Thoracic outlet syndrome: evaluation of the subclavian vessels by color duplex sonography.
Changes in flow in the subclavian artery and vein resulting from the use of a hyperabduction maneuver during Doppler sonography in 20 volunteers were compared with retrospective findings in 16 patients clinically suspected of having thoracic outlet syndrome. Significant compression of the subclavian artery showed in the Doppler waveform as at least a doubling of peak systolic velocity or complete cessation of flow with hyperabduction; significant compression of the subclavian vein was diagnosed by complete cessation of blood flow or loss of atrial and respiratory dynamics in the waveform of the subclavian vein with hyperabduction. In volunteers, asymptomatic compression of the subclavian vein with arm abduction was seen in two (10%) and asymptomatic compression of the subclavian artery was seen in four (20%). Of the 16 patients, thrombosis of the subclavian vein was found in seven, compression of the subclavian vein with hyperabduction was found in six, and diagnoses other than thoracic outlet syndrome were established as the cause of pain in three. When duplex sonography was compared with venography, which was performed in 10 patients, one false-negative case was found because a subclavian vein thrombus had not been detected. The subclavian artery was examined in five of the six patients with positional compression of the subclavian vein; compression of the subclavian artery was found in three. The clinical significance of compression of the subclavian artery cannot be determined from our data because of the small number of patients involved. When the sonographic criteria of subclavian vein clot or compression resulting in a complete loss of normal venous phasicity with arm abduction and the clinical criterion of subsequent improvement in symptoms after curative surgery are used, color Doppler sonography is 92% sensitive and 95% specific for the diagnosis of thoracic outlet syndrome. This preliminary study shows that Doppler sonography has potential in the evaluation of thoracic outlet syndrome.


Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemia.
p38 MAPK is activated potently during cardiac ischaemia, although the precise mechanism by which it is activated is unclear. We used the isolated perfused rat heart to investigate the signalling pathways activated upstream of p38 during global cardiac ischaemia. Ischaemia strongly activated p38alpha but not the JNK pathway. The MAPKKs, MKK3, MKK4 and MKK6 have previously been identified as potential upstream activators of p38; however, in the ischaemic perfused heart, we saw activation of MKK3 and MKK6 but not MKK4. MKK3 and MKK6 showed different temporal patterns of activity, indicating distinct modes of activation and physiological function. Consistent with a lack of JNK activation, we saw no activation of MKK4 or MKK7 at any time point during ischaemia. A lack of MKK4 activation indicates, at least in the ischaemic heart, that MKK4 is not a physiologically relevant activator of p38. The MAPKKK, ASK1, was strongly activated late during ischaemia, with a similar time course to that of MKK6 and in ischaemic neonatal cardiac myocytes ASK1 expression preferentially activated MKK6 rather than MKK3. These observations suggest that during ischaemia ASK1 is coupled to p38 activation primarily via MKK6. Potent activation of ASK1 during ischaemia without JNK activation shows that during cardiac ischaemia, ASK1 preferentially activates the p38 pathway. These results demonstrate a specificity of responses seldom seen in previous studies and illustrate the benefits of using direct assays in intact tissues responding to physiologically relevant stimuli to unravel the complexities of MAPK signalling.


Early acute aseptic iritis after cataract extraction.
Severe iritis which occurs within the first five days after cataract extraction may be categorized as (1) bacterial endophthalmitis, (2) toxic iritis, or (3) aseptic iritis. These entities can sometimes be distinguished because of their clinical features. If bacterial endophthalmitis is suspected, anterior chamber paracentesis should be considered and appropriate antibiotic treatment should be initiated. Acute iritis may result from the introduction of toxic agents into the eye, and may follow the use of products sterilized with ethylene oxide. Early acute aseptic iritis probably occurs more often than has previously been recognized. Response to intensive anti-inflammatory treatment is usually prompt and dramatic. The judicious use of cryoextraction and the careful manipulation of intraocular tissues may minimize the incidence and the severity of postoperative inflammation.


Differences in cytochrome p450-mediated pharmacokinetics between chinese and caucasian populations predicted by mechanistic physiologically based pharmacokinetic modelling.
International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines emphasize the need for better understanding of the influence of ethnicity on drug response to minimize duplication of clinical studies, thereby expediting drug approval. We have developed a Chinese database for the prediction of differences in the population kinetics of drugs mainly metabolized by cytochromes P450 (CYPs) relative to Caucasian populations. Such predictions should help to inform the need for duplication of in vivo pharmacokinetic studies in the two ethnic groups and the design of such studies. Demographic and physiological data for Chinese, along with information on CYP abundances and the frequencies of associated genetic polymorphisms in Chinese, were collated from literature sources and incorporated within the Simcyp Population-based Simulator(®) (v11.1). Default Simcyp parameter values for a virtual Caucasian population and for model compounds metabolized principally by specific CYPs were used as the point of reference. The drugs and the main CYPs involved in their metabolism were phenacetin (CYP1A2), desipramine (CYP2D6), tolbutamide (CYP2C9), omeprazole (CYP2C19), and alprazolam and midazolam (CYP3A). Hydroxy bupropion formation was used as a more sensitive marker of CYP2B6 activity than bupropion kinetics. Observed plasma drug concentration-time profiles and pharmacokinetic parameters after oral and, where possible, intravenous dosing were obtained from published in vivo studies in both Chinese and Caucasian subjects. Virtual subjects generated within Simcyp were matched to the subjects used in the in vivo studies with respect to age, sex, dosage and, where possible, CYP phenotype frequency. Predicted and observed plasma drug concentrations and weight-normalized clearances were compared between the ethnic groups. Significant differences were identified between Chinese and Caucasian populations in the frequency of CYP2C19 poor metabolizers (PMs) [Chinese 13 %; Caucasian 2.4 %], CYP2D6 PMs and intermediate metabolizers (IMs) [Chinese PMs 0.3 %, IMs 39 %; Caucasian PMs 8 %, IMs <1 %], the hepatic abundance of CYP2C19 (mean values: Chinese 8 pmol/mg; Caucasian 14 pmol/mg) and liver weight (mean values: Chinese 1198 g; Caucasian 1603 g). The observed plasma drug concentration-time profiles and weight-normalized clearances were predicted with reasonable accuracy (100 % within twofold; 89 % within 1.5-fold) in both ethnic groups. The predicted phenacetin, tolbutamide, omeprazole, desipramine, midazolam (intravenous), midazolam (oral), alprazolam (intravenous) and alprazolam (oral) clearances were 36, 25, 51, 43, 24, 17, 21 and 22 % lower, respectively, in Chinese than in Caucasians; the observed clearances were 28, 2, 75, 42, 19, 62, 20 and 21 % lower, respectively. Predicted and observed formation of hydroxy bupropion was lower in Caucasians than in Chinese (6 and 20 %, respectively). Differences between ethnic groups were less after normalization for body weight. The results of this study indicate the value of simulation based on mechanistic physiologically based pharmacokinetic modelling (PBPK) in anticipating the likely extent of any differences in the kinetics of CYP substrates in Chinese and Caucasian populations arising from demographic, physiological and genetic differences.


Slow magnetic relaxation in a lanthanide helix chain compound [Dy(HNA)(NA)₂(NO₃)]n (HNA = nicotinic acid).
A helix chain Dy(3+) compound, [Dy(HNA)(NA)2(NO3)]n (1, HNA = nicotinic acid), was synthesized under solvothermal conditions and fully characterized. The absolute configurations of the enantiomers in P6₁ and P6₅ space groups are characterized by single crystal X-ray diffraction and circular dichroism (CD). Magnetic studies reveal that compound 1 exhibits ferromagnetic interaction and slow magnetic relaxation at low temperatures with the energy barrier of 37 K under 900 Oe dc field.


[The intracardial ECG during permanent pacemaker-implantation (author's transl)].
As our researches and prevailing procedures have proved a permanent pervenous pacer implantation necessitates an additional intra-cardial ECG in parallel with the practised approach under fluoroscopy and by measuring the threshold current. The patho-physiological prerequisites are explained in detail. By means of the characteristic shape of the ST-elevation and the determination of the amplitude in mV, deciding factors for an advantageous position of the electrode may be gained. In order to ensure safe function of the demand mechanism monitoring by an intra-cardial ECG to establish a sufficient signal amplitude in mV is indispensable. This is particularly applicable in case of leads with a small surface area resulting in a low threshold current value and a low amplitude of QRS-signals.


Policy development.
The implementation of certain therapies within clinical practice is dependent on nurses taking the initiative and expanding their scope of practice. In incorporating therapies within nursing practice it is hoped that a more holistic approach to care can be achieved.


Screening and Referral for Postpartum Depression among Low-Income Women: A Qualitative Perspective from Community Health Workers.
Postpartum depression is a serious and common psychiatric illness. Mothers living in poverty are more likely to be depressed and have greater barriers to accessing treatment than the general population. Mental health utilization is particularly limited for women with postpartum depression and low-income, minority women. As part of an academic-community partnership, focus groups were utilized to examine staff practices, barriers, and facilitators in mental health referrals for women with depression within a community nonprofit agency serving low-income pregnant and postpartum women. The focus groups were analyzed through content analyses and NVIVO-8. Three focus groups with 16 community health workers were conducted. Six themes were identified: (1) screening and referral, (2) facilitators to referral, (3) barriers to referral, (4) culture and language, (5) life events, and (6) support. The study identified several barriers and facilitators for referring postpartum women with depression to mental health services.


Assessing the outcomes in patients with nonconvulsive status epilepticus: nonconvulsive status epilepticus is underdiagnosed, potentially overtreated, and confounded by comorbidity.
Nonconvulsive status epilepticus (NCSE) is characterized by behavioral or cognitive change from baseline for at least 30 minutes with EEG evidence of seizures. Categorized into complex partial status epilepticus (with lateralized seizures), and generalized nonconvulsive status epilepticus (bilateral diffuse synchronous seizures), there is debate regarding the diagnosis and morbidity of NCSE. Because EEG is needed for diagnosis, only a high index of suspicion leads to a request for the study, whereas EEG is often unavailable after hours or on weekends. Furthermore, the cognitive changes during NCSE are often incorrectly ascribed to a postictal state, intoxication, psychogenic or psychotic states, and mental retardation. Regarding categorization, present classifications address EEG features but fail to distinguish among depths of coma. Deeply comatose patients (with coma etiologies that themselves carry poor prognoses) are mixed with lightly obtunded patients with no morbidity, confusing the prognosis. Thus, a classification that subsumes depth of coma, and possibly etiology, is sorely warranted. Regarding treatment, comatose NCSE patients treated with benzodiazepines may worsen, whereas generalized nonconvulsive status epilepticus patients may suffer iatrogenically from aggressive treatment (hypotension and respiratory depression) necessitating balancing the potential neurologic morbidity of NCSE against the possible morbidity of IV antiepileptic drugs. A high index of suspicion is needed to initiate EEG studies. Better stratification of level of consciousness will be needed to distinguish among morbidity due to underlying conditions, treatment, and the effects of status epilepticus, proper.


Ouabain effect on myocardial mechanical function and sodium pump in the fetus.
Effects of ouabain (0.75, 1, 1.5, 2.5 or 5 X 10(-6) M) on the mechanical function and sodium pump were studied in the isolated arterially perfused fetal and newborn rabbit heart. Measurement of myocardial 86Rb+ active uptake was used as a marker of the sodium pump activity. The inotropic effect of ouabain in the fetus was not significantly different from that in the newborn; 2.5 X 10(-6) M ouabain caused mechanical toxicity (decrease in +dT/dtmax and increase in resting tension) in the fetus but not in the newborn. After ouabain infusion, both the inhibition of Rb+ uptake and the significant decrease in tissue potassium content were similar in the fetus and the newborn. In the fetal muscle perfused with low calcium (0.5 mM) solution, mechanical toxicity of ouabain was significantly less than in the control (1.5 mM Ca2+) solutions. High extracellular calcium (30 mM) per se caused mechanical toxicity in the fetus but not in the newborn. These data indicate that, in the isolated arterially perfused heart preparation, mechanical toxicity in the fetus is observed at lower ouabain concentrations than in the newborn. This difference in mechanical toxicity may not be explained by the age-related difference in sodium pump activity. The greater calcium toxicity in the fetus may be the reason for the increased ouabain toxicity in this age group.


Microinjection of ras p21 induces a rapid rise in intracellular pH.
Quiescent mouse NIH 3T3 cells responded to microinjection of activated ras p21 with a rapid and sustained rise in intracellular pH (approximately 0.17 pH units). The p21-induced pH change was inhibited by amiloride treatment or growth of cells in medium low in sodium, suggesting a role for the Na+/H+ antiporter. Amiloride was found to suppress p21-induced mitosis, also.


Comparison of true-colour wide-field confocal scanner imaging with standard fundus photography for diabetic retinopathy screening.
Screening of diabetic retinopathy (DR) reduces blindness by early identification of retinopathy. This study compares DR grades derived from a two-field imaging protocol from two imaging platforms, one providing a single 60-degree horizontal field of view (FOV) and the other, a standard 45-degree FOV. Cross-sectional study which included 1257 diabetic patients aged ≥18 years attending their DR screening visit in the English National Diabetic Eye Screening Programme (NDESP). Patients with maculopathy (M1), preproliferative (R2) or proliferative DR (R3) were referred to an ophthalmologist. Patients with ungradable images (U) are examined in a slit-lamp biomicroscopy clinic. Image acquisition under mydriasis of two images per eye was carried out with the EIDON and with standard fundus cameras. Evaluation was performed by masked graders. Agreement after consensus with kappa statistic was 0.89 (quadratic weights (95% CI 0.87 to 0.92)) for NDESP severity grade, 0.88 (quadratic weights (95% CI 0.82 to 0.94)) for referable disease and 0.92 (linear weights (95% CI 0.88 to 0.95)) for maculopathy. The EIDON detected clinically relevant DR features outside the 45-degree fields in two patients (0.16%): one with intraretinal microvascular abnormalities (IRMAs) and one with neovascularisation. In eight patients (0.64%), the EIDON allowed DR feature visualisation inside the 45-degree fields that were not identified in the NDESP images: three patients (0.24%) with IRMA and five patients (0.40%) with maculopathy. The rates of ungradable encounters were 12 (0.95%) and 13 (1.03%) with the EIDON and NDESP images, respectively. The EIDON identifies a small number of additional patients with referable disease which are not detected with standard imaging. This is due to the EIDON finding disease outside the standard FOV and greater clarity finding disease within the standard FOV.


Study of wild-type α-synuclein binding and orientation on gold nanoparticles.
The disruption of α-synuclein (α-syn) homeostasis in neurons is a potential cause of Parkinson's disease, which is manifested pathologically by the appearance of α-syn aggregates, or Lewy bodies. Treatments for neurological diseases are extremely limited. To study the potential use of gold nanoparticles (Au NPs) to limit α-syn misfolding, the binding and orientation of α-syn on Au NPs were investigated. α-Syn was determined to interact with 20 and 90 nm Au NPs via multilayered adsorption: a strong electrostatic interaction between α-syn and Au NPs in the hard corona and a weaker noncovalent protein-protein interaction in the soft corona. Spectroscopic and light-scattering titrations led to the determinations of binding constants for the Au NP α-syn coronas: for the hard corona on 20 nm Au NPs, the equilibrium association constant was 2.9 ± 1.1 × 10(9) M(-1) (for 360 ± 70 α-syn/NP), and on 90 nm Au NPs, the hard corona association constant was 9.5 ± 0.8 × 10(10) M(-1) (for 5300 ± 700 α-syn/NP). The binding of the soft corona was thermodynamically unfavorable and kinetically driven and was in constant exchange with "free" α-syn in solution. A protease digestion method was used to deduce the α-syn orientation and structure on Au NPs, revealing that α-syn absorbs onto negatively charged Au NPs via its N-terminus while apparently retaining its natively unstructured conformation. These results suggest that Au NPs could be used to sequester and regulate α-syn homeostasis.


Fowl cholera immunity in broiler breeder chickens determined by the enzyme-linked immunosorbent assay.
An enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies in broiler breeders vaccinated (wing web) with the CU fowl cholera vaccine. Birds were bled weekly from 9 to 26 weeks, every other week from 26 to 40 weeks, and every 4 weeks from 40 to 56 weeks of age. Overall mean ELISA antibody titers (9 to 56 weeks) reported as log10 values and survivability of the vaccinates after virulent challenge were as follows: unvaccinated--5.75, 48%; birds vaccinated once at 8 weeks--5.91, 78%; birds vaccinated twice at 8 and 14 weeks--6.11, 100%; birds vaccinated thrice at 8, 14, and 20 weeks--6.23, 100%; birds vaccinated twice at 8 and 20 weeks--6.12, 100%; and birds vaccinated twice at 8 and 20 weeks (plus fowl pox at 8 weeks)--6.08, 95%. Survivability in the vaccinates after virulent challenge with strain X-73 Pasteurella multocida was 100% in birds with ELISA antibody titers (log10) greater than 6.02. Under the conditions of this experiment, birds vaccinated two or three times between 8 and 20 weeks proved to be sufficiently immune at 56 weeks of age to withstand a virulent fowl cholera challenge. Birds not vaccinated or vaccinated only once at 8 weeks were not sufficiently immunized to withstand virulent challenge.


The cochlear nuclei--pathology.
This article is a sequel to one dealing with the anatomy of the cochlear nuclei. It employs the combined peripheral/central approach in reviewing some basic principles of the pathology of central deafness, involving the cochlear nuclei. The combined approach shows the relative status of the cochlear elements and of the superior ventral cochlear nucleus in various conditions. Anoxic encephalopathy, including that of erythroblastosis, involves the stated nucleus but spares the peripheral hearing organ. This, as well as the findings in other conditions, reflects on the employment of amplification or the implantation of electrodes. The spheroid cells, the nerve cells of concern of the superior ventral cochlear nucleus (SVCN), show an anatomic frequency gradient, low ventral to high dorsal. In any case of deafness expected to involve the SVCN and showing an audiogram frequency pattern, the frequency gradient must be included in the pathologic investigation. When the organ of Corti is completely destroyed, the spheroid cells may show transsynaptic atrophy.


Complex interactions between the sinoatrial node and atrium during reentrant arrhythmias in the canine heart.
Numerous studies implicate the sinoatrial node (SAN) as a participant in atrial arrhythmias, including atrial flutter (AFL) and atrial fibrillation (AF). However, the direct role of the SAN has never been described. The SAN was optically mapped in coronary perfused preparations from normal canine hearts (n=17). Optical action potentials were recorded during spontaneous rhythm, overdrive atrial pacing, and AF/AFL induced by acetylcholine (ACh; 0.3 to 3 micromol/L) and/or isoproterenol (Iso; 0.2 to 1 micromol/L). An optical action potential multiple component algorithm and dominant frequency analysis were used to reconstruct SAN activation and to identify specialized sinoatrial conduction pathways. Both ACh and Iso facilitated pacing-induced AF/AFL by shortening atrial repolarization. The entire SAN structure created a substrate for macroreentry with 9.6+/-1.7 Hz (69 episodes in all preparations). Atrial excitation waves could enter the SAN through the sinoatrial conduction pathways and overdrive suppress the node. The sinoatrial conduction pathways acted as a filter for atrial waves by slowing conduction and creating entrance block. ACh/Iso modulated filtering properties of the sinoatrial conduction pathways by increasing/decreasing the degree of the entrance block, respectively. Thus, the SAN could beat independently from AF/AFL reentrant activity during ACh (49+/-39%) and ACh/Iso (62+/-25%) (P=0.38). Without ACh, the AF/AFL waves captured the SAN and overdrive suppressed it. Spontaneous SAN activity could terminate or convert AFL to AF during cholinergic withdrawal. The specialized structure of the SAN can be a substrate for AF/AFL. Cholinergic stimulation not only can slow sinus rhythm and facilitate AF/AFL but also protects the intrinsic SAN function from the fast AF/AFL rhythm.


Clinical outcomes of traumatized youth in adolescent substance abuse treatment: a longitudinal multisite study.
The purpose of this study was to evaluate the effectiveness of outpatient substance abuse treatment for youth with high traumatic stress compared to youth without high traumatic stress in substance abuse treatment centers across the United States. The data for this study were gathered using a longitudinal survey design with purposive sampling from nine drug treatment delivery systems across the United States participating in the cooperative grant Strengthening Communities for Youth (SCY) awarded by SAMHSA's Center for Substance Abuse Treatment (CSAT) between September 2002 and June 2006. Follow-up assessments were conducted with the youth at three,six, and 12 months following intake. Traumatized youth responded to outpatient treatment in a similar pattern when compared to nontraumatized youth, although the traumatized youth had consistently higher scores on substance use frequency and substance problems scales than nontraumatized youth throughout the study. Current empirically validated treatments for adolescent substance abuse do not prepare the practitioner for trauma-informed practice or specifically address trauma-informed recovery. Based on our results, we advocate for the development and integration of trauma-informed practice within substance abuse treatment for adolescents to help them recover from trauma and substance abuse issues.


Structural analysis of B-Box 2 from MuRF1: identification of a novel self-association pattern in a RING-like fold.
The B-box motif is the defining feature of the TRIM family of proteins, characterized by a RING finger-B-box-coiled coil tripartite fold. We have elucidated the crystal structure of B-box 2 (B2) from MuRF1, a TRIM protein that supports a wide variety of protein interactions in the sarcomere and regulates the trophic state of striated muscle tissue. MuRF1 B2 coordinates two zinc ions through a cross-brace alpha/beta-topology typical of members of the RING finger superfamily. However, it self-associates into dimers with high affinity. The dimerization pattern is mediated by the helical component of this fold and is unique among RING-like folds. This B2 reveals a long shallow groove that encircles the C-terminal metal binding site ZnII and appears as the defining protein-protein interaction feature of this domain. A cluster of conserved hydrophobic residues in this groove and, in particular, a highly conserved aromatic residue (Y133 in MuRF1 B2) is likely to be central to this role. We expect these findings to aid the future exploration of the cellular function and therapeutic potential of MuRF1.


Dynamic Expression of Sox2, Gata3, and Prox1 during Primary Auditory Neuron Development in the Mammalian Cochlea.
Primary auditory neurons (PANs) connect cochlear sensory hair cells in the mammalian inner ear to cochlear nucleus neurons in the brainstem. PANs develop from neuroblasts delaminated from the proneurosensory domain of the otocyst and keep maturing until the onset of hearing after birth. There are two types of PANs: type I, which innervate the inner hair cells (IHCs), and type II, which innervate the outer hair cells (OHCs). Glial cells surrounding these neurons originate from neural crest cells and migrate to the spiral ganglion. Several transcription factors are known to regulate the development and differentiation of PANs. Here we systematically examined the spatiotemporal expression of five transcription factors: Sox2, Sox10, Gata3, Mafb, and Prox1 from early delamination at embryonic day (E) 10.5 to adult. We found that Sox2 and Sox10 were initially expressed in the proneurosensory cells in the otocyst (E10.5). By E12.75 both Sox2 and Sox10 were downregulated in the developing PANs; however, Sox2 expression transiently increased in the neurons around birth. Furthermore, both Sox2 and Sox10 continued to be expressed in spiral ganglion glial cells. We also show that Gata3 and Prox1 were first expressed in all developing neurons, followed by a decrease in expression of Gata3 and Mafb in type I PANs and Prox1 in type II PANs as they matured. Moreover, we describe two subtypes of type II neurons based on Peripherin expression. These results suggest that Sox2, Gata3 and Prox1 play a role during neurogenesis as well as maturation of the PANs.


Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study.
Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis. Asparaginase-associated pancreatitis was defined by at least two criteria: abdominal pain, pancreatic enzymes at least three times the upper limit of normal (ULN), and imaging compatible with pancreatitis. Patients without sufficient data for diagnostic criteria were excluded. Primary outcomes were defined as acute and persisting complications of asparaginase-associated pancreatitis and risk of re-exposing patients who suffered an episode of asparaginase-associated pancreatitis to asparaginase. Data were collected from Feb 2, 2015, to June 30, 2016, and analysed and stored in a common database at Rigshospitalet, Copenhagen, Denmark. Of 465 patients with asparaginase-associated pancreatitis, 33 (8%) of 424 with available data needed mechanical ventilation, 109 (26%) of 422 developed pseudocysts, acute insulin therapy was needed in 81 (21%) of 393, and seven (2%) of 458 patients died. Risk of assisted mechanical ventilation, need for insulin, pseudocysts, or death was associated with older age (median age for patients with complications 10·5 years [IQR 6·4-13·8] vs without complications 6·1 years [IQR 3·6-12·2], p<0·0001), and having one or more affected vital signs (fever, hypotension, tachycardia, or tachypnoea; 96 [44%] of 217 patients with affected vital signs vs 11 [24%] of 46 patients without affected vital signs, p=0·02). 1 year after diagnosis of asparaginase-associated pancreatitis, 31 (11%) of 275 patients still needed insulin or had recurrent abdominal pain or both. Both the risk of persisting need for insulin therapy and recurrent abdominal pain were associated with having had pseudocysts (odds ratio [OR] 9·48 [95% CI 3·01-35·49], p=0·0002 for insulin therapy; OR 11·79 [4·30-37·98], p<0·0001 for recurrent abdominal pain). Within 8 years of asparaginase-associated pancreatitis, risk of abdominal symptoms dropped from 8% (26 of 312) to 0% (0 of 35) but the need for insulin therapy remained constant (9%, three of 35). 96 patients were re-exposed to asparaginase, including 59 after a severe asparaginase-associated pancreatitis (abdominal pain or pancreatic enzymes at least three times the ULN or both lasting longer than 72 h). 44 (46%) patients developed a second asparaginase-associated pancreatitis, 22 (52%) of 43 being severe. Risk of persisting need for insulin or abdominal pain after having had two versus one asparaginase-associated pancreatitis did not differ (three [7%] of 42 vs 28 [12%] of 233, p=0·51). Risk of a second asparaginase-associated pancreatitis was not associated with any baseline patient characteristics. Since the risk of a second asparaginase-associated pancreatitis was not associated with severity of the first asparaginase-associated pancreatitis and a second asparaginase-associated pancreatitis did not involve an increased risk of complications, asparaginase re-exposure should be determined mainly by the anticipated need for asparaginase for antileukaemic efficacy. A study of the genetic risk factors identifying patients in whom asparaginase exposure should be restricted is needed. The Danish Childhood Cancer Foundation and The Danish Cancer Society (R150-A10181).


A clinical investigation on massage for prevention and treatment of recurrent respiratory tract infection in children.
The TCM therapeutic principle of "eliminating the pathogenic factors by supporting the healthy energy" was adopted in massage to treat and prevent recurrent respiratory tract infection of children. Susceptible and healthy children of the same age were used as controls. As a result, the therapeutic effect of the treatment group is significantly better than that of the controls, with all of the immunologic indexes being approximately normal when the patients were reexamined 3 and 6 months after the massage. Statistically, the difference was significant (P < 0.01). Massage has been proved very helpful in improving the general constitution, enhancing the immune functions, preventing and treating the condition, and in health care as well.


Survival After Coronary Revascularization With Paclitaxel-Coated Balloons.
Drug-coated balloons (DCBs) are accepted treatment strategies for coronary in-stent restenosis and are under clinical investigation for lesions without prior stent implantation. A recently published meta-analysis suggested an increased risk of death associated with the use of paclitaxel-coated devices in the superficial femoral artery. The reasons are incompletely understood as potential underlying pathomechanisms remain elusive, and no relationship to the administered dose has been documented. The purpose of this analysis was to investigate the available data on survival after coronary intervention with paclitaxel-coated balloons from randomized controlled trials (RCTs). PubMed, Web of science, and the Cochrane library database were searched, and a meta-analysis from RCT was performed comparing DCB with non-DCB devices (such as conventional balloon angioplasty, bare-metal stents, or drug-eluting stents) for the treatment of coronary in-stent restenosis or de novo lesions. The primary outcome was all-cause death. The number of patients lost to follow-up was observed at different time points. Risk estimates are reported as risk ratios (RRs) with 95% confidence intervals (CIs). A total of 4,590 patients enrolled in 26 RCTs published between 2006 and 2019 were analyzed. At follow-up of 6 to 12 months, no significant difference in all-cause mortality was found, however, with numerically lower rates after DCB treatment (RR: 0.74; 95% CI: 0.51 to 1.08; p = 0.116). Risk of death at 2 years (n = 1,477, 8 RCTs) was similar between the 2 groups (RR: 0.84; 95% CI: 0.51 to 1.37; p = 0.478). After 3 years of follow-up (n = 1,775, 9 RCTs), all-cause mortality was significantly lower in the DCB group when compared with control treatment (RR: 0.73; 95% CI: 0.53 to 1.00; p = 0.047) with a number needed to treat of 36 to prevent 1 death. A similar reduction was seen in cardiac mortality (RR: 0.53; 95% CI: 0.33 to 0.85; p = 0.009). In this meta-analysis, the use of paclitaxel DCBs for treatment of coronary artery disease was not associated with increased mortality, as has been suggested for peripheral arteries. On the contrary, use of coronary paclitaxel-coated balloons was associated with a trend toward lower mortality when compared with control treatments.


[Unusual association of Kallmann syndrome and arachnoid cyst of the middle fossa. Report of a case].
Hypogonadotrophic hypogonadism can result from different abnormalities in the central nervous system. The clinical picture depends upon the time of onset the deficiency, the magnitude of the gonadotropins deficiency and whether there are other pituitary hormone deficiencies as well. We report on a 18-year-old boy, who was investigated because of pubertal and growth delay. He also had learning disabilities. On physical examination he exhibited mild eunuchoid aspect, 162 cm height (z score = 2.17), pubertal development on stage G II, P II, and 4 cm3 testis. Laboratory investigation revealed pre-pubertal levels of testosterone and normal results of the combined test of anterior pituitary function, except for in GnRH acute and prolonged test. Brain CT showed an arachnoid cyst on left middle fossa with expansion to suprasellar cisterna. He was diagnosed as having hypogonadotrophic hypogonadism secondary to compression by the cyst, and a cyst-peritoneal derivation was performed. After surgery there was no improvement of the pubertal state and bilateral anosmia was discovered, so Kallmann's syndrome was then diagnosed and was confirmed by MRI, even though the hormonal results are not totally matched with the referred syndrome. We did not find in the literature any description of the association between Kallmann's syndrome and arachnoid cyst and we believe that in this case the results of the hormonal measurement may be due to such association that provoked an additional hypophysis dysfunction.


Locomotion in sturgeon: function of the pectoral fins.
Pectoral fins are one of the major features of locomotor design in ray-finned fishes and exhibit a well-documented phylogenetic transition from basal to derived clades. In percomorph fishes, the pectoral fins are often used to generate propulsive force via oscillatory movements, and pectoral fin propulsion in this relatively derived clade has been analyzed extensively. However, in the plesiomorphic pectoral fin condition, exemplified by sturgeon, pectoral fins extend laterally from the body in a generally horizontal orientation, have been assumed to generate lift to balance lift forces and moments produced by the heterocercal tail, and are not oscillated to generate propulsive force. The proposal that pectoral fins in fishes such as sturgeon generate lift during horizontal locomotion has never been tested experimentally in freely swimming fishes. In this paper, we examine the function of pectoral fins in sturgeon swimming at speeds from 0.5-3.0 L s(-)(1), where L is total body length. Sturgeon were studied during steady horizontal locomotion as well as while sinking and rising in the water column. Pectoral fin function was quantified using three-dimensional kinematics to measure the orientation of the fin surface, digital particle image velocimetry (DPIV) was used to describe flow in the wake of the fin and to estimate force exerted on the water, and electromyography was used to assess pectoral fin muscle function. Sturgeon (size range 25-32 cm total length) swam horizontally using continuous undulations of the body with a positive body angle that decreased from a mean of 20 degrees at 0.5 L s(-)(1) to 0 degrees at 3.0 L s(-)(1). Both the angle of the body and the pectoral fin surface angle changed significantly when sturgeon moved vertically in the water column. Three-dimensional kinematic analysis showed that during steady horizontal swimming the pectoral fins are oriented with a negative angle of attack predicted to generate no significant lift. This result was confirmed by DPIV analysis of the pectoral fin wake, which only revealed fin vortices, and hence force generation, during maneuvering. The orientation of the pectoral fins estimated by a two-dimensional analysis alone is greatly in error and may have contributed to previous suggestions that the pectoral fins are oriented to generate lift. Combined electromyographic and kinematic data showed that the posterior half of the pectoral fin is actively moved as a flap to reorient the head and body to initiate rising and sinking movements. A new force balance for swimming sturgeon is proposed for steady swimming and vertical maneuvering. During steady locomotion, the pectoral fins generate no lift and the positive body angle to the flow is used both to generate lift and to balance moments around the center of mass. To initiate rising or sinking, the posterior portion of the pectoral fins is actively moved ventrally or dorsally, respectively, initiating a starting vortex that, in turn, induces a pitching moment reorienting the body in the flow. Adjustments to body angle initiated by the pectoral fins serve as the primary means by which moments are balanced.


Ofatumumab, a human anti-CD20 monoclonal antibody.
Since relapse of chronic lymphocytic leukemia (CLL), and refractoriness to treatment following relapse, is inevitable after initial treatment, development of novel treatment strategies is necessary. CD20 as a therapeutic target for CLL, successes and limitations of current anti-CD20 monoclonal antibody (mAb) therapy, and implications of preclinical and clinical developments of novel alternatives, including ofatumumab, that may enhance anti-CD20 mAb therapy are reviewed. The literature reviewed encompasses papers and congress abstracts from the past 13 years. While rituximab combined with chemotherapy has considerably improved outcomes for some but not all CLL patients, single-agent use is limited in relapsed/refractory CLL. Novel anti-CD20 mAbs in development, such as ofatumumab, may bypass some limitations by virtue of alternative epitope binding and modified effector functions. Ofatumumab induces significant complement-dependent cell lysis in vitro, particularly in cells with low CD20 expression. The FDA recently approved ofatumumab for treatment of CLL refractory to fludarabine and alemtuzumab. CD20-targetting chemoimmunotherapeutic options have advanced treatment of CLL. Results for single-agent ofatumumab and other new CD20 mAbs, in different lines of therapy and in combination with chemotherapy, will guide optimal use of these alternative therapies for B-cell malignancies.


Molecular cloning of circular unintegrated DNA of two types of the SEATO strain of gibbon ape leukemia virus.
Closed circular unintegrated DNA of the SEATO strain of gibbon ape leukemia virus (GaLV-S) was isolated from canine thymus fibroblasts after cocultivation with chronically infected bat lung fibroblasts. Restriction endonuclease HindIII cleaves GaLV-S DNA once, thus allowing isolation and cloning of HindIII-digested unintegrated DNA in a permitted form. Two clones isolated in the vector, Charon 21A, were nearly identical by restriction enzyme mapping to each of the two types of GaLV-S previously observed. These two types differ at a single SalI site. Unlike previous maps of GaLV-S proviral DNA, however, both clones lack SstI sites in the long-terminal-repeat units. Both the GaLV-S clones and the major species of GaLV-S proviral DNA contain an EcoRI site in the long-terminal-repeat units. The presence of this EcoRI site and the absence of an SstI site in the GaLV-S long-terminal-repeat units differentiate it from all other known GaLV strains and from the closely related nononcogenic simian sarcoma-associated virus. Heteroduplex comparisons of each of the two clones to clones of simian sarcoma-associated virus show no obvious deletion or substitution loops. This suggests that the ability of GaLV-S to induce myeloid leukemia in gibbon apes in not due to an acquired onc gene.


Monitoring the changing position of coastlines using aerial and satellite image data: an example from the eastern coast of Trabzon, Turkey.
Coastline mapping and coastline change detection are critical issues for safe navigation, coastal resource management, coastal environmental protection, and sustainable coastal development and planning. Changes in the shape of coastline may fundamentally affect the environment of the coastal zone. This may be caused by natural processes and/or human activities. Over the past 30 years, the coastal sites in Turkey have been under an intensive restraint associated with a population press due to the internal and external touristic demand. In addition, urbanization on the filled up areas, settlements, and the highways constructed to overcome the traffic problems and the other applications in the coastal region clearly confirm an intensive restraint. Aerial photos with medium spatial resolution and high resolution satellite imagery are ideal data sources for mapping coastal land use and monitoring their changes for a large area. This study introduces an efficient method to monitor coastline and coastal land use changes using time series aerial photos (1973 and 2002) and satellite imagery (2005) covering the same geographical area. Results show the effectiveness of the use of digital photogrammetry and remote sensing data on monitoring large area of coastal land use status. This study also showed that over 161 ha areas were filled up in the research area and along the coastal land 12.2 ha of coastal erosion is determined for the period of 1973 to 2005. Consequently, monitoring of coastal land use is thus necessary for coastal area planning in order to protecting the coastal areas from climate changes and other coastal processes.


RFE based chondroplasty in wrist arthroscopy indicates high risk for chrondocytes especially for the bipolar application.
The application of radiofrequency energy (RFE) has become widespread for surgical performed chondroplasty especially due to the anticipated sealing effect, however the safety of this procedure in the wrist remains unclear. The purpose of this study was to investigate the subchondral temperature during radiofrequency energy (RFE) application simulating chondroplasty in an arthroscopic setting of the wrist. A chondroplasty of the lunate fossa was performed during an arthroscopy setting on 14 cadaver arms using monopolar or bipolar RFE. The temperature was recorded simultaneously from 7 predefined anatomical landmarks. The mean temperature for both application modes did not exceed more than 30°C at all measured points, except for the lunate fossa. The highest subchondral measured peak temperature was 49.35°C (monopolar) and 69.21°C (bipolar) in the lunate fossa. In addition, the temperature decreased for both radiofrequency (RF) devices depending on the distance of the sensors to the RF-probe. It remains to be questionable how safe RFE can be used for chondroplasty in wrist arthroscopy under continuous irrigation and constant movement to obtain the desired sealing effect. However, the bipolar device should be applied with more caution since peak temperature in the lunate fossa almost reached 70°C even under continuous irrigation.


Prospective characterization of protracted bacterial bronchitis in children.
Prior studies on protracted bacterial bronchitis (PBB) in children have been retrospective or based on small cohorts. As PBB shares common features with other pediatric conditions, further characterization is needed to improve diagnostic accuracy among clinicians. In this study, we aim to further delineate the clinical and laboratory features of PBB in a larger cohort, with a specific focus on concurrent viral detection. Children with and without PBB (control subjects) undergoing flexible bronchoscopy were prospectively recruited. Basic immune function testing and lymphocyte subset analyses were performed. BAL specimens were processed for cellularity and microbiology. Viruses were identified using polymerase chain reaction (PCR) and bacteria were identified via culture. The median age of the 104 children (69% male) with PBB was 19 months (interquartile range [IQR], 12-30 mo). Compared with control subjects, children with PBB were more likely to have attended childcare (OR, 8.43; 95% CI, 2.34-30.46). High rates of wheeze were present in both groups, and tracheobronchomalacia was common. Children with PBB had significantly elevated percentages of neutrophils in the lower airways compared with control subjects, and adenovirus was more likely to be detected in BAL specimens in those with PBB (OR, 6.69; 95% CI, 1.50-29.80). Median CD56 and CD16 natural killer (NK) cell levels in blood were elevated for age in children with PBB (0.7 × 109/L; IQR, 0.5-0.9 cells/L). Children with PBB are, typically, very young boys with prolonged wet cough and parent-reported wheeze who have attended childcare. Coupled with elevated NK-cell levels, the association between adenovirus and PBB suggests a likely role of viruses in PBB pathogenesis.


A nineteen-year cohort study on the relationship of electrocardiographic findings to all cause mortality among subjects in the national survey on circulatory disorders, NIPPON DATA80.
Electrocardiogram (ECG) is one of the most popular tools for daily clinics and health checkup, and has been used for the National Survey on Circulatory Disorders to assess the health status in Japanese people. The meaningfulness to predict mortality from all causes among people with ECG abnormality is to be clarified using national samples. ECG findings recorded among 9,638 subjects for National Survey on Circulatory Disorders 1980 in Japan, were classified using the Minnesota Codes (mc). Their relationships to all cause mortality over 19 years were examined using Cox proportional hazard models adjusting for sex, age, systolic blood pressure, blood glucose, and smoking habits. Subjects with abnormal Q-QS findings showed significantly high hazard ratios ( 3.71(mc1-1) and 1.57 (mc1-3)) for mortality to the subjects who were free from any major ECG findings. Hazard ratios were 1.37 (mc2-1) to 4.16 (mc2-5) for axis deviation, and 1.34 (mc3-1) to 1.35 (mc3-3) for left high R waves. Those were 1.63 (mc4-3) to 2.59 (mc4-1) for ST depression, and 1.54 (mc5-3) to 2.33 (mc5-1) for T abnormality. The lower the second number of the Minnesota Codes was, the higher hazard ratio was observed in the Q-QS, ST, T codes. The hazard ratios of junction-type ST depression (mc4-4), and low T waves (mc5-4, 5-5) were not significant. ECG findings defined by the Minnesota Codes were useful to predict the risk for mortality from all causes even after adjusting for the other major risk factors, and the results supported a usefulness of the ECG for health check-ups.


Induced sputum and bronchoalveolar lavage as tools for evaluating the effects of inhaled corticosteroids in patients with asthma.
Changes in airway inflammation can be studied with bronchoalveolar lavage, but the widespread use of this procedure is limited by its invasiveness. The aim of this study was to evaluate the usefulness of induced sputum as a non-invasive alternative to bronchoalveolar lavage for studying changes in airway inflammation in patients with asthma. Thirty patients were treated for 12 weeks with an inhaled corticosteroid (fluticasone propionate (FP), 250 microg twice daily) or a short-acting beta-agonist (salbutamol (Sb), 400 microg twice daily) in a double-blind, double-dummy, randomized parallel group study. Sputum induction with hypertonic saline solution was performed twice before treatment and after 4, 8, 10, and 11 weeks of treatment. Bronchoalveolar lavage fluid divided into two pools (first 60 mL portion as bronchoalveolar lavage/bronchial wash (BAL/BW) and subsequent 80 mL as bronchoalveoalar lavage (BAL)) was obtained before and after 12 weeks of treatment. Changes in cell differentials and plasma-protein leakage (alpha2-macroglobulin, albumin, and their ratio (relative coefficient of excretion, RCE)) were analyzed in induced sputum and were compared with changes in BAL/BW and BAL. During treatment with FP, the PC20histamine (interpolated concentration of histamine that caused a fall in FEV1 of 20% of the baseline value) increased (P < .0001), and the percentage of eosinophils (P = .004), levels of (alpha2-macroglobulin (P = .09) and RCE (P = .007) decreased in sputum. These changes were different from those in the Sb group (PC20histamine P< .0001, eosinophils P= .004, alpha2-macroglobulin P= .003, RCE P = .01), in which alpha2-macroglobulin showed a significant increase (P = .015). Changes in the percentage of eosinophils and in the levels of alpha2-macroglobulin in sputum were associated with changes in the PC20histamine (Rs = -0.59, P = .007 and Rs = -0.47, P = .03, respectively). These correlations did not reach significance in BAL/BW and BAL fluid. The statistical power to detect changes in induced sputum was higher for the percentage of eosinophils and similar for plasma protein leakage as compared with analysis of BAL/BW and BAL fluid. We conclude that the analysis of induced sputum is a useful, non-invasive alternative to bronchoalveolar lavage for assessing the effects of antiinflammatory drugs in asthma.


What do recent human studies tell us about the association between anaesthesia in young children and neurodevelopmental outcomes?
Anaesthetic and sedative drugs transiently disrupt normal neural activity to facilitate healthcare procedures in children, but they can also cause long-term brain injury in experimental animal models. The US Food and Drug Administration (FDA) has recently advised that repeated or lengthy exposures to anaesthetic and sedative drugs prior to 3 yr of age have the potential to harm the development of children's brains and added warnings to these drug labels. Paediatric anaesthesia toxicity could represent a significant public health issue, and concern about this potential injury in children has become an important issue for families, paediatric clinicians and healthcare regulators. Since late 2015, important new data from five major clinical studies have been published. This narrative review aims to provide a brief overview of the preclinical and clinical literature, including a comprehensive review of these recent additions to the human literature. We integrate these new data with prior studies to provide further insights into how these clinical findings can be applied to children.


A Comparison of Four 3-Axis-Accelerometers for Monitoring Hospital Pneumatic Tube Systems.
Validation of hospital pneumatic tube systems (PTS) is recommended to predict and prevent errors caused by sample hemolysis. 3-Axis accelerometer dataloggers have been successfully implemented as tools for PTS validation, but the most suitable device for such validation has not been investigated. The aim of this study was to evaluate the performance of four commercially available 3-axis accelerometers for PTS validation. PCE-VD3 (PCE), CEM DT-178A (CEM), Extech VB300 (EXT), and MSR 145 (MSR) dataloggers were placed into a single PTS carrier and repeatedly transported through one of three PTS routes. The number and magnitude of accelerations within each PTS route was collected by each device. Deming regression analysis was used to compare device performance. The MSR datalogger captured the greatest number of g-forces >3 g, 5 g, 10 g, and 15 g, and the greatest magnitude of g-force (26.7 g) relative to the other devices (CEM: 23.0 g, EXT: 23.3 g, PCE: 23.7 g). As a result of increased sampling frequency, the MSR recorded the lowest AUC and the greatest number of g-forces exceeding 3 g relative to the other devices. Subjectively, the data were difficult to extract from 4 tested devices. Commercially available dataloggers differ in their ability to detect the number and magnitude of g-forces within PTSs. We recommend that one device be used to perform all PTS evaluations, with baseline evaluations for tolerable AUC, number, and magnitude of g-forces established internally. Lack of harmonization, cumbersome data processing, and time-consuming data analysis are substantial barriers to universal implementation of dataloggers for PTS validation and monitoring.


Simulated surgical workshops enhance medical school students' preparation for clinical rotation.
A major focus of the medical school curriculum is to ensure medical students are well prepared prior to entering clinical rotations, which includes the compulsory surgical rotation. The objective of this research was to design and formally evaluate a set of real-life surgical workshops aimed at better preparing medical students for their clinical rotation in surgery. These workshops would be incorporated into the pre-clinical medical school curriculum. Dedicated surgical workshops were introduced into the preclinical component of the Bachelor of Medicine/Bachelor of Surgery (MBBS) program at our University in 2009. These workshops encompassed training in the clinical skills needed in the perioperative and wider hospital setting. A survey comprising of eight to nine ranked questions (utilising a five-point Likert Scale) as well as three short answer questions was administered to the medical students after they completed their compulsory surgical clinical rotation. The overall response rate to the survey evaluating the surgical workshops was 79% (123/155). The mean of the ranked questions ranged from 4.05 to 4.89 which indicated that the students found the workshops useful. When evaluating the short answer questions (via topic coding), additional information was provided that supported and explained the survey findings and also included suggestions for improvements. The findings of the medical student survey demonstrated the value of incorporating dedicated preparatory surgical workshops in the medical school pre-clinical curriculum. However, further research is warranted to determine if this inclusion translated into improved student performance during the clinical surgical rotation.


Patients with multiple myeloma develop SOX2-specific autoantibodies after allogeneic stem cell transplantation.
The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS). However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM). Screening 1094 peripheral blood (PB) sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2(211-230) as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients' BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT). Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n = 74). Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.


[Survival prognostic factors in a cohort of patients with esophageal carcinoma].
The epidemiology of esophageal carcinoma (EC) has changed in the last decades. Adenocarcinoma and squamous cell carcinoma are analyzed as a single condition because prognosis is similar. The aim of this study was to define prognostic factors in EC, considering each histopathologic type independently. We studied a retrospective cohort of patients treated from 1981 to 2001 at the National Cancer Institute (Instituto Nacional de Cancerología, INCan) in Mexico City. Patients with EC (including siewert I type neoplasms), with endoscopic biopsy, of adenocarcinoma or squamous cell carcinoma older than 18 years of age, and with complete clinical evaluation were included in the study. A total of 236 cases were included: 60 (25.4%) were adenocarcinoma and 176 (74.6%), squamous cell carcinoma. Median survival times were 5.2 months (95% CI, 0.7 to 9.6) and 2.9 months (95% CI, 2.2 to 3.6 months), respectively (p = 0.0042). In bivariate analysis, age, histopathologic type, T classification, M classification, differentiation grade, history of hiatal hernia, presence of Barrett esophagus, anemia, surgical resection, and use of other antineoplastic treatments were related to survival (p = 0.00001). At our hospital, EC is a lethal neoplasia with a dismal prognosis. Adenocarcinoma has a better prognosis than squamous cell carcinoma. However, in multivariate analysis, T classification and possibility of surgical resection were the most important prognostic factors determining survival.


[Spontaneous closure of the interventricular septal defects in children].
A total of 214 patients with a defect of the interventricular septum have been examined starting from the first days of their life and to the age of 7 years. In 50 of them the defect closed spontaneously (23.4 per cent). Twenty of these patients had a complicated course of the defect (circulatory insufficiency, colds and pneumonia). The spontaneous closure of the interventricular septum defect occurred most frequently at the age of from 1 to 4 years (86 per cent).


Research on fatigue identification methods based on low-load wearable ECG monitoring devices.
The identification of fatigue in personal workers in particular environments can be achieved through early warning techniques. In order to prevent excessive fatigue of medical workers staying in infected areas in the early phase of the coronavirus disease pandemic, a system of low-load wearable electrocardiogram (ECG) devices was used as intelligent acquisition terminals to perform a continuous measurement ECG collection. While machine learning (ML) algorithms and heart rate variability (HRV) offer the promise of fatigue detection for many, there is a demand for ever-increasing reliability in this area, especially in real-life activities. This study proposes a random forest-based classification ML model to identify the four categories of fatigue levels in frontline medical workers using HRV. Based on the wavelet transform in ECG signal processing, stationary wavelet transform was applied to eliminate the main perturbation of ECG in the motion state. Feature selection was performed using ReliefF weighting analysis in combination with redundancy analysis to optimize modeling accuracy. The experimental results of the overall fatigue identification achieved an accuracy of 97.9% with an AUC value of 0.99. With the four-category identification model, the accuracy is 85.6%. These results proved that fatigue analysis based on low-load wearable ECG monitoring at low exertion can accurately determine the level of fatigue of caregivers and provide further ideas for researchers working on fatigue identification in special environments.


A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila.
Forward genetic screens in model organisms have provided important insights into numerous aspects of development, physiology and pathology. With the availability of complete genome sequences and the introduction of RNA-mediated gene interference (RNAi), systematic reverse genetic screens are now also possible. Until now, such genome-wide RNAi screens have mostly been restricted to cultured cells and ubiquitous gene inactivation in Caenorhabditis elegans. This powerful approach has not yet been applied in a tissue-specific manner. Here we report the generation and validation of a genome-wide library of Drosophila melanogaster RNAi transgenes, enabling the conditional inactivation of gene function in specific tissues of the intact organism. Our RNAi transgenes consist of short gene fragments cloned as inverted repeats and expressed using the binary GAL4/UAS system. We generated 22,270 transgenic lines, covering 88% of the predicted protein-coding genes in the Drosophila genome. Molecular and phenotypic assays indicate that the majority of these transgenes are functional. Our transgenic RNAi library thus opens up the prospect of systematically analysing gene functions in any tissue and at any stage of the Drosophila lifespan.


The quest for developing new treatments from imaging techniques: promises, problems and future potential.
Drug discovery and development in psychiatry is beset by many challenges, both those which are associated with the development process in general (and affecting all of medicine) and others, which are unique to psychiatry. Due to these factors, marginal progress has been achieved in the past as many features of serious mental illness remain untouched by existing treatments. Arguably, the most important of these drug targets is cognitive dysfunction, which strongly predicts clinical outcome in a number of major neuropsychiatric conditions. Therefore, a critical need exists for progress in the characterization of this and other targets for drug discovery and development. A key area, which is already showing promise, is the use of non-invasive functional neuroimaging to investigate both cognitive dysfunction and its remediation with novel agents. In this article, the authors describe the paradigmatic case of cognitive dysfunction in schizophrenia, and the prospects for using functional magnetic resonance imaging (fMRI) to investigate the effects of agents targeting cognition. The authors observe a number of advantages of this approach over other methodologies, as well as some significant issues to be resolved in the application of this technology. The authors propose that pharmaco-fMRI is emerging as a major tool to enhance the drug development process in order to bring truly novel treatments to patients with a range of neuropsychiatric disorders.


Point-of-care ultrasound findings in unselected patients in an emergency department -results from a prospective observational trial.
Point-of-care ultrasound (POCUS) can improve patient management in the emergency department (ED). However, previous studies have focused only on selected groups of patients, such as trauma, shock, dyspnea, or critically ill patients, or patients with an already known diagnosis. Most patients seen in the ED do not match these criteria. We aim to present total prevalence of positive findings when basic POCUS is applied to the broad population of patients seen in an emergency department. We conducted a single-center prospective explorative observational study of 405 unselected patients aged 18 years or over. A structured whole-body ultrasound examination was performed on all patients within 2 h of arrival to the ED. The ultrasound examination consisted of focused cardiac ultrasound, focused abdominal ultrasound, focused assessment with sonography for trauma (FAST), and focused lung ultrasound. We managed to perform 94.5% of all planned examinations. The study revealed positive findings in 39.3% of all included patients. This study presents the prevalence of positive findings among subgroups of patients. Divided among the categories of chief complaint, we found 62 positive examinations in 58 (14.3%; 95% CI, 10.9-17.7) unique patients with orthopedic complaints, 77 positive examinations among 59 (14.6%; 95% CI, 11.1-18.0) unique patients with medical complaints, and 55 positive examinations among 42 (10.4%; 95% CI, 7.4-13.3) unique patients with abdominal surgical complaints. POCUS revealed positive findings in more than one third of unselected patients in the emergency department. The study presents the findings and distribution among categories of chief complaints. Future investigations are necessary to elucidate the implication of the findings.


Frequency of signs of excited delirium syndrome in subjects undergoing police use of force: Descriptive evaluation of a prospective, consecutive cohort.
There has, to date, been no prospective description of the frequency with which police officers encounter individuals who display signs of excited delirium syndrome (ExDS). The ability to document the relationship between signs of excited delirium and subject outcomes and then determine the underlying pathophysiology that results in morbidity and mortality is necessary in order to determine the case definition for ExDS in live individuals. We prospectively evaluated the frequency of signs of ExDS in a cohort of consecutive subjects undergoing use of force by law enforcement officers (LEOs) and determined the frequency with which those features were encountered alone and in combination. Data were collected prospectively for all subjects undergoing use of force (UOF) by LEOs in a single police agency from August 2006 until August 2009. Ten previously published signs of ExDS were prospectively recorded by officers: pain tolerance, constant/near constant physical activity, not responding to police presence, superhuman strength, rapid breathing, not tiring despite heavy physical exertion, naked/inappropriately clothed, sweating profusely, hot to the touch, and attraction to/destruction of glass/reflective surfaces. UOF occurred in 1269 of 1.56 million police-public interactions (0.08%, 95% CI 0.08, 0.086). Of subjects undergoing police use of force, 1101/1269 or 86.8% (95% CI 84.8%, 88.6%) were assessed as having effects of emotional disturbance, drugs, alcohol or a combination of these comorbidities at the scene at the time of the UOF and 837/1269 or 66% (95% CI 63.3, 68.6) were violent at the time of the UOF. Excluding violence, 655/1269 (51.6% 95% CI 48.8, 54.4) had no signs of ExDS at the time of UOF and another 405/1269 (31.9% 95% CI 29.4, 34.6%)) had only one or two signs of ExDS at the time of UOF. The remaining 209/1269 (16.5%, 95% CI 14.5, 18.6) had 3 or more concomitant signs of ExDS at the time of UOF. One person died in our cohort who was experiencing 10 concomitant features of ExDS at the time of the UOF event. With only one death in our 3 year prospective cohort, we cannot comment on causality or correlation between number of Excited Delirium signs and mortality. Further study must be undertaken to determine whether correlation exists between higher numbers of ExDS signs and physiologic measures of acute underlying pathology in live subjects. Law enforcement officers and other prehospital care providers can recognize and describe symptoms of ExDS in the field at the time of interaction. Even though police use of force is rare over 15%, or approximately 1 in 6, of individuals undergoing police UoF have 3 or more concomitant signs of Excited Delirium at the time of the UoF event. The single death in our cohort occurred in an individual with 10 concomitant signs of ExDS. Future work including further clinical outcome data will determine whether higher numbers of concomitant signs of ExDS predicts subject morbidity or mortality and whether any specific symptoms or symptom cluster is associated with death. If so, a case definition will be able to be fully described.


Implementation and assessment of an electronic clinical decision support tool to notify clinicians of critical hyperbilirubinemia in preterm neonates less than 35 weeks' gestation.
Critical hyperbilirubinemia in preterm neonates, a condition requiring greater attention, is treated with phototherapy or exchange transfusion when bilirubin results exceed gestational age and age-specific medical decision levels (MDLs) to prevent bilirubin-induced neurologic damage. Conventional evaluation involves multiple manual steps and is poised to inconsistencies and delays. We designed and implemented an electronic clinical decision support (CDS) tool to identify and alert neonatal intensive care unit clinicians of critical hyperbilirubinemia with a SmartZone alert. We evaluated the performance of our manual evaluation workflow, the accuracy of the electronic CDS tool, and the outcome of the electronic CDS tool to reduce the time to place orders for interventions. Among the 22 patients who met the criteria to have phototherapy ordered before implementing the electronic CDS tool, 20 (90%) had phototherapy ordered. Fourteen (70%) phototherapy orders were placed less than 24 hours, 4 phototherapy orders were placed 24 to 72 hours, and 2 orders were placed more than 72 hours after bilirubin results exceeded the corresponding MDLs. Among the 15 patients who met the criteria to have phototherapy ordered after implementing the electronic CDS tool, all (100%) received phototherapy orders, with 14 (93%) placed less than 24 hours and 1 order placed less than 48 hours. The electronic CDS tool identified all eligible patients correctly. The proportion of phototherapy ordered less than 24 hours increased from 70% to 93% after the implementation of the electronic CDS tool. The electronic CDS tool promoted more appropriate and timely intervention orders to manage critical hyperbilirubinemia in preterm neonates.


History of lasers in dermatology.
In the 1950s, based on the theory of stimulating radiant energy published by Albert Einstein in 1916, the collaboration of physicists and electrical engineers, searching for monochromatic radiation to study the spectra of molecules, led to the invention of the first laser in 1960. Ophthalmologists and dermatologists were the first to study the biological effects and therapeutic possibilities of laser beams. The construction of new laser systems emitting energy at different wavelengths or with different durations, as well as the development of new concepts of the biomedical effects, led to its broad use in surgery in the treatment of vascular and pigmented lesions as well as cosmetic applications.


Functional and biochemical characterisation of the Toxoplasma gondii succinate dehydrogenase complex.
The mitochondrial electron transport chain (mETC) is a series of membrane embedded enzymatic complexes critical for energy conversion and mitochondrial metabolism. In commonly studied eukaryotes, including humans and animals, complex II, also known as succinate dehydrogenase (SDH), is an essential four-subunit enzyme that acts as an entry point to the mETC, by harvesting electrons from the TCA cycle. Apicomplexa are pathogenic parasites with significant impact on human and animal health. The phylum includes Toxoplasma gondii which can cause fatal infections in immunocompromised people. Most apicomplexans, including Toxoplasma, rely on their mETC for survival, yet SDH remains largely understudied. Previous studies pointed to a divergent apicomplexan SDH with nine subunits proposed for the Toxoplasma complex, compared to four in humans. While two of the nine are homologs of the well-studied SDHA and B, the other seven have no homologs in SDHs of other systems. Moreover, SDHC and D, that anchor SDH to the membrane and participate in substrate bindings, have no homologs in Apicomplexa. Here, we validated five of the seven proposed subunits as bona fide SDH components and demonstrated their importance for SDH assembly and activity. We further find that all five subunits are important for parasite growth, and that disruption of SDH impairs mitochondrial respiration and results in spontaneous initiation of differentiation into bradyzoites. Finally, we provide evidence that the five subunits are membrane bound, consistent with their potential role in membrane anchoring, and we demonstrate that a DY motif in one of them, SDH10, is essential for complex formation and function. Our study confirms the divergent composition of Toxoplasma SDH compared to human, and starts exploring the role of the lineage-specific subunits in SDH function, paving the way for future mechanistic studies.


Soil-Plant Relationships in Soybean Cultivated under Crop Rotation after 17 Years of No-Tillage and Occasional Chiseling.
No-tillage cover crops contribute to better soil quality, being able to replace mechanized tillage management. This observation can only be made after several years of adopting conservationist practices and through research on soil-plant relationships. The objective of the research was to verify the relationship between the production components, physiological, root development, and physical-hydric properties of the soil in the yield of soybean grown in succession to different cover crops or with soil chiseling. The experiment was carried out in a randomized block design with four replications, comparing the cultivation of sunn hemp (Crotalaria juncea) and millet (Penninsetum glaucum L.) as cover crops and a treatment with soil chiseling. The evaluations were carried out during soybean (Glycine max L.) cultivation in the 2019/20 summer crop, that is, after 17 years of experimenting started in 2003. Rotation with sunn hemp increased soybean yield by 6% and 10%, compared with millet rotation and soil chiseling. The species used in crop rotation in a long-term no-tillage system interfere with the physical and water characteristics of the soil, affecting the physiological responses and soybean yield. The rotation with sunn hemp offers greater water stability to the plants and provides greater soybean yield in succession. Future research that better addresses year-to-year variation, architecture, and continuity of pores provided by crop rotation, and evaluations of gas exchange, fluorescence, and activities of stress enzymes in soybean plants may contribute to a better understanding of soil-plant relationships in long-term no-till.


Monitoring impedance changes associated with motility and mitosis of a single cell.
We present a device enabling impedance measurements that probe the motility and mitosis of a single adherent cell in a controlled way. The micrometre-sized electrodes are designed for adhesion of an isolated cell and enhanced sensitivity to cell motion. The electrode surface is switched electro-chemically to favour cell adhesion, and single cells are attracted to the electrode using positive dielectrophoresis. Periods of linear variation in impedance with time correspond to the motility of a single cell adherent to the surface estimated at 0.6 μm h(-1). In the course of our study we observed the impedance changes associated with mitosis of a single cell. Electrical measurements, carried out concomitantly with optical observations, revealed three phases, prophase, metaphase and anaphase in the time variation of the impedance during cell division. Maximal impedance was observed at metaphase with a 20% increase of the impedance. We argue that at mitosis, the changes detected were due to the charge density distribution at the cell surface. Our data demonstrate subtle electrical changes associated with cell motility and for the first time with division at the single-cell level. We speculate that this could open up new avenues for characterizing healthy and pathological cells.


Tumor cell proteinase visualization and quantification using a fluorescent transition-state analog probe.
The fluorescent proteinase transition-state analog inhibitor, dansyl-L-argininal (DnsArgH), may be a selective probe of cysteine and serine-type proteinases in a fibrosarcoma tumor cell line (HSDM1C1). DnsArgH binds with high affinity to proteinases because of its transition-state analog properties, and on association it gives a dramatically increased fluorescent yield. The DnsArgH binding is inhibited by the serine proteinase inhibitor diisopropyl fluorophosphate and by the cysteine proteinase inhibitor p-chloromercuribenzoate. The fluorescence emission appears at its maximum steady-state yield immediately on addition of DnsArgH to the HSDM1C1 fibrosarcoma cells. The immediacy of the DnsArgH reaction supports the contention that DnsArgH binding may be to cell surface-associated proteinases. Quantification of the cell proteinase concentration, by comparison of the fluorescence yield obtained from DnsArgH interactions with bovine trypsin and papain, indicates 10(-15) to 10(-16) mol of proteinase per HSDM1C1 cell. In fluorescence microscopy, DnsArgH fluorescence appears distributed throughout the fibrosarcoma cell without association to organelles. DnsArgH fluorescence from normal fibroblast controls (IMR-90) was found to be substantially lower than in the transformed fibrosarcoma cells, supporting a hypothesis that proteinases have a role in malignancy.


A new system for continuous intravenous infusion of pigs.
The swivel system described has been used by ILOB-TNO for prolonged periods of continuous infusion. It allows for less restricted movement of animals. The swivel prevents the infusion tube from twisting. The swivel system is simple, safe to operate and cost-effective. Animals have greater movement, can stretch and turn around. The physical discomfort and psychological stress of restricted movement are greatly reduced. The potentially complicating/confusing effects on the measurements taken during an experiment are reduced.


Validity and reliability of the Fagerstrom Test for Cigarette Dependence in a sample of Arabic speaking UK-resident Yemeni khat chewers.
The Fagerstrom Test for Cigarette Dependence (FTCD) (formally FTND) is widely used for measuring physical dependence on nicotine. To explore the cross cultural validity and reliability of FTCD amongst Arabic speaker cigarette consumers who chew khat leaf, a stimulant green leaf. The psychometric properties of the FTCD were assessed in a subsample (91 regular cigarette smokers) of purposively selected 204 UK-resident Yemeni khat chewers recruited during random visits to khat sale outlets. Data were collected via a structured face-to-face interview. Data analyses included descriptive tests and factor analysis. Two factors were obtained by a principle axis factor analysis and these were termed as urgency of restoring the level of nicotine after abstinence during sleeping and maintaining the level of nicotine during waking. The internal reliability (Cronbach's alpha coefficient) of the whole FTCD is low (.68) as well as for the two subscales (.60) and (.62) respectively. The psychometric properties of the Arabic version of the FTCD scale in this sample of Yemeni khat chewers who smoked regularly confirmed what has been established in other cultural settings. The findings of this study have yet to be cross validated amongst other appropriately representative sample of Arabic speakers.


Pharmacoprevention of tobacco smoke effects on macrophage cells.
Cigarette smoke components produce a variety of morphologic, physiologic, biochemical, and enzymatic changes in pulmonary alveolar macrophages, cells which are important in pulmonary antibacterial defenses, cellular regulatory activity, and tissue pathogenesis of inflammation, proteolysis and fibrogenesis. A common denominator of enzymes found to be inhibited by cigarette smoke components is a sulfhydryl moiety which is critical to the functioning of the enzyme and highly susceptible to oxidant activity of substances with the properties of agents in cigarette smoke. The inhibitory effect of cigarette smoke components on glyceraldehyde 3-phosphate dehydrogenase, calcium and magnesium ATPase, and endoperoxide E-isomerase is quantitatively prevented by the addition of sulfhydryl agents such as glutathione and cysteine. Furthermore, critical functions of whole cell activity such as phagocytosis, energy metabolism, and prostaglandin synthesis and release, functions which are dependent on sulfhydryl enzymes and are inhibited by cigarette smoke components, are protected when glutathione or cysteine are provided in advance of the exposure. These sulfhydryl agents also protect adhesion and cellular morphology from derangement by cigarette smoke components. These in vitro studies suggest a role for sulfhydryl-containing agents in the prevention of environmentally-induced injuries to alveolar macrophages.


A flexible kinetic assay efficiently sorts prospective biocatalysts for PET plastic subunit hydrolysis.
Esterase enzymes catalyze diverse hydrolysis reactions with important biological, commercial, and biotechnological applications. For the improvement of these biocatalysts, there is a need for widely accessible, inexpensive, and adaptable activity screening assays that identify enzymes with particular substrate specificities. Natural systems for biopolymer bioconversion, and likely those designed to mimic them, depend on cocktails of enzymes, each of which specifically targets the intact material as well as water-soluble subunits of varying size. In this work, we have adapted a UV/visible assay using pH-sensitive sulfonphthalein dyes for the real-time quantification of ester hydrolysis of bis-(2-hydroxyethyl) terephthalate (BHET), a subunit of polyethylene terephthalate (PET) plastic. We applied this method to a diverse set of known PET hydrolases and commercial esterases in a microplate format. The approach identified four PET hydrolases and one commercial esterase with high levels of specificity for BHET hydrolysis. Five additional PET hydrolases and three commercial esterases, including a thermophilic enzyme, effectively hydrolyzed both BHET and its monoester product MHET (mono-(2-hydroxyethyl) terephthalate). Specific activities were discernible within one hour and reactions reached an unequivocal endpoint well within 24 hours. The results from the UV/visible method correlated well with conventional HPLC analysis of the reaction products. We examined the suitability of the method toward variable pH, temperature, enzyme preparation method, mono- and multi-ester substrate type, and level of sensitivity versus stringency, finding the assay to be easily adaptable to diverse screening conditions and kinetic measurements. This method offers an accurate, easily accessible, and cost-effective route towards high-throughput library screening to support the discovery, directed evolution, and protein engineering of these critical biocatalysts.


Management of biochemically recurrent prostate cancer following local therapy.
Localized therapy for prostate cancer is often curative; however, 20% to 30% of patients experience a recurrence. Men with biochemical recurrence (BCR) are typically identified following routine monitoring of prostatespecific antigen after treatment for localized disease. These patients exhibit no signs of prostate cancer. Initial evaluation attempts to determine whether the BCR is due to local recurrence or systemic disease. Depending on the type of initial local therapy, treatment options for local recurrence include salvage radiation therapy or salvage prostatectomy. If systemic recurrence is suspected, other options must balance the onset of metastatic disease with avoidance of overtreatment. The most common treatment is androgen deprivation therapy (ADT) via gonadotropinreleasing hormone agonists or antagonists. Because there are challenges associated with standard ADT, other treatment options are being investigated, including a number of natural products.


Acute subdural hematoma in patients on oral anticoagulant therapy: management and outcome.
OBJECTIVE Isolated acute subdural hematoma (aSDH) is increasing in older populations and so is the use of oral anticoagulant therapy (OAT). The dramatic increase of OAT-with direct oral anticoagulants (DOACs) as well as with conventional anticoagulants-is leading to changes in the care of patients who present with aSDH while receiving OAT. The purpose of this study was to determine the management and outcome of patients being treated with OAT at the time of aSDH presentation. METHODS In this single-center, retrospective study, the authors analyzed 116 consecutive cases involving patients with aSDH treated from January 2007 to June 2016. The following parameters were assessed: patient characteristics, admission status, anticoagulation status, perioperative management, comorbidities, clinical course, and outcome as determined at discharge and through 6 months of follow-up. Oral anticoagulants were classified as thrombocyte inhibitors, vitamin K antagonists, and DOACs. Patients were stratified based on which type of medication they were taking, and subgroup analyses were performed. Predictors of unfavorable outcome at discharge and follow-up were identified. RESULTS Of 116 patients, 74 (64%) had been following an OAT regimen at presentation with aSDH. The patients who were taking oral anticoagulants (OAT group) were significantly older (OR 12.5), more often comatose 24 hours postoperatively (OR 2.4), and more often had ≥ 4 comorbidities (OR 3.2) than patients who were not taking oral anticoagulants (no-OAT group). Accordingly, the rate of unfavorable outcome was significantly higher in patients in the OAT group, both at discharge (OR 2.3) and at follow-up (OR 2.2). Of the patients in the OAT group, 37.8% were taking a thrombocyte inhibitor, 54.1% a vitamin K antagonist, and 8.1% DOACs. In all cases, OAT was stopped on discovery of aSDH. For reversal of anticoagulation, patients who were taking a thrombocyte inhibitor received desmopressin 0.4 μg/kg, 1-2 g tranexamic acid, and preoperative transfusion with 2 units of platelets. Patients following other oral anticoagulant regimens received 50 IU/kg of prothrombin complex concentrates and 10 mg of vitamin K. There was no significant difference in the rebleeding rate between the OAT and no-OAT groups. The in-hospital mortality rate was significantly higher for patients who were taking a thrombocyte inhibitor (OR 3.3), whereas patients who were taking a vitamin K antagonist had a significantly higher 6-month mortality rate (OR 2.7). Patients taking DOACs showed a tendency toward unfavorable outcome, with higher mortality rates than patients on conventional OAT or patients in the vitamin K antagonist subgroup. Independent predictors for unfavorable outcome at discharge were comatose status 24 hours after surgery (OR 93.2), rebleeding (OR 9.8), respiratory disease (OR 4.1), and infection (OR 11.1) (Nagelkerke R2 = 0.684). Independent predictors for unfavorable outcome at follow-up were comatose status 24 hours after surgery (OR 12.7), rebleeding (OR 3.1), age ≥ 70 years (OR 3.1), and 6 or more comorbidities (OR 3.1, Nagelkerke R2 = 0.466). OAT itself was not an independent predictor for worse outcome. CONCLUSIONS An OAT regimen at the time of presentation with aSDH is associated with increased mortality rates and unfavorable outcome at discharge and follow-up. Thrombocyte inhibitor treatment was associated with increased short-term mortality, whereas vitamin K antagonist treatment was associated with increased long-term mortality. In particular, patients on DOACs were seriously affected, showing more unfavorable outcomes at discharge as well as at follow-up. The suggested medical treatment for aSDH in both OAT and no-OAT patients seems to be effective and reasonable, with comparable rebleeding and favorable outcome rates in the 2 groups. In addition, prior OAT is not a predictor for aSDH outcome.


Spousal Influence on Diabetes Self-care: Moderating Effects of Distress and Relationship Quality on Glycemic Control.
Spouses often attempt to influence patients' diabetes self-care. Spousal influence has been linked to beneficial health outcomes in some studies, but to negative outcomes in others. We aimed to clarify the conditions under which spousal influence impedes glycemic control in patients with type 2 diabetes. Spousal influence was hypothesized to associate with poorer glycemic control among patients with high diabetes distress and low relationship quality. Patients with type 2 diabetes and their spouses (N = 63 couples) completed self-report measures before patients initiated a 7-day period of continuous glucose monitoring. Mean glucose level and coefficient of variation (CV) were regressed on spousal influence, diabetes distress, relationship quality, and their two- and three-way interactions. The three-way interaction significantly predicted glucose variability, but not mean level. Results revealed a cross-over interaction between spousal influence and diabetes distress at high (but not low) levels of relationship quality, such that spousal influence was associated with less variability among patients with low distress, but more among those with high distress. Among patients with high distress and low relationship quality, a 1 SD increase in spousal influence predicted a difference roughly equivalent to the difference between the sample mean CV and a CV in the unstable glycemia range. This was the first study to examine moderators of the link between spousal influence and glycemic control in diabetes. A large effect was found for glucose variability, but not mean levels. These novel results highlight the importance of intimate relationships in diabetes management.


Determination of in vitro- and in vivo-formed DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline by capillary liquid chromatography/microelectrospray mass spectrometry.
Capillary liquid chromatography/microelectrospray mass spectrometry has been applied to the detection of deoxyribonucleoside adducts of the food-derived mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) from in vitro and in vivo sources. Constant neutral loss (CNL) and selective reaction monitoring (SRM) techniques with a triple-quadrupole mass spectrometer enabled sensitive and specific detection of IQ adducts in vitro and in animals. Detection of 1 adduct in 10(4) unmodified bases is achieved using CNL scanning detection, while the lower detection limits using SRM approach 1 adduct in 10(7) unmodified bases using 300 microg of DNA. The DNA adducts N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4, 5-f]quinoline (dG-C8-IQ) and 5-(deoxyguanosin-N(2)-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-N(2)-IQ) were detected in kidney tissues of chronically treated cynomolgus monkeys at levels and in proportions consistent with previously published (32)P-postlabeling data [Turesky, R. J., et al. (1996) Chem. Res. Toxicol. 9, 403-408]. Thus, capillary tandem LC/MS is a highly sensitive technique, which can be used to screen for DNA adducts in vivo.


Effect of chloroquine prophylaxis during pregnancy on maternal haematocrit.
Two controlled trials of chloroquine prophylaxis during pregnancy were performed, one in Burkina Faso in 1987, on all pregnant women, and the other in Cameroon in 1992, on primigravidae only. Maternal haematocrit at delivery was found to be significantly higher in those women who had received chloroquine than in those who had not, both in Burkina Faso (37.4% v. 36.5%; P = 0.01) and in Cameroon (34.8% v. 32.8%; P = 0.02). Anaemia, defined as an haematocrit of < 30%, was also less common in those treated with chloroquine (6.3% v. 8.5% in Burkina Faso and 8.3% v. 18.4% in Cameroon) but this difference was not significant in either country. A slight improvement in haematological status when prophylaxis is given has also been observed in similar studies performed in other tropical countries. The present results confirm the usefulness of targeting antimalarial prophylaxis at pregnant women. Such prophylaxis during the first pregnancy also increases birthweight.


The effects of intrinsic nitric oxide on cardiac neural regulation in cats.
In this study, we aimed to elucidate the effects of intrinsic nitric oxide (NO) on cardiac neural regulation. Twenty-two cats were anesthetized with 1.5% isoflurane and allocated to Group I (intact; n = 7), Group D (denervated baroreceptors and vagi; n = 8), or Group B (autonomic blockade with i.v. hexamethonium, propranolol, and atropine; n = 7). Cardiac sympathetic nerve activity (CSNA), mean arterial pressure (MAP), sinus heart rate (HR), and A-H and H-V intervals during pacing (150 bpm) were measured before and after i.v. administration of a NO synthase inhibitor, NG-nitro-L-arginine (L-NNA, 30 mg/kg) and after reversal with an excessive dose of L-arginine (300 mg/kg), before and during intermittent electrical stimulation of the posterior hypothalamus. L-NNA significantly increased MAP in Groups I and B, but not in Group D. L-NNA significantly decreased HR and lengthened A-H in Group I, but not in other groups. L-arginine further decreased HR and lengthened A-H unexpectedly. The reasons for these findings could not be determined in this study. L-NNA did not change CSNA. Hypothalamic stimulation did not potentiate L-NNA-induced changes in CSNA, hemodynamic variables, and atrioventricular conduction. In conclusion, intrinsic NO may modulate atrioventricular conduction and sinus rate through a vagal cholinergic, rather than a nonautonomic mechanism. Elucidating the roles of intrinsic nitric oxide (NO) on cardiac neural regulation is important. In intact, vagotomized, and baroreceptor-denervated or pharmacologically autonomic blockaded cats, an NO synthesis inhibitor was administered, and atrioventricular conduction and cardiac sympathetic neural discharge were measured. The results suggest a vagal cholinergic mechanism of intrinsic NO.


Association between central obesity, triglycerides and hypertension in a rural area in Brazil.
Hypertension represents a serious public health problem and is one of the most frequent causes of morbidity around the world. To estimate the prevalence of hypertension and its risk factors in a rural community located in the north-eastern state of Minas Gerais, Brazil. A cross-sectional study was carried out in 2004 in the Virgem das Graças Village, a rural community located the Jequitinhonha Valley. The sample consisted of 287 males and females aged between 18 to 88 years. Hypertension was defined according to Joint National Committee criteria (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg): subjects already receiving anti-hypertensive treatment were considered to be hypertensive. Bivariate analysis was performed to test the relationship between the independent variables and hypertension. Logistic regression was used to adjust for confounding and to identify interactions. The strength of association was measured using Odds Ratio (OR) and its 95% confidence intervals [CI (95%)]. The crude prevalence of hypertension was 47.0% [CI (95%): 41.1 - 53.0], the age-standardized prevalence was 43.2% [CI (95%): 35.7 - 50.7], while the schooling-standardized prevalence was 44.1% [CI (95%): 43.9 - 44.3]. Age, triglycerides, waist circumference and sex were found to be independent risk factors for hypertension according to multivariate analysis. The findings provide important evidence concerning the hypertension as a public health problem and its association with dyslipidemia and abdominal obesity in the rural area of Minas Gerais.


Prostate cancer mortality in the Finnish randomized screening trial.
Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality. A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0 ng/mL or 3.0 to 3.99 ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided. PC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P < .001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms. At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.