but is not present on the littoral. Twelve cases of malaria are imported into Croatia per year on average. Diseases transmitted by arthropods are not a major public health problem in Croatia. The medically relevant entomofauna of Croatia has not yet been adequately investigated.


Phosgene as a derivatizing reagent prior to gas and liquid chromatography.
The use of phosgene as a derivatizing agent for bifunctional compounds prior to gas and liquid chromatographic analysis is reviewed. Applications include gas chromatographic determinations of metoprolol and its metabolites in biological fluids, enantiomeric separations of beta-blocking drugs and sympathomimetic agents on a chiral stationary phase and liquid chromatographic enantiomer separations.


Exploring principles of hibernation for organ preservation.
Interest in mimicking hibernating states has led investigators to explore the biological mechanisms that permit hibernating mammals to survive for months at extremely low ambient temperatures, with no food or water, and awaken from their hibernation without apparent organ injury. Hibernators have evolved mechanisms to adapt to dramatic reductions in core body temperature and metabolic rate, accompanied by prolonged periods without nutritional intake and at the same time tolerate the metabolic demands of arousal. This review discusses the inherent resilience of hibernators to kidney injury and provides a potential framework for new therapies targeting ex vivo preservation of kidneys for transplantation.


[Metatarsalgia: Differential diagnosis and therapy].
Metatarsalgia refers to localized or generalized forefoot pain in the region of the metatarsal heads. Symptoms can be isolated or in combination with accompanying deformities occurring in the forefoot and/or hindfoot. Anamnesis and clinical investigation usually yield to the diagnosis, the underlying cause on the other hand is not always easy to identify. In the foreground of the treatment is the exhaustion of conservative forms of therapy to minimize the symptoms of local pressure increase and callus under the metatarsal heads. In addition, various surgical methods are available, such as corrective osteotomy of the metatarsale bone, soft tissue interventions and the correction of associated deformities. The indications for surgical intervention should be made with caution in order to avoid failures and complaints persisting after surgery. The most common problems are an inadequate indication for surgery, technical problems and insufficient postoperative treatment.


The importance of rigid nasal endoscopy in the diagnosis and treatment of rhinolithiasis.
Rhinolithiasis is the presence of mineralized and calcareous formations located in the nasal cavity. They have rare occurrence and can be easily confused with infection or obstruction of upper airways. If they are undetected for a long time, they may grow large enough to cause of nasal obstruction, mimicking sinusitis. Seven cases of rhinolithiasis were presented, and their diagnosis was made by rigid endoscopic nasal examination. Also computerized tomography scan was used to describe the size and site of the rhinoliths accurately. Our purpose was to determine the role of rigid nasal endoscopy in the diagnosis and the treatment of rhinolithiasis. In this study, seven cases of rhinolithiasis, who were diagnosed and treated by rigid nasal endoscopy were presented. Between January 2000 and November 2004, seven cases (four males and three females; age ranged from 8 to 45 years) with rhinolithiasis were diagnosed. The most frequent symptoms were nasal obstruction with purulent rhinorhea, nasal and oral malodor. As complementary examinations, computerized tomography and simple X-ray of paranasal sinuses were used to locate and measure the dimension of calcareous mass, and to reveal possible invasion of the adjacent structures. The removal of rhinolithiasis was done with rigid nasal endoscopy under topical anesthesia in six cases and general anesthesia in one case. Rhinolithiasis is a rare condition but must always be suspected in patients with long standing nasal obstruction, nasal and oral malodor, purulent rhinorrhea and chronic headache.


Vitamin D in chronic kidney disease.
Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease (CKD) population. CKD is characterized by dysregulation of vitamin D and mineral metabolism. Secondary hyperparathyroidism and its management puts patients with CKD at increased cardiovascular risk. Emergence of experimental and some clinical data suggesting beneficial effects of vitamin D on proteinuria, blood pressure, inflammation and cardiovascular outcomes has pushed it to the center stage of CKD research. Pediatric data on vitamin D dysregulation and its consequences are still in its infancy. Ongoing prospective studies such as Chronic Kidney disease in Children (CKiD) and the Cardiovascular Comorbidity in Children with CKD (4 C) should help to delineate the evolution of disturbances in mineral metabolism and its adverse effects on growth, CKD progression and cardiovascular outcomes.


Evidence-based updates to the 2021 Surviving Sepsis Campaign guidelines Part 2: Guideline review and clinical application.
NPs should be prepared to screen for sepsis, initiate treatment, and optimize care for sepsis survivors. The 2021 Surviving Sepsis Campaign guidelines offer best practices for identification and management of sepsis and septic shock. This article, second in a 2-part series, presents evidence updates and discusses implications for NPs.


Machine learning model from a Spanish cohort for prediction of SARS-COV-2 mortality risk and critical patients.
Patients affected by SARS-COV-2 have collapsed healthcare systems around the world. Consequently, different challenges arise regarding the prediction of hospital needs, optimization of resources, diagnostic triage tools and patient evolution, as well as tools that allow us to analyze which are the factors that determine the severity of patients. Currently, it is widely accepted that one of the problems since the pandemic appeared was to detect (i) who patients were about to need Intensive Care Unit (ICU) and (ii) who ones were about not overcome the disease. These critical patients collapsed Hospitals to the point that many surgeries around the world had to be cancelled. Therefore, the aim of this paper is to provide a Machine Learning (ML) model that helps us to prevent when a patient is about to be critical. Although we are in the era of data, regarding the SARS-COV-2 patients, there are currently few tools and solutions that help medical professionals to predict the evolution of patients in order to improve their treatment and the needs of critical resources at hospitals. Moreover, most of these tools have been created from small populations and/or Chinese populations, which carries a high risk of bias. In this paper, we present a model, based on ML techniques, based on 5378 Spanish patients' data from which a quality cohort of 1201 was extracted to train the model. Our model is capable of predicting the probability of death of patients with SARS-COV-2 based on age, sex and comorbidities of the patient. It also allows what-if analysis, with the inclusion of comorbidities that the patient may develop during the SARS-COV-2 infection. For the training of the model, we have followed an agnostic approach. We explored all the active comorbidities during the SARS-COV-2 infection of the patients with the objective that the model weights the effect of each comorbidity on the patient's evolution according to the data available. The model has been validated by using stratified cross-validation with k = 5 to prevent class imbalance. We obtained robust results, presenting a high hit rate, with 84.16% accuracy, 83.33% sensitivity, and an Area Under the Curve (AUC) of 0.871. The main advantage of our model, in addition to its high success rate, is that it can be used with medical records in order to predict their diagnosis, allowing the critical population to be identified in advance. Furthermore, it uses the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD 9-CM) standard. In this sense, we should also emphasize that those hospitals using other encodings can add an intermediate layer business to business (B2B) with the aim of making transformations to the same international format.


Outpatient bowel preparation in children.
A polyethylene glycol electrolyte solution was evaluated as a mechanical bowel preparation prior to surgery in an outpatient setting. Twelve children underwent outpatient bowel preparation (OPBP) prior to a variety of surgical procedures. The technique was well tolerated and consistently produced a well-prepared intestinal tract. This technique will decrease the overall cost of hospitalization, and it enhances patient and parental acceptance of mechanical bowel preparation.


P16INK4a Upregulation Mediated by SIX6 Defines Retinal Ganglion Cell Pathogenesis in Glaucoma.
Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated and progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism of RGC death in glaucoma is still unknown. Here, we demonstrate that the genetic effect of the SIX6 risk variant (rs33912345, His141Asn) is enhanced by another major POAG risk gene, p16INK4a (cyclin-dependent kinase inhibitor 2A, isoform INK4a). We further show that the upregulation of homozygous SIX6 risk alleles (CC) leads to an increase in p16INK4a expression, with subsequent cellular senescence, as evidenced in a mouse model of elevated IOP and in human POAG eyes. Our data indicate that SIX6 and/or IOP promotes POAG by directly increasing p16INK4a expression, leading to RGC senescence in adult human retinas. Our study provides important insights linking genetic susceptibility to the underlying mechanism of RGC death and provides a unified theory of glaucoma pathogenesis.


Effects of molsidomine on the coronary circulation in anesthetized dogs.
The intravenous effects of molsidomine on the coronary circulation, myocardial oxygen consumption, and hemodynamics were investigated in anesthetized, open-chest dogs. Left coronary artery flow was reduced after drug administration, while coronary resistance remained unaffected. The coronary arteriovenous oxygen difference did not change after molsidomine. Myocardial oxygen consumption was significantly reduced. Stroke work of the heart was diminished. Molsidomine caused a dose-dependent decrease in aortic and left ventricular pressures (after-load) as well as a sustained fall in left ventricular end-diastolic and mean pulmonary artery pressures (preload). Heart rate and contractility were only moderately affected. Stroke volume and cardiac output decreased significantly for the experimentation time, while total peripheral resistance increased after 0.25 mg/kg molsidomine. All observed effects of the drug can be explained by extracardiac effects: an increase in venous capacity. No direct effects of molsidomine on myocardial function could be noted. The fall in blood pressure was not induced by vasodilatation of peripheral arteriolar vessels but occurred as sequel of the reduced cardiac output following decreased ventricular filling. Molsidomine improved the oxygen supply-demand balance by decreasing external work of the heart and hence myocardial oxygen demand.


Treatment of low strength complex wastewater using an anaerobic baffled reactor (ABR).
Treatment of a low strength complex wastewater of chemical oxygen demand (COD) around 500mg/L was studied in a 10L capacity laboratory scale anaerobic baffled reactor (ABR). It was operated at hydraulic retention times (HRTs) of 20, 15, 10, 8 and 6h. Corresponding organic loading rates (OLRs) were 0.6, 0.8, 1.2, 1.5 and 2kg COD/m3d. At every HRT (or OLR), pseudo steady state (PSS) was achieved. Even at maximum OLR of 2kg COD/m3d, COD and biochemical oxygen demand (BOD) removals exceeded 88%. Removal of particulate fraction of organics was found to be greater than soluble fraction. Compartment-wise studies of various parameters revealed that if the OLR was larger, the number of initial compartments played significant role in the removal of organics. The values of volatile fatty acids (VFA) demonstrated that hydrolysis and acidogenesis were the main biochemical activities in the initial few compartments. Based on the tracer studies, dead space in the ABR was found to range from 23% to 34%. The flow pattern in the ABR was classified as intermediate between plug flow and perfectly mixed flows. Observations from scanning electron micrographs (SEM) also suggested that distinct phase separation takes place in an ABR. Study of organic and hydraulic shock loads revealed that ABR was capable of sustaining the type of shock loads generally experienced at a sewage treatment plant (STP).


[Issues of France's "Leonetti Act": Involvement of amyotrophic lateral sclerosis patients in prior discussions concerning respiratory support and end-of-life care].
In accordance with the principle of personal autonomy, expert consensus statements on amyotrophic lateral sclerosis (ALS) recommend early engagement with terminal-phase patients on the type of symptomatic treatment to be administered in the event of respiratory failure, since decompensation progresses too rapidly to allow time for a discussion. The French Parliamentary Act on Patients' Rights and End-of-Life Care (dated 22 April 2005) grants individuals the right to refuse unreasonable treatment and obliges physicians to take account of any prior instructions given by a person before he/she became incapable of communicating. The provision of prior instructions is a very reassuring situation for the physician: the autonomous patient indicates his or her choice of end-of-life care. However, there are two pitfalls which must be avoided: (i) holding a discussion for the sole purpose of obtaining prior instructions and (ii) not acknowledging the patient's vulnerability. The present study dealt with 35 ALS patients for whom the question of either intensive care or palliative end-of-life care remained open. Even though the great majority of these individuals were keen to know their exact state of health, 48% refused to consider this circumstance and only 20% expressed prior instructions. These results prompted us to question the ethical dimension of the concept of autonomy beyond its founding formulation: can one envisage an incapacity to confront oneself with the existential question of possible death? In 80% of cases, the physician will have to take a care decision in the absence of any prior instructions from the patient. This amounts to more than respecting a person's autonomy and involves exercising medical responsibility.


Overgrowth after femoral shaft fractures in infants treated with a Pavlik harness.
This study was performed to determine whether overgrowth occurs when treating infantile femoral shaft fractures with a Pavlik harness. Twenty-three patients, aged less than 1 year, treated with a Pavlik harness for a femoral shaft fracture were included. Shortening at the time of injury was recorded on radiographs and compared with those obtained at the follow-up visit 18 months or later. Average overgrowth was 5 mm (1-18 mm). Overgrowth occurs in infants following treatment of femoral fractures with a Pavlik harness. Initial shortening of up to 18 mm was acceptable and resulted in a leg-length discrepancy of less than 5 mm due to overgrowth in our population.


Heparin from intestine and lung source administered in large dose to dogs with acute myocardial ischemia. Similar and dissimilar effects on electrocardiograms and adenosine triphosphate.
Intestinal mucosa heparin (IMH) and beef lung heparin (BLH) were infused into dogs subjected to myocardial ischemia by intermittent coronary artery occlusions. The IMH was from a mixture of beef, sheep, and pig intestinal mucosa. Initial control occlusion and recovery was followed by a second occlusion with 60,000 units of IMH or BLH added. Electrocardiographic S-T segment elevations (ST) were measured acutely. There were no significant differences in ST in non-ischemic myocardium before occlusions or with occlusions. In ischemic myocardium, IMH significantly lowered control ST 84% in amount (t = 6.1 p less than 0.00005), and 76% in number (t = 11.6 p less than 0.00001). BLH lowered control ST a significant, lesser, 36% in amount (t = 3.6 p less than 0.008), and 35% in number (t = 3.2 p less than 0.01). The difference between IMH and BLH in ischemic myocardium was a significant adenosine triphosphate (ATP) levels were assayed after 90 min. ATP levels were 31% higher in both ischemic and non-ischemic myocardium in IMH-treated dogs than in BLH-treated. It was concluded that IMH and BLH are functionally different, and IMH was significantly more effective.


Portuguese adolescents with cystic fibrosis and their parents: An intervention proposal for nursing clinical practice.
Cystic fibrosis is a life-shortening genetic disease. It affects both patient and family with the nurse playing a key role in the monitoring process. This study sought to contribute to enhanced targeted health care to adolescents with cystic fibrosis and their parents by understanding the experiences of living with cystic fibrosis. Based on Afaf Meleis' Transitions Theory (1986) nurses identify the transition experienced by the study participants, thus contributing to the quality of nursing interventions. Two qualitative research studies using data collected through semi-structured interviews were conducted. The Straussian Grounded Theory was applied. The snowball technique was used for recruitment, under the inclusion criteria: adolescents aged between 10 and 21 years; diagnosis of cystic fibrosis for more than one year; and parents of these adolescents. A final sample of 16 adolescents and 14 parents was obtained. Nursing therapeutic interventions acted as a facilitator of the health/illness transition process. Nurses' intervention areas were identified to empower adolescents and their parents with targeted knowledge and abilities to cope with problems. After diagnosis, parents assumed a new role-playing. Adolescents with cystic fibrosis and their parents experience various transition phases. Nurses can better help identifying the onset, persistence and ending of harmful periods. Adolescents with cystic fibrosis and their parents experience various transition phases. Nursing therapeutic interventions are cardinal to the health/illness transition.


Disruption of erythrocyte antioxidant defense system, hematological parameters, induction of pro-inflammatory cytokines and DNA damage in liver of co-exposed rats to aluminium and acrylamide.
The individual toxic effects of aluminium and acrylamide are well known but there are no data on their combined effects. The present study was undertaken to determine (i) hematological parameters during individual and combined chronic exposure to aluminium and acrylamide (ii) correlation of oxidative stress in erythrocytes with pro-inflammatory cytokines expression, DNA damage and histopathological changes in the liver. Rats were exposed to aluminium (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination for 3 weeks. Exposure rats to AlCl3 or/and ACR provoked an increase in MDA, AOPP, H2O2 and a decrease in GSH and NPSH levels in erythrocytes. Activities of catalase, glutathione peroxidase and superoxide dismutase were decreased in all treated rats. Our results showed that all treatments induced an increase in WBC, erythrocyte osmotic fragility and a decrease in RBC, Hb and Ht. While MCV, MCH, MCHC remained unchanged. Hepatic pro-inflammatory cytokines expression including tumor necrosis factor-α, interleukin-6, interleukin-1β was increased suggesting leucocytes infiltration in the liver. A random DNA degradation was observed on agarose gel only in the liver of co-exposed rats to AlCl3 and ACR treatment. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in erythrocytes, pro-inflammatory cytokines and DNA damage in liver.


Surgical ablation of atrial fibrillation is associated with improved survival compared with appendage obliteration alone: An analysis of 100,000 Medicare beneficiaries.
Societal guidelines support the concomitant surgical ablation of atrial fibrillation in patients undergoing cardiac surgery. Recent evidence has highlighted the stroke reduction of left atrial appendage obliteration with or without surgical ablation in similar populations. To inform clinical decision-making, we evaluated real-world outcomes of patients with atrial fibrillation undergoing cardiac surgery by comparing no atrial fibrillation management with left atrial appendage obliteration alone versus surgical ablation + left atrial appendage obliteration. By using the US Centers for Medicare and Medicaid Services inpatient claims database, we evaluated all beneficiaries aged 65 years and older with a diagnosis of atrial fibrillation undergoing coronary artery bypass grafting or mitral/aortic/tricuspid valve repair or replacement between January 2018 and December 2020. Diagnosis-related group and International Classification of Diseases, 10th Revision procedure codes were used to define variables. Risk adjustment was performed with regression analysis using inverse probability weighting of propensity scores and Cox proportional hazards models. Subgroup analyses stratified patients by primary operation and paroxysmal or persistent atrial fibrillation. A total of 103,382 patients with preoperative atrial fibrillation were stratified by surgical ablation + left atrial appendage obliteration (10,437; 10.1%), left atrial appendage obliteration alone (12,901; 12.5%), or no atrial fibrillation management (80,044; 77.4%). Patients with persistent atrial fibrillation (21,076; 20.4%) received the highest proportion of surgical ablation + left atrial appendage obliteration (4661 19.4%) and left atrial appendage obliteration alone (3%724%; 15.4%) versus no atrial fibrillation management (15,688; 65.2%). Likewise, patients undergoing open atrial operations (mitral/tricuspid; 17,204; 16.6%) had higher proportions of atrial fibrillation treatment (surgical ablation + left atrial appendage obliteration 5267 30.6%; left atrial appendage obliteration alone 4259 24.8%; no atrial fibrillation management 7678 44.6%). After robust risk adjustment, surgical ablation + left atrial appendage obliteration was independently associated with reduced 3-year mortality compared with no atrial fibrillation treatment (hazard ratio, 0.68, P < .001) and left atrial appendage obliteration alone (hazard ratio, 0.90, P < .001). Compared with no atrial fibrillation treatment, readmissions for embolic stroke were lower with both surgical ablation + left atrial appendage obliteration (hazard ratio, 0.77, P = .009) and left atrial appendage obliteration alone (hazard ratio, 0.73, P < .001). Reduction in 3-year composite mortality or stroke after surgical ablation + left atrial appendage obliteration was superior to left atrial appendage alone (hazard ratio, 0.90, P = .035). In Medicare beneficiaries with atrial fibrillation undergoing cardiac surgery, the surgical management of atrial fibrillation was associated with lower 3-year mortality and readmission for stroke, with surgical ablation + left atrial appendage obliteration being associated with higher survival compared with left atrial appendage obliteration alone.


A History of Development of Medical Missions and Catholic Evangelization in Sub-Saharan Africa From the Early Twentieth Century to the Present: Tracing Some Representative Founders and Orders in the Context of the Twentieth Century Church.
Although the care of the sick has been a charism of Catholic community since the beginning, and hospitals as we know them have developed since the fourth century, religious orders began to develop hospitals as part of their mission work during the colonial expansion of the seventeenth century. These early efforts, however, were primarily a response to the needs of the colonists as well as recognition that the poor who were sick required care in these regions. It can be argued that medical missions developed during the twentieth century as a response to the outreach of Protestants as well as the exposure of physicians to the needs in mission territories, and that their advancement and success impacted the attitudes of the popes and bishops of the twentieth century. This article examines several individuals and organizations who have contributed to the development of medical missions in Africa in modern times and trace the approach of the Church toward medical missions by exploring missionary religious orders, especially women's religious orders, and papal and council documents. It primarily considers the role of medical missions in areas that had only a limited Catholic presence prior to nineteenth and twentieth centuries, and where Catholic health care and the local Catholic Church essentially developed together, and considers ways in which the growth of medical missions and the thinking of the Church developed together.


A combined approach of variance-reduction techniques for the efficient Monte Carlo simulation of linacs.
A method based on a combination of the variance-reduction techniques of particle splitting and Russian roulette is presented. This method improves the efficiency of radiation transport through linear accelerator geometries simulated with the Monte Carlo method. The method named as 'splitting-roulette' was implemented on the Monte Carlo code [Formula: see text] and tested on an Elekta linac, although it is general enough to be implemented on any other general-purpose Monte Carlo radiation transport code and linac geometry. Splitting-roulette uses any of the following two modes of splitting: simple splitting and 'selective splitting'. Selective splitting is a new splitting mode based on the angular distribution of bremsstrahlung photons implemented in the Monte Carlo code [Formula: see text]. Splitting-roulette improves the simulation efficiency of an Elekta SL25 linac by a factor of 45.


Mental Distress and Professional Commitment among Chinese Medical Postgraduate Students: A Moderated Mediation of Psychological Capital and the Supervisor-Postgraduate Relationship.
This study determined the relationship between mental distress and professional commitment among medical postgraduate students, and the roles of psychological capital as a mediator and the supervisor-postgraduate relationship as a moderator. This cross-sectional study recruited 836 medical postgraduate students from eight medical universities and the medical college of comprehensive universities in Guangdong Province, China. Participants were assessed through questionnaires, which covered demographic items, the supervisor-postgraduate relationship scale, the psychological capital questionnaire, the symptom checklist - 90 (SCL -90), and the professional commitment scale. We used descriptive statistics to describe demographics and mental distress and professional commitment scores. Pearson's analysis was used to identify correlations between the variables and the SPSS PROCESS macro was performed to confirm mediating and moderating effects of psychological capital and the supervisor-postgraduate relationship. Mental distress was negatively related with professional commitment (r = -0.262, p < 0.01) and psychological capital (r = -0.442, p < 0.01). Psychological capital was positively associated with professional commitment (r = 0.486, p < 0.01). The confidence interval (CI) suggested that psychological capital mediated the relationship between mental distress and professional commitment (95% CI, -0.198 to - 0.143), and the supervisor-postgraduate relationship had a moderate role between psychological capital and professional commitment (95% CI, 0.069 to -0.212). Hence, educators may refer to these findings to improve professional commitment level among medical postgraduate students.


Synthesis, antimicrobial evaluation and QSAR studies of p-hydroxy benzoic acid derivatives.
In the present study, a series of p-hydroxy benzoic acid derivatives (1-29) was synthesized and tested for its antimicrobial potential. Results of antimicrobial studies indicated that in general, Schiff bases were found to be more active as compared to esters and compound 14 was found to be most potent antimicrobial agent (pMICam=1.50 µM/ml). QSAR study was performed in order to understand the relationship between antimicrobial activity and changes in the molecular structures which indicated that antimicrobial activity of the synthesized compounds was governed by valence first order molecular connectivity index (1χv), Kier's alpha first order shape index (κα1), Kier's first order shape index (κ1) and Balaban topological index (J).


Troponin I phosphorylation plays an important role in the relaxant effect of beta-adrenergic stimulation in mouse hearts.
The present study was designed to address the question of the contribution of cardiac troponin I (cTnI) phosphorylation to the enhanced rate of relaxation during beta-adrenergic stimulation in hearts in situ. In situ hemodynamic measurements were performed in mouse hearts that (1) express normal level of phospholamban (PLB) and either express cTnI (PLB/cTnI) or the slow skeletal isoform of TnI (PLB/ssTnI) that cannot be phosphorylated by protein kinase A (PKA) or (2) do not express PLB and either express cTnI (PLBKO/cTnI) or ssTnI (PLBKO/ssTnI). In the basal state, there was no difference in heart rate (HR), developed pressure (DP), left ventricular end-diastolic pressure (LVEDP) or rate of contraction (+dP/dt) between PLB/cTnI and PLB/ssTnI groups. However, hearts expressing ssTnI (PLB/ssTnI) showed a significantly decreased rate of relaxation (-dP/dt) when compared with hearts expressing cTnI (PLB/cTnI). In response to beta-adrenergic agonist, isoproterenol (ISO), HR increased similarly in both groups. At the two highest doses of ISO, the rate of relaxation (-dP/dt) was significantly smaller in PLB/ssTnI than in PLB/cTnI hearts. In the basal state, there was no difference in HR, DP, LVEDP,+dP/dt and -dP/dt between PLBKO/cTnI and PLBKO/ssTnI hearts. In response to ISO, HR increased similarly in both groups and was only slightly smaller in PLBKO/ssTnI group at the lowest dose of ISO. However, during ISO perfusion, when cTnI was phosphorylated, the rate of relaxation was significantly slower in PLBKO/ssTnI compared to PLBKO/cTnI hearts. Our data support the hypothesis that phosphorylation of cTnI significantly contributes to the enhanced rate of relaxation during beta-adrenergic stimulation.


Short-term outcomes following total minimally invasive oesophagectomy.
Minimally invasive oesophagectomy (MIO; thoracoscopy, laparoscopy, cervical anastomosis) is a complex procedure and few substantial series have been published. This study documented the morbidity, mortality and challenges of adopting MIO in a specialist unit in the UK. A prospective group of 77 patients was listed consecutively with the intention of performing MIO. Three other patients underwent open oesophagectomy during the study period. MIO was attempted in 77 patients, completed successfully in 70, abandoned in six patients (8 per cent) with unsuspected metastatic disease, and converted to a thoracoscopic anastomosis in one patient. There was one in-hospital death (1 per cent). Complications occurred in 33 patients (47 per cent), including nine gastric conduit-related complications (13 per cent). Median lymph node harvest was 21 (range 7-48) nodes. Mean overall and disease-free survival times were 35 and 33 months respectively. Median disease-free survival for patients with stage III disease was 26 months. MIO can be performed with acceptable mortality and morbidity rates in an unselected series of patients. There was more morbidity related to gastric tube ischaemia than was expected.


Electrophysiological correlates of visual categorization: evidence for cognitive dysfunctions in early Parkinson's disease.
Our aim was to examine the electrophysiological correlates of perceptual categorization in Parkinson's disease (PD). We recorded visual event-related potentials (ERPs) in a natural scene categorization task in drug naive idiopathic PD patients and healthy control subjects. In the control group, there was a significant early difference (150-250 ms poststimulus) between ERPs elicited by pictures containing animals and scenes without animals. In spite of relatively preserved basic-level visual functions, this was not observable in the PD group. These results raise the possibility for striatal contributions to visual categorization and may provide a novel protocol for further clinical studies.


The pharmacology of new ethylenediamine derivatives (ROM-126, ROM-131, MK-142) with antiarrhythmic action. Part I. General pharmacological properties.
Mentioned compounds, studied on several species of animals, decrease blood pressure and the heart rate, modify catecholamine-induced effects, show properties characteristic for the beta-receptor blocking agents. The stated differences being due mainly to the power of their action. These compounds possess also spasmolytic and locally anaesthetic action of various degrees. Only ROM-131 has antihistamine action.


The activity of an esterified cholesterol transferring factor in human and rat serum.
In incubations containing mixtures of lipoproteins isolated either from humans or from rats, the addition of human lipoproteins-free serum (the dialysed 1.25 g/ml infranatant solution) was more than five times more effective than that of the rat in promoting the transfer of esterified [3H]cholesterol from high density lipoproteins to very low density lipoproteins, regardless of the species origin of the lipoproteins, implying the existence of an esterified cholesterol transferring factor of much greater activity in human than in rat serum.


P(3)G - 10 years of toolbuilding: From the population biobank to the clinic.
Over the past ten years, the Public Population Project in Genomics and Society ("P(3)G") has grown as a consortium. It has expanded its range of services and resources to adapt to the ever-evolving needs of the research community. From its outset - when P(3)G first tackled the building of biobanks as resources as well as data cataloguing and harmonization for data integration - to its new mission and vision, it has continually developed the tools for the conceptualization and design of population biobanks from their inception to their use to their closure. In so doing, P(3)G has become key in fostering research infrastructures to facilitate transition to the clinic. The consortium has become a crucial stakeholder in the international scientific, ethical, legal, and social research communities.


An analysis of patient motivation for seeking online treatment for binge eating disorder-A mixed methods study combining systematic text condensation with sentiment analysis.
Online treatment for binge eating disorder (BED) is an easily available option for treatment compared to most standard treatment procedures. However, little is known about how motivation types characterize this population and how these impact treatment adherence and effect in an online setting. Therefore, we aimed to investigate a sample of written motivation statements from BED patients, to learn more about how treatment and online treatment in particular, presents in this population. Using self-determination theory in a mixed methods context, we investigated which types of motivation were prevalent in our sample, how this was connected with patient sentiment, and how these constructs influence treatment and adherence. Contrary to what most current literature suggests, we found that in our sample (n = 148), motivation type was not connected with treatment outcome. We did find a strong association between sentiment scores and motivation types, indicating the model is apt at detecting effects. We found that when comparing an adult and young adult population, they did not differ in motivation type and the treatment was equally effective in young adults and adults. In the sentiment scores there was a difference between sentiment score and adherence in the young adult group, as the more positive the young adults were, the less likely they were to complete the program. Because motivation type does not influence online treatment to the same degree as it would in face-to-face treatment it indicates that the typical barriers to treatment may be less crucial in an online setting. This should be considered during intake; as less motivated patients may be able to adhere better to online treatment, because the latter imposes fewer barriers of the kind that only strong motivation can overcome. The fact that motivation type and sentiment score of the written texts are strongly associated, indicate a potential for automated models to detect motivation based on sentiment.


The Cre-loxP recombination-based reporter system for plant transcriptional expression studies.
To facilitate the characterization of plant genes, the Cre-loxP site-specific recombination system was adapted to make reporter vectors for plant expression studies. This system allows promoter fragments to be cloned into a small vector (univector) and subsequently recombined in vitro with binary vectors containing different reporter genes precisely at near-perfect efficiency. We have constructed univector-adapted vectors with three reporters, beta-glucuronidase, luciferase, and green fluorescent protein, and a BASTA-resistance gene for selection of plant transformants. Expression in plants using the new system was validated by comparison to conventional reporter vectors. These new vectors are efficient and economical alternatives to the other plant reporter vectors currently available. The royalty-free Cre-loxP system serves as a platform for the future expansion of recombination-based cloning vectors for plant research.


Transdifferentiation versus stem cell hypothesis for the regeneration of islet beta-cells in the pancreas.
The pancreas is composed of at least three types of differentiated tissue: the hormone-containing cells in islets (4 different cell types), the exocrine zymogen-containing acini, and the centroacinar cells, ductules and ducts (ductal tree). All of these cells appear to have a common origin during embryogenesis in the form of duct-like protodifferentiated cells. Later in life, the acinar and ductal cells retain a significant proliferative capacity that can ensure cell renewal and growth, whereas the islet cells become mitotically inactive. Interestingly, new islet cells, including the insulin-producing beta-cells, can regenerate after tissue injury by a process called neogenesis. The neogenetic process involves differentiation of duct-like (exocrine) epithelial cells to hormone-expressing cells. In this paper, we review the question whether islet beta-cell regeneration or neogenesis in the pancreas depends on "embryonic-like" stem cells or on transdifferentiation of "fully differentiated" cells. This issue is important to find the right model for in vitro research aiming at controlling the process of beta-cell neogenesis. The latter could lead to applications in the treatment of diabetes where functional beta-cells are deficient. We conclude from the available evidence that there is as yet no evidence for the existence of "dormant" stem cells in the adult pancreas. There is some evidence, however, that differentiated exocrine acinar and/or duct cells retain the capacity to transdifferentiate into insulin-expressing beta-cells.


Hydrothermally stable ordered mesoporous titanosilicates with highly active catalytic sites.
Mesoporous titanosilicates (MTS-9) are successfully prepared in strong acidic media by a two-step synthesis. MTS-9 has an ordered hexagonal structure and exhibits superior hydrothermal stability and high catalytic activity for the oxidation of the small molecules of phenol and styrene and also of the bulky molecule of trimethylphenol.


A randomized controlled trial of the Cool Teens CD-ROM computerized program for adolescent anxiety.
Computerized cognitive behavioral interventions for anxiety disorders in adults have been shown to be efficacious, but limited data are available on the use of computerized interventions with young persons. Adolescents in particular are difficult to engage in treatment and may be especially suited to computerized technologies. This paper describes the results of a small randomized controlled trial of the Cool Teens program for adolescent anxiety, and examines potential barriers to treatment and user preferences of computerized technology in this population. Forty-three adolescents with a primary diagnosis of anxiety were randomly allocated to the Cool Teens program, a 12-week computerized cognitive-behavioral therapy program for anxiety management, or a 12-week wait list. Effects on symptoms, negative thoughts, and life interference were assessed at post-treatment and 3-month follow-up, based on diagnosis as well as self and maternal report. Using mixed-model analyses, at post-treatment and follow-up assessments, adolescents in the Cool Teens condition, compared with those on the wait list, were found to have significant reductions in the total number of anxiety disorders, the severity of the primary anxiety disorder, and the average severity for all disorders. These results were matched by significant reductions in mother and child questionnaire reports of anxiety, internalizing symptoms, automatic thoughts, and life interference. Further few barriers to treatment were found, and user preferences indicated that the computerized treatment was well suited to adolescents with anxiety. The Cool Teens program is efficacious for treatment of adolescent anxiety. Clinical trial registration information-A randomized controlled trial of the Cool Teens computerized program for anxious adolescents compared with waist list; http://www.anzctr.org.au; ACTRN12611000508976.


A case of tracheal obstruction caused by reflux and aspiration of semi-solid nutrients via the nasogastric tube.
Semi-solid nutrients have several advantages, including reduced cases of diarrhea and aspiration pneumonia, and are usually administered via percutaneous endoscopic gastrostomy owing to its high viscosity. Administering semi-solid nutrients via a nasogastric tube was recently introduced in clinical practice; however, its safety has not been well confirmed. An 82-year-old man with a right occipital hemorrhage and severe diarrhea consulted the nutritional support team. Administrations of semi-solid nutrients (HINE E-GEL®) via the nasogastric tube was initiated, which gradually alleviated his symptoms. Fourteen days after initiation, he suddenly had pulmonary failure owing to a tracheal obstruction caused by the reflux and aspiration of semi-solid nutrients. Intubation and subsequent reflex cough expectorated sputum with gel-form particles, which quickly stabilized his pulmonary condition. After this, his hospital course was stable, and he was referred to another hospital for further rehabilitation. Semi-solid nutrients administered via the nasogastric tube have different ingredients compared with those administered via percutaneous endoscopic gastrostomy. HINE E-GEL®, for example, contains pectin and calcium phosphate that changes from liquid to semi-solid inside the stomach via chemical reactions under acidic conditions. Data on the viscosity of HINE E-GEL® in vivo are insufficient. Uncertainty regarding the form and viscosity of HINE E-GEL® inside the stomach complicates clinical practice. Although semi-solid nutrients have several advantages, including reduced diarrhea and gastroesophageal reflux, evidence on semi-solid nutrients via the nasogastric tube is insufficient. It should be noted that semi-solid nutrient reflux can be more fatal than liquid nutrients.


Pushing the Limit of Open-Circuit Voltage Deficit via Modifying Buried Interface in CsPbI3 Perovskite Solar Cells.
Although CsPbI3 perovskites have shown tremendous potential in the photovoltaic field owing to their excellent thermal stability, the device performance is seriously restricted by severe photovoltage loss. The buried titanium oxide/perovskite interface plays a critical role in interfacial charge transport and perovskite crystallization, which is closely related to open-circuit voltage deficit stemming from nonradiative recombination. Herein, target molecules named 3-sulphonatopropyl acrylate potassium salts are deliberately employed with special functional groups for modifying the buried interface, giving rise to favorable functions in terms of passivating interfacial defects, optimizing energetic alignment, and facilitating perovskite crystallization. Experimental characterizations and theoretical calculations reveal that the buried interface modification inhibits the electron transfer barrier and simultaneously improves perovskite crystal quality, thereby reducing trap-assisted charge recombination and interfacial energetic loss. Consequently, the omnibearing modification regarding the buried interface endows the devices with an impressive efficiency of 20.98%, achieving a record-low VOC deficit of 0.451 V. The as-proposed buried interface modification strategy renders with a universal prescription to push the limit of VOC deficit, showing a promising future in developing high-performance all-inorganic perovskite photovoltaics.


Accelerated chemistry in the reaction between the hydroxyl radical and methanol at interstellar temperatures facilitated by tunnelling.
Understanding the abundances of molecules in dense interstellar clouds requires knowledge of the rates of gas-phase reactions between uncharged species. However, because of the low temperatures within these clouds, reactions with an activation barrier were considered too slow to play an important role. Here we show that, despite the presence of a barrier, the rate coefficient for the reaction between the hydroxyl radical (OH) and methanol--one of the most abundant organic molecules in space--is almost two orders of magnitude larger at 63 K than previously measured at ∼200 K. We also observe the formation of the methoxy radical product, which was recently detected in space. These results are interpreted by the formation of a hydrogen-bonded complex that is sufficiently long-lived to undergo quantum-mechanical tunnelling to form products. We postulate that this tunnelling mechanism for the oxidation of organic molecules by OH is widespread in low-temperature interstellar environments.


Patient safety in the rehabilitation of the adult with a spinal cord injury.
There are approximately 12,000 new cases of traumatic spinal cord injury (SCI) annually. In 2010, there were approximately 265,000 individuals living with SCI. Over time, the average age of people with SCI has steadily risen, and it is now 40.7 years. There are multiple medical complications that are commonly seen in individuals with SCI. These include, but are not exclusively limited to, pneumonia, decubiti ulcers, undiagnosed fractures, urinary tract infections, autonomic dysreflexia, deep venous thrombosis, and pulmonary embolism. This article addresses the issue of patient safety in the care of adults living with an SCI.


Blood-brain barrier permeability and brain concentration of sodium, potassium, and chloride during focal ischemia.
Brain edema formation during the early stages of focal cerebral ischemia is associated with an increase in both sodium content and blood-brain barrier (BBB) sodium transport. The goals of this study were to determine whether chloride is the principal anion that accumulates in ischemic brain, how the rate of BBB transport of chloride compares with its rate of accumulation, and whether the stimulation seen in BBB sodium transport is also seen with other cations. Focal ischemia was produced by occlusion of the middle cerebral artery (MCAO) in anesthetized rats. Over the first 6 h after MCAO, the amount of brain water in the center of the ischemic cortex increased progressively at a rate of 0.15 +/- 0.02 (SE) g/g dry wt/h. This was accompanied by a net increase in brain sodium (48 +/- 12 mumol/g dry wt/h) and a loss of potassium (34 +/- 7 mumol/g dry wt/h). The net rate of chloride accumulation (16 +/- 1 mumol/g dry wt/h) approximated the net rate of increase of cations. Three hours after MCAO, the BBB permeability to three ions (22Na, 36Cl, and 86Rb) and two passive permeability tracers ([3H]alpha-aminoisobutyric acid ([3H]AIB) and [14C]urea) was determined. Permeability to either passive tracer was not increased, indicating that the BBB was intact. The rate of 36Cl influx was 3 times greater and the rate of 22Na influx 1.8 times greater than their respective net rates of accumulation in ischemic brain.(ABSTRACT TRUNCATED AT 250 WORDS)


Leptospirosis in an urban setting: case report and review of an emerging infectious disease.
Leptospiosis is a common zoonosis affecting most mammals. Leptospirosis has protean manifestations ranging from a flu-like illness to fulminant hepatic and renal failure culminating in death. Although the diagnosis is often not considered upon presentation, the literature suggests that leptospirosis is a reemerging infectious disease in urban centers throughout the industrialized world. It will be incumbent upon Emergency Physicians to include this spirochetal disease in the differential diagnosis of febrile patients with appropriate risk factors and symptomatology. We present the case of a 36 year-old woman who presented to the Emergency Department with fever and hypotension. We review the literature on leptospirosis with specific focus on risk factors and pathogenesis, clinical manifestations, diagnosis, treatment, and outcome.


Prenatal Learning and Memory: Review on the Impact of Exposure.
Prenatal Learning is a topic still debated for its existence, although the concept is well known since ancient times. The present review highlights the impact of various stimuli on learning and memory in prenatal and postnatal life. For review, various articles from preclinical and clinical studies providing early pieces of evidence of prenatal learning to date were included based on the relevancy of the databases, namely, Scopus, Pubmed, and Google Scholar. Learning is the process of acquiring skills/ preferences/ habits from the experiences of the exposures of the past. These exposures are the stimuli, which help in categorizing learning into associated or nonassociated learning. The stimuli of adults related to auditory, gustatory, olfactory, visual, touch, etc. are also accessible to the prenatal life in utero either directly or indirectly through the mother. The effects of these stimuli are remarkable during prenatal life and can be seen clearly in infants. These stimuli play an important role in prenatal learning and contribute to neuronal development. The present review summarizes the pieces of evidence for each of these types of learning & their impact on the ex utero life, a futuristic view & the scope of understanding prenatal learning. The review also elucidates the factors affecting prenatal learning. Studies from clinical and preclinical studies reflected the impacts of several aspects of an infant's life and the memory created during prenatal life was found to be most likely carried on to postnatal life.


Local and systemic immunosuppression in pancreatic cancer: Targeting the stalwarts in tumor's arsenal.
Late detection, compromised immune system, and chemotherapy resistance underlie the poor patient prognosis for pancreatic ductal adenocarcinoma (PDAC) patients, making it the 3rd leading cause of cancer-related deaths in the United States. Cooperation between the tumor cells and the immune system leads to the immune escape and eventual establishment of the tumor. For more than 20 years, sincere efforts have been made to intercept the tumor-immune crosstalk and identify the probable therapeutic targets for breaking self-tolerance toward tumor antigens. However, the success of these studies depends on detailed examination and understanding of tumor-immune cell interactions, not only in the primary tumor but also at distant systemic niches. Innate and adaptive arms of the immune system sculpt tumor immunogenicity, where they not only aid in providing an amenable environment for their survival but also act as a driver for tumor relapse at primary or distant organ sites. This review article highlights the key events associated with tumor-immune communication and associated immunosuppression at both local and systemic microenvironments in PDAC. Furthermore, we discuss the approaches and benefits of targeting both local and systemic immunosuppression for PDAC patients. The present articles integrate data from clinical and genetic mouse model studies to provide a widespread consensus on the role of local and systemic immunosuppression in undermining the anti-tumor immune responses against PDAC.


Neuroradiologic findings of brain lesions related to exanthema subitum.
The neuroradiologic findings of the brain lesions in eight infants with exanthema subitum were normal in three, suspected vascular lesions in two, and symmetric thalamic lesions with or without diffuse brain edema in the other three. In addition, diffuse brain edema or focal cerebral lesions were observed in 13 previously reported Japanese infants. These findings suggest that the pathogeneses of the brain lesions related to exanthema subitum are variable.


High-risk behaviors while driving: A population-based study from Iran.
Traffic injuries are becoming one of the most important challenges of public health systems. Because these injuries are mostly preventable, the aim of this study is to evaluate the four main high-risk behaviors while driving. This cross-sectional study was conducted on a random sample from the population of Mashhad, Iran, in 2014. A checklist and a previously validated questionnaire for the transtheoretical stages of change model (TTM) were used for data collection. Statistical analyses were performed using SPSS 11.5 software with P <.05 statistically significant. Totally 431 individuals were included with a mean age of 30 ± 11.3 years. Forty-three percent (183) were male. The TTM model revealed that participants were mostly in pre-actional phases regarding not using a cell phone while driving (80%), fastening the driver's seat belt (66%), front seat belt (68%), and rear seat belt (85%) The penalty was a protective factor only for using cellphone (odd ratio [OR] = 0.82, 95% confidence interval [CI], 0.68-0.98). Lower education (OR = 0.12, 95% CI, 0.01-0.94) and male gender (OR = 0.35, 95% CI, 0.14-0.83) were indicative of lower rates of fastening the front and rear seat belts. The stages of change model among study participants is a proper reflection of the effectiveness of the current policies. More serious actions regarding these high-risk behaviors should be considered in legislation.


Establishment of highly specific and quantitative immunoassay systems for staphylococcal enterotoxin A, B, and C using newly-developed monoclonal antibodies.
Staphylococcal enterotoxin (SE) activities remain after boiling or treating with proteases. The main symptoms such as vomiting and diarrhea, are caused by the ingestion of SEs. Among SEs, SEA has been reported to be the major and most toxic protein. A highly specific and simple assay system is required to diagnose staphylococcal food poisoning. Therefore, the development of a suitable assay system is strongly anticipated. In this study, we have established a highly specific and sensitive avidin-biotin sandwich ELISA (ABS-ELISA) system for SEA, SEB, and SEC1 using newly-developed monoclonal antibodies. The linearity of these systems obtained was in the range of 0.78-25 ng/ml for each SE, and furthermore, the lower concentrations of SEs could also be detected. The recoveries of SEs from murine serum, skim milk solution, and raw milk were found to be over 90%, suggesting that our systems could detect SEs without any interventions, such as these from milk or serum proteins. We were also able to quantify SEs in 22 specimens of culture supernatants of S. aureus isolated in past occurrences. Our established system should be very useful not only in the clinical field but also in various fields of investigation because of its quantifi-cation and simplicity in detecting SEs.


Histopathological, immunohistochemical and molecular cytogenetic analysis of 21 spindle cell/sclerosing rhabdomyosarcomas.
Recently, spindle cell/sclerosing rhabdomyosarcoma (RMS) has been recognized as another distinct variant of a RMS. We evaluated clinicopathological features of 21 cases of spindle cell and sclerosing RMS and performed fluorescent in situ hybridization (FISH) testing in 10 (47.6%) tumours. Twenty-one tumours occurred in 16 males and 5 females (mean age, 19.7 years); commonly in the head and neck region (8) (38%) and extremities (7) (33.3%), followed by paratesticular region (2) (9.5%), chest wall (1), abdomen (1), pelvis (1) and paraspinal region (1). Average tumour size was 7.9 cm. Histopathologically, tumours that were spindle cell type (8) (38%) mostly occurred in the head and neck region, while sclerosing type (10) (47.6%) mostly occurred in the extremities. Remaining three (14.2%) tumours were mixed (sclerosing with spindle cell type). Tumour areas resembling embryonal RMS (ERMS) and alveolar RMS (ARMS) were noted in eight and three tumours respectively. Immunohistochemically, tumour cells were positive for desmin (21/21) (100%), MyoD1 (19/19) (100%), myogenin (13/15) (86.6%), SMA (2/3) and MIC2 (1/8) (12.5%). On FISH testing, none of the 10 tumours exhibited RMS1 (PAX3-FOXO1) or RMS 2 (PAX7-FOXO1) fusion. Eighteen patients underwent surgical resection and were offered adjuvant chemotherapy (CT) (4 cases), adjuvant CT + radiotherapy (RT) (4 cases) and adjuvant RT (1 case). Two patients underwent CT and a single patient received CT + RT. On follow-up (16 cases) (2-36 months), six tumours recurred and nine metastasized. Spindle/sclerosing RMSs are aggressive tumours and occur commonly in the head and neck and extremity sites. These tumours are histopathologically interrelated. Their immunohistochemical and cytogenetic profile is closer to ERMS than ARMS.


Extracellular circular RNA profiles in plasma and urine of healthy, male college athletes.
Circular RNA (circRNA) are a recently discovered class of RNA characterized by a covalently-bonded back-splice junction. As circRNAs are inherently more stable than other RNA species, they may be detected extracellularly in peripheral biofluids and provide novel biomarkers. While circRNA have been identified previously in peripheral biofluids, there are few datasets for circRNA junctions from healthy controls. We collected 134 plasma and 114 urine samples from 54 healthy, male college athlete volunteers, and used RNASeq to determine circRNA content. The intersection of six bioinformatic tools identified 965 high-confidence, characteristic circRNA junctions in plasma and 72 in urine. Highly-expressed circRNA junctions were validated by qRT-PCR. Longitudinal samples were collected from a subset, demonstrating circRNA expression was stable over time. Lastly, the ratio of circular to linear transcripts was higher in plasma than urine. This study provides a valuable resource for characterization of circRNA in plasma and urine from healthy volunteers, one that can be developed and reassessed as researchers probe the circRNA contents of biofluids across physiological changes and disease states.


Effect of ytterbium amount on LaNbO4:Tm3+,Yb3+ nanoparticles for bio-labelling applications.
This work investigates how Yb3+ concentration affects the luminescent properties of LaNbO4 nanoparticles for medical imaging applications. Due to the highly transparent optical window for organic tissues in the near infrared region (650-1000 nm), upconversion fluorescence allows near infrared wavelengths to penetrate deeply into tissues, which is useful in biomedical areas such as biodetection, activated phototherapy, and screening. Upconversion nanoparticles based on LaNbO4 doped with Tm3+ and Yb3+ were prepared by the one-step industrial process called Spray Pyrolysis. Samples with different Tm3+:Yb3+ molar ratios (1:4, 1:8 and 1:16) were obtained. The X-ray powder diffractograms of all the samples displayed the typical peaks of a crystalline material (tetragonal phase). Emission bands emerged in the blue, red, and near infrared regions, and they corresponded to the Tm3+1G4 → 3H6 (475 nm), 1G4 → 3F4 (650 nm), 3F2,3 → 3H6 (690 nm), and 3H4 → 3H6 (803 nm) transitions, which indicated a two-photon absorption process. As for bio-labelling application, the results indicated that Yb3+ concentration was directly related to signal intensity. The intensity of positive conversion emissions depends directly on Yb3+ concentration. The bio-labelling tests pointed to the potential application of these materials. The sample containing the highest amount of Yb3+ provided better results and was easier to detect than the standard sample.


Sonographic classification of testicular tumors by tissue harmonic imaging: experience of 58 cases.
To evaluate the relationship between our proposed sonographic classification of testicular tumors by tissue harmonic imaging and histological type. We retrospectively analyzed 58 testicular tumors and tumor-like lesions [seminomatous germ cell tumor (SGCT): 28; non-seminomatous germ cell tumor (NSGCT): 16; lymphoid and hematopoietic tumor (LHT): 7; Leydig cell tumor: 1; epidermal cyst: 2; and tumor of paratesticular structure (TPS): 4]. We divided a sonographic image into six types for morphological criteria and three types for color Doppler criteria. We examined the relationship between the sonographic classification and histological type. For morphological criteria, there were 21 cases of Type I (36%), 15 Type II (26%), 9 Type III (15%), five Type IV (9%), five Type V (9%), and three Type VI (5%). For color Doppler criteria, there were 47 cases classified as hypervascular (81%), eight as hypovascular (14%), and three as avascular (5%). Most of the SGCTs were divided into types I and II; the NSGCTs into types III, IV, and V; the LHTs into only type II; and the TPSs into type VI. We established a sonographic classification of testicular tumors with various histological types. This sonographic classification is potentially useful for estimating the histological type of testicular tumors.


Antigenic structure of adenylate kinase from porcine skeletal muscle--II. Immunochemical cross-reactivity of fragments from adenylate kinase.
Specific antibody to a fragment [CBb(2-56)] of porcine muscle adenylate kinase was purified from goat antiserum against adenylate kinase on an immunoadsorbent column. This anti-CBb antibody cross-reacted in solid phase radioimmunoassay with two other CNBr-fragments of adenylate kinase, CBfN(81-125) and CBfC(126-194). This cross-reactivity explained their high inhibition activities in quantitative precipitin reaction between adenylate kinase and goat antiserum shown in the previous work. Cysteinyl residues of the enzyme (positions 25 and 187) were S-cyanylated with 2-nitro-5-thiocyanobenzoic acid and the enzyme was cleaved at these residues. Fragment 1-24 thus obtained was purified. The fragment 1-24, composing the N-terminal half of CBb(2-56), accounted for full activity of CBb to anti-CBb in radioimmunoassay. Hence antigenic region(s) of CBb(2-56) exist in its N-terminal half, 2-24, and this determinant(s) may be closely related to the cross-reactivity among CB-fragments. CBfN also bound to the antibody fraction which had not been adsorbed to CBb-Sepharose (non-anti-CBb). CBfN carried additional antigenic regions. In conclusion, we propose that the antigenic reactive region(s) of adenylate kinase responsible for the cross-reactivity of the CB-fragments are as follows: -Glu-Glu-Lys-Leu-Lys-Lys- (2-7), -Glu-Glu-Phe-Lys-Arg-Lys- (103-108), -Glu-Glu-Thr-Ile-Lys-Lys- (143-148).


Immunoregulation in cancer-associated cachexia.
Cancer-associated cachexia is a multi-organ disorder associated with progressive weight loss due to a variable combination of anorexia, systemic inflammation and excessive energy wasting. Considering the importance of immunoregulation in cachexia, it still lacks a complete understanding of the immunological mechanisms in cachectic progression. Our aim here is to describe the complex immunoregulatory system in cachexia. We summarize the effects and translational potential of the immune system on the development of cancer-associated cachexia and we attempt to conclude with thoughts on precise and integrated therapeutic strategies under the complex immunological context of cachexia. This review is focused on three main key concepts. First, we highlight the inflammatory factors and additional mediators that have been identified to modulate this syndrome. Second, we decipher the potential role of immune checkpoints in tissue wasting. Third, we discuss the multilayered insights in cachexia through the immunometabolic axis, immune-gut axis and immune-nerve axis.


Surgery for gastric cancer: 10-year experience worldwide.
To demonstrate recent experience of gastric cancer surgery worldwide and to evaluate modern strategies for the treatment of gastric cancer, we investigated the English-language literature of the past 10 years, based on papers published in well-known medical journals. In many countries, the increased detection of early gastric cancer, advanced operative procedures, and careful postoperative management have improved the surgical results of gastric cancer over the years. Although randomized controlled trials in Europe showed no survival benefit of D2 resection over D1 resection, the results must be interpreted with caution and cannot be extrapolated to Japanese patients, because the morbidity and mortality after D2 gastrectomy in Japan are much less than those after D1 gastrectomy in Europe. Recently, less invasive treatments, including endoscopic mucosal resection and laparoscopic gastrectomy, have become feasible for patients with early gastric cancer, but their risks and benefits compared with traditional gastrectomy are unclear.


Resonance Raman study on yeast cytochrome c peroxidase. Effect of coordination and axial ligands.
Resonance Raman spectra are reported for native ferric cytochrome c peroxidase, its cyanide and fluoride compounds, those of the ferrous enzyme and its cyanide and carbonyl compounds, and the spectrum of the hydrogen peroxide compound, compound I. Band frequencies of ferric horseradish peroxidase isoenzyme C2 and its derivatives are also given. Comparison of the frequencies of the bands around 1400, 1500, 1560-1580, and 1610-1640 cm-1 with those of other hemoproteins and heme model compounds showed that in ferric highspin compounds in particular the bands are not only spin and oxidation sensitive, as has previously been reported, but that they also reflect the coordination of the heme iron. It is suggested that ferric cytochrome c peroxidase and horseradish peroxidase are pentacoordinated. In the hexacoordinated fluoride, cyanide and carbon monoxide derivatives the bands reflect the spin state and the out-of-plane position of the heme iron. The spectrum of cytochrome c peroxidase compound I supports previous studies that suggest that it has a lowspin heme iron in the Fe(IV) oxidation state.


Development of synaptic junctions in cerebellar glomeruli.
In the glomerular synapses of developing mouse cerebellar cortex, 2 components of the synaptic junctions assemble independently in the immature granule cell dendrites, and then combine. 'Initial' junctions between mossy fiber axons and immature granule cell dendrites have presynaptic and postsynaptic electron-dense fuzz and a widened synaptic cleft, but lack the aggregate of intramembrane particles associated with the extracellular half of the postsynaptic membrane which characterizes mature synaptic junctions. In the vicinity of 'initial junctions' there are particle aggregates which resemble those at mature synaptic junctions, but which are less densely packed and which are not associated with the other features of a junction. The constituent particles of these aggregates move to the sites of 'initial junctions' to combine with them and form 'immature synaptic junctions'. Many of these immature junctions are larger in area than mature synaptic junctions. The immature junctions accumulate a fairly uniform complement of intramembrane particles, which increase in packing density as the junctions decrease in area and attain smaller, adult size.


Volubility, consonant, and syllable characteristics in infants and toddlers later diagnosed with childhood apraxia of speech: A pilot study.
This pilot study explored the volubility, consonant singleton acquisition, and syllable structure development between infants and toddlers (birth-24 months) with typical speech sound production (TYP) and those later diagnosed with childhood apraxia of speech (CAS). A retrospective longitudinal between- and within-subjects research design was utilized (TYP N=2; CAS N=4). Vocalizations from participants were analyzed between birth-24 months from home videotapes, volunteered by the children's parents, according to type (nonresonant vs. resonant), volubility, place and manner of consonant singletons, and syllable shape (V, CV, VC, CVC, VCV, CVCV, VCVC, and "Other"). Volubility between groups was not significant but statistically significant differences were found in the number of: resonant and non-resonant productions; different consonant singletons; different place features; different manner classes; and proportional use of fricative, glottal, and voiceless phones. Infants and toddlers in the CAS group also demonstrated difficulty with CVCs, had limited syllable shapes, and possible regression of vowel syllable structure. Data corroborate parent reports that infants and toddlers later diagnosed with CAS present differently than do those with typical speech sound skills. Additional study with infants and toddlers later diagnosed with non-CAS speech sound disorder is needed. Readers will: (1) describe current perspectives on volubility of infants and toddlers later diagnosed with CAS; (2) describe current perspectives of the consonant singleton and syllable shape inventories of infants and toddlers later diagnosed with CAS; and (3) discuss the potential differences between the speech sound development of infants and toddlers later diagnosed with CAS and those with typical speech sound skill.


Asymmetric synthesis of druglike six-membered spirooxindoles through an amino enyne catalysis.
An effective reflexive-Michael (r-M) reaction has been disclosed to access drug-like six-membered spirooxindoles in good yields and excellent enantioselectivities by using an aminoenyne-catalysis.


Intersectionality and its relevance for research in dementia care of people with a migration background.
Despite the care and support needs of migrants affected by dementia differing from the population of the country where they live now, most European countries do not provide specific strategies to address migration in their national dementia plans. The concept of intersectionality provides an innovative approach to dementia care perspectives and methodologies. The aim is to define intersectionality and to provide examples of applying the concept to dementia care research, focusing on people with a migration background. This article was conceptualized and discussed during virtual INTERDEM taskforce meetings in 2020/2021, while discussing identified literature on intersectionality, migration, and dementia care research. Using an intersectionality framework allows understanding of a person's lived experience by considering the dimensionality, co-occurrence and interlocking of factors (e.g., sex/gender, socioeconomic status, ethnicity, migration status, geographic location/place). Intersectionality can be applied as a conceptual and methodological approach to identify and address gaps in perspectives and in (dementia care) research to overcome the threat of ignorance, exclusion and discrimination.


Semiquantitative assessment of optic nerve injury using manganese-enhanced MRI.
To evaluate the capability of manganese (Mn(2+))-enhanced MRI (MEMRI) in a continuously semiquantitative assessment of rat optic nerve (ON) injury. Forty rats were divided into three groups: (I) a control group that was submitted to MEMRI or to fluorescent labeling of retinal ganglion cells (RGCs) (n = 10); (II) an ON injury group that was submitted to MEMRI (n = 15); (III) an ON injury group that was submitted to fluorescent labeling of RGCs (n = 15). Groups II and III were examined at 3, 7, and 14 days post-lesion (dpl), when the contrast-to-noise ratio (CNR) of the retina and ON was measured on MEMRI images and the RGCs were counted by fluorescence microscopy and compared between the groups. In the control group, the intact visual pathway from the retina to the contralateral superior colliculus was visualized by MEMRI. In group II, continuous Mn(2+) enhancement was seen from the retina to the lesion site of the optic nerves at 3, 7, and 14 dpl. However, no Mn(2+) enhancement was observed distal to the lesion site at those time points. The observed Mn(2+) enhancement proximal to the ON lesion site declined between 7 and 14 dpl. The decrease in Mn(2+)-enhanced signal intensity at these sites at 7 and 14 dpl when compared to that at 3 dpl was significant (P < 0.05). The RGC density dropped by 6.84, 45.31, and 72.36 % at 3, 7, and 14 dpl, respectively. MEMRI can be used to evaluate the structural changes after optic nerve injury.


Family planning method discontinuation among Nigerian women: Evidence from the Nigeria Demographic and Health Survey 2018.
The cessation of family planning among sexually active women who do not intend to have children increases the number of unplanned pregnancies and the risks to maternal health. This study examined the predictors of family planning method discontinuation among sexually active Nigerian women. Data from the Nigeria Demographic and Health Survey (NDHS) were used. A total of 4553 women 15-49 years of age who had stopped using family planning methods in the previous 5 years were included in the study. Descriptive and binary logistic regression were used in the analysis. More than 60% of the women sampled had stopped family planning and had no intention of having children. Respondents discontinued family planning because of adverse effects (15.2%) and method failure (12.9%). Predictors of modern family planning discontinuation were secondary education (OR = 1.302, 95% CI: 1.006-1.685), Islamic religion (OR = 1.281, 95% CI: 1.059-1.550), residence in the South-East geopolitical zone (OR = 0.248, 95% CI: 0.195-0.316), having three or more children (OR = 0.848, 95% CI: 0.735-0.978) and having paid employment (OR = 0.838, 95% CI: 0.715-0.982). Socio-economic and cultural factors influence discontinuation of family planning among Nigerian women. Policy options are needed to increase family planning uptake, identify common adverse effects of family planning and focus on raising public awareness regarding the negative consequences of discontinuing family planning on individuals, families and the nation.


Selection of wound closure materials.
Selection of wound closure materials (sutures, needles, staples, and skin tapes) is presented. The characteristics of commonly used suture materials and needles are discussed as a background for their rational selection and usage. The attributes of staples and sutureless skin closures (skin tapes) are also given and contrasted with those of sutures.


Multiple patterns of 11 beta-hydroxysteroid dehydrogenase catalytic activity along the mammalian nephron.
The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is thought to be a protective enzyme of the mineralocorticoid receptor (MR). We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron. In the present study, we examined whether 11 beta-OHSD is similarly located along the nephron of other mammals. Various tubular segments were microdissected from the mouse, rat, and rabbit nephron, and incubated for two hours at 37 degrees C in the presence of 11 nM [3H]-corticosterone (B). Thereafter, the respective amounts of B and [3H]-11dehydrocorticosterone (A) in the incubation solution were measured by HPLC. In the rabbit, the mouse and the rat, about 520 pmol/10 mm of B were transformed into A in tubular segments possessing MR, that is, the distal parts of the nephron (distal and collecting tubule). Differences appeared in the aldosterone-insensitive proximal tubule; in both the initial and final parts of this segment, 11 beta-OHSD activity was low (26 pmol/10 mm) in the rabbit and the mouse, and relatively high in the rat (328 pmol/10 mm). In the cortical part of the loop of Henle, where the presence of MR is still under discussion, 11 beta-OHSD activity was low in the mouse (70 pmol/10 mm), high in the rat (533 pmol/10 mm) and intermediate in the rabbit (227 pmol/10 mm). The comparison of these results with previous data obtained with immunohistochemical methods suggests that the proximal and distal nephron might express different isoforms of 11 beta-OHSD.


Role of plasma histamine in liver injury--clinical and experimental investigations.
Plasma histamine level (PHL) was evaluated by a modified fluorometric assay (Suzuki) in the patients with various forms of liver disease as well as rabbits with liver injury. And the data obtained were compared with liver function tests in assessing the stage and prognosis of hepatic dysfunction. In acute hepatitis, if its prognosis was "good", as was also shown in the animal group with single dose administration of CCl4, the level of plasma histamine attained a peak before that of serum transaminases, and returned to normal prior to that of the latter. In persistent and chronic hepatitis, although correlation between PHL and other liver function tests was poor and variable, PHL remained high. And the estimation of PHL during the course of this state showed that it was elevated prior to that of serum transaminases, in dicating high level of plasma histamine in this state, even in apparent "steady state", worsening of the disease. In liver cirrhosis PHL correlated with the degree of serum transaminases as well as serum gammaglobulin. In "poor prognosis" group (patients with hepatic coma and rabbits treated with consecutive administration of CCl4) PHL increased extremely high, which was contrasted with the lowered levels of transaminases. These results strikingly suggest that histamine is involved in liver injury and estimation of PHL in the course of hepatic disorder is useful for a prediction of prognosis.


Functional hepatocyte-like cells derived from mouse embryonic stem cells: a novel in vitro hepatotoxicity model for drug screening.
The aim of the present study was to differentiate mouse embryonic stem (mES) cells into a high percentage of hepatocyte-like cells, and to demonstrate their utility as an in vitro hepatotoxicity model. We were able to differentiate 80-90% of mES cells using optimized hepatocyte differentiation medium. These differentiated cells showed typical hepatocyte morphology, expressed hepatic specific genes as shown by RT-PCR and displayed antibody detectable expression of markers specific for hepatic maturation. These hepatocyte-like cells also demonstrated evidence of glycogen storage. These cells when exposed to CCl4, a commonly used hepatotoxicant, showed an elevation of liver function enzymes, SGOT, SGPT and LDH, indicating hepatic damage. Further, this increase was prevented by pre-treatment with N-acetylcysteine, a known anti-oxidant. Thus we propose that the hepatocyte-like cells derived by the present method may prove to be useful as an in vitro model of hepatotoxicity, thereby providing a novel and promising alternative for obtaining large numbers of functional hepatocyte-like cells for in vitro drug metabolism and hepatotoxicity screening of potential drug candidates.


Relationship between chemically induced Ha-ras mutation and transformation of BALB/c 3T3 cells: evidence for chemical-specific activation and cell type-specific recruitment of oncogene in transformation.
BALB/c 3T3 cells were exposed to 7,12-dimethylbenz[a]anthracene (DMBA) and resultant transformed foci were analyzed for the presence of A182----T mutation at codon 61 of Ha-ras (a mutation found in many DMBA-induced animal tumors). None of the 30 independently cloned transformed cell lines contained such a mutation. In order to see whether DMBA is able to induce this mutation in BALB/c 3T3 cells, we developed a method sensitive enough to detect this specific mutation at the frequency of 10(-6). Employing this assay, we found time- and dose-dependent induction by DMBA of Ha-ras A182----T mutation in BALB/c 3T3 cells; for example, 2 wk after exposure to 100 micrograms/mL DMBA, 1.4 in 1 X 10(4) cells contained this specific mutation. On the other hand, other agents that also induce BALB/c 3T3 cell transformation, such as 3-methylcholanthrene (MCA), 12-O-tetradecanoylphorbol-13-acetate (TPA), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), or ultraviolet light, did not induce the mutation at detectable frequency (less than 10(-6)). These results suggest that DMBA efficiently induces Ha-ras mutation in BALB/c 3T3 cells but that this mutation is not recruited in the process of cell transformation. A hypothesis of carcinogen-specific mutation of Ha-ras gene and its tissue (cell type)-specific recruitment in carcinogenesis is proposed.


[Ultrasound diagnosis of vascular complications following transfemoral puncture].
Percutaneous catheter interventions are performed increasingly often for the purposes of both diagnosis and therapy. The incidence of local complications reported after transfemoral catheterization in the literature is 0.1-9%. Such complications should be detected as early and reliably as possible, and sonography is a good means of finding them during follow-up, not least because it is suitable for use in examinations at the bedside. The clinical value of sonography compared with other examination techniques is made clear with reference to specimen cases.


Characterization of a cytosolic protein (P36) isolated from pig brain by benzodiazepine-affinity chromatography.
Benzodiazepine-affinity chromatography, on a column of 1012S-Sepharose, resulted in the detection and purification of a binding protein (P36) from the cytosolic fraction of pig cerebral cortex. Purified P36 was enriched over 3,500-fold in a single step and was recovered with an efficiency of 50-60%. Analysis of the purified preparation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis demonstrated a single polypeptide of Mr 36,000. The Stokes radius (3.44 nm) and sedimentation coefficient (4.43S) indicated that purified P36 is a dimeric protein. Analysis of the amino acid composition of P36 revealed a relatively high content of the hydrophobic amino acids, valine and leucine. Immunoblotting of several pig tissue preparations with an antiserum raised against purified P36 demonstrated approximately equal enrichment of P36 in cerebral cortex, cerebellum, and adrenal glands. Lesser enrichment was observed in kidney and liver, whereas a number of other tissues displayed no immunoreactivity. The gamma-aminobutyrate/benzodiazepine receptor complex and P36 showed no immunological cross-reactivity. High-affinity binding activity for [3H]Ro 15-4513, [3H]flunitrazepam, or [3H]PK11195 was not detected in preparations of purified P36. However, the ability of the gamma-aminobutyrate/benzodiazepine receptor inverse agonists, methyl- and ethyl-beta-carboline-3-carboxylate, to inhibit the binding of P36 to 1012S-Sepharose at relatively low concentrations indicates that P36 exhibits a degree of binding specificity.


REG1A expression is an independent factor predictive of poor prognosis in patients with non-small cell lung cancer.
Regenerating gene I alpha (REG1A) is a known growth factor affecting pancreatic islet beta cells. Although REG1A expression also has been observed in various tumors, the correlation between REG1A expression and the clinicopathological characteristics of non-small cell lung cancer (NSCLC) and patient prognosis has not been evaluated. We used real-time semi-quantitative reverse transcription polymerase chain reaction to assess REG1A mRNA expression in tumor samples from 86 NSCLC patients. We then correlated REG1A mRNA expression with known clinicopathological factors. We also used immunohistochemical staining to determine the source of REG1A. Within samples of tumor tissue, the cytosol of tumor cells was stained with anti-REG1A antibody. Cells from normal tissue were not stained. The 5-year over-all survival rate among patients expressing lower levels of REG1A was significantly better than among those expressing higher levels of REG1A (P=0.0031 by log-rank test). Multivariate Cox proportional hazard analyses revealed REG1A (hazard ratio, 2.34; 95% CI, 1.25-5.90; P=0.0055) and pathological stage III (hazard ratio, 3.46; 95% CI, 1.52-14.82; P=0.0012) to be independent factors affecting the 5-year over-all survival rate. High levels of REG1A expression by tumor cells are an independent predictor of a poor prognosis in patients with NSCLC.


Effects of in utero linuron exposure on rat Wolffian duct development.
Linuron is an herbicide that displays weak androgen receptor antagonist activity. Male offspring exposed in utero to 50 mg/kg/day linuron often exhibit malformations in Wolffian duct derivatives (i.e. the epididymis and vas deferens). The objectives of this study were to determine the point during the perinatal period that linuron-induced epididymal lesions can be identified, to characterize linuron-mediated perinatal testicular and epididymal pathology, and to determine whether male rat fetuses exposed prenatally to linuron exhibit decreased intratesticular and serum testosterone (T) levels. Pregnant rats were administered corn oil vehicle or linuron by gavage at 0 or 50 mg/kg/day (n = 3 controls, 5-11 linuron-treated dams per time point) from gestation days (GD) 12 to 21 or to termination. Male fetuses or offspring were necropsied on GD 17, 19, and 21, and postnatal days (PND) 7 and 14. Epididymal malformations were not observed in fetuses from linuron-treated dams but were seen in linuron-exposed male offspring on PND 7 and 14. No testicular lesions were observed at any time point. The growth and development of linuron-exposed fetuses were altered, as evidenced by slight decreases in fetal weight and increased levels of immunoreactive proliferating cell nuclear antigen (PCNA) on GD 21. Intratesticular and serum T levels were not decreased in linuron-exposed male fetuses. These findings indicate that the adversely altered adult phenotype following in utero exposure to linuron is very similar to that produced by the antiandrogens di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP). However, the absence of testicular lesions or alterations in fetal testosterone levels would suggest that the effect of linuron on the developing Wolffian ducts is distinctly different from DBP or DEHP.


Effect of clonidine on the chronic morphine tolerance and on the sensitivity of the smooth muscles in mice.
Clonidine, when administered for prolonged period showed no tolerance to its analgesic activity. Prior exposure to clonidine attenuated the tolerance development to morphine-induced analgesia and the supersensitivity to acetylcholine (ACh) in ileum during chronic morphine treatment. Further, acute administration of lower doses of clonidine (upto 1 mg) produced supersensitivity in ileum to Ach while the higher dose (10 mg) induced subsensitivity. In vas deferens, clonidine in all the concentrations tested induced dose and time dependent supersensitivity to norepinephrine (NE) similar to that produced by morphine. Chronic clonidine treatment failed to alter the ACh responses in ileum while it produced supersensitivity to NE in vas deferens. The results suggest that clonidine and morphine possess comparable properties and the antagonism of chronic morphine tolerance by clonidine may be the therapeutic basis for its clinical application in the treatment of opiate addicts.


"Realising the potential of critical care nurses": an exploratory study of the factors that affect and comprise the nursing contribution to the recovery of critically ill patients.
This study seeks to make evident the complexity of issues associated with the delivery of care by nurses to the critically ill. Emphasis had been placed on the results and implications of these for nursing practice. For a more in-depth account, the full report can be accessed on www.lscn.co.uk. Following multi-centre research ethics committee approval, 10 critical care units participated in the 3-month study. Data collection comprised 231 nurse interviews and 51 relative interviews during 33 observation participation periods. Analysis demonstrated that the context of the critical care unit, in terms of geographical layout, unit activity, case mix and skill mix of nurses, had a major effect on the ability of nurses to contribute to the recovery of the critically ill. The effectiveness of the nursing resource appeared to be a function of knowledge (theoretical and patient related), experience and exposure. Nurses who were unused to a particular environment were not seen to be as effective as those who were. A model was constructed that identified the central tenets upon which nursing care can be optimised or compromised. When nursing care was optimised the difference nurses made potentially decreased risk to patients, enabled timely patient progression and increased the potential for patient recovery. The results confirm that nurses have a significant contribution to make in the recovery of patients who have experienced critical illness. Recommendations are far reaching and include the need to develop a valid and reliable tool which addresses patients' need for nursing in terms of nurses' knowledge and experience, patient dependency and decreasing clinical risk across the continuum of care. Current nursing workload tools and patient:nurse ratios were seen to lack validity because they do not appraise the context in which care is delivered, define all nurses as equal and concentrate on activity rather than the effect nurses can have on the outcome of the critically ill.


Traumatic intracranial haemorrhage in conscious patients with facial fractures--a review of 1959 cases.
Facial fracture patients who are conscious with a Glasgow Coma Scale (GCS) score of 15 in the absence of clinical neurological abnormalities are commonly not expected to have suffered severe intracranial pathology. However, high velocity impact may result in intracranial haemorrhage in different compartments. Over a 7-year period, 1959 facial fracture patients with GCS scores of 15 and the absence of neurological abnormalities were analysed. In 54 patients (2.8%) computed tomography scans revealed the presence of accompanying intracranial haemorrhage (study group). These patients were compared with the 1905 patients without intracranial haemorrhage (control group). Univariate analysis identified accompanying vomiting/nausea and seizures, cervical spine injuries, cranial vault and basal skull fractures to be significantly associated with intracranial bleeding. In multivariate analysis the risk was increased nearly 25-fold if an episode of vomiting/nausea had occurred. Seizures increased the risk of bleeding more than 15-fold. The mean functional outcome of the study group according to the Glasgow Outcome Scale was 4.7+/-0.7. Intracranial haemorrhage cannot be excluded in patients with facial fractures despite a GCS score of 15 and normal findings following neurological examination. Predictors, such as vomiting/nausea or seizures, skull fractures and closed head injuries, enhance the likelihood of an intracranial haemorrhage and have to be considered.


Laparoscopic enucleation of pancreatic tumours: a single-institution experience of 66 cases.
Laparoscopic enucleation of pancreatic tumours is seemingly a simple procedure, but challenging as the tumour is deeply embedded in the pancreatic parenchyma. Our study reports a single-centre experience for these cases. Cases with a tumour underwent laparoscopic enucleation from January 2014 to March 2020 in our hospital were collected and analysed. Sixty-six cases were enrolled, including 21 men and 45 women with an average age of 43.6 ± 16.7 years old. The mean size of tumours was 2.7 ± 1.8 cm. The tumours were mainly located at the pancreatic head and neck (63.6%). The most common pathological diagnoses were insulinomas, followed by solid pseudopapillary tumours. Incidences of overall complications and pancreatic fistula (PF, Grade B) were 24.2% and 19.7%, respectively. No patient developed PF (Grade C) or died. Cases were divided into two groups according to whether the tumour was deeply embedded in the pancreas. Compared to the group with a superficial tumour (n = 36), the group with an embedded tumour (n = 30) had a longer operation time and drainage duration and a smaller tumour size (P < 0.05), but did not increase the incidence of complications and PF (Grade B/C). Laparoscopic enucleation of tumours that were deeply embedded in the pancreas was technically feasible and safe.