[New therapeutic strategies for community acquired pneumonia].
Community Acquired Pneumonia (CAP) is the most important infectious disease in Germany. In the acute phase, lethality is almost 10%, and in the six months follow up period following the acute infection, lethality is more than 15%. Problems with resistances had not been found in Germany, except for a decreasing susceptibility of S. pneumoniae against macrolides. The CRB-65 score allows a reliable discrimination between patients with a high and low risk of dying. The new S3 guideline for diagnosis and treatment of community acquired pneumonia recommends a risk adapted treatment. Low risk patients shall receive a monotherapy with e. g. amoxicillin, high risk patients should be treated with a broad spectrum combination therapy (beta-lactam and macrolide).


Toxic effects of colloidal nanosilver in zebrafish embryos.
A variety of consumer products containing silver nanoparticles (Ag NPs) are currently marketed. However, their safety for humans and for the environment has not yet been established and no standard method to assess their toxicity is currently available. The objective of this work was to develop an effective method to test Ag NP toxicity and to evaluate the effects of ion release and Ag NP size on a vertebrate model. To this aim, the zebrafish animal model was exposed to a solution of commercial nanosilver. While the exposure of embryos still surrounded by the chorion did not allow a definite estimation of the toxic effects exerted by the compound, the exposure for 48 h of 3-day-old zebrafish hatched embryos afforded a reliable evaluation of the effects of Ag NPs. The effects of the exposure were detected especially at molecular level; in fact, some selected genes expressed differentially after the exposure. The Ag NP toxic performance was due to the combined effect of Ag(+) ion release and Ag NP size. However, the effect of NP size was particularly detectable at the lowest concentration of nanosilver tested (0.01 mg l(-1)) and depended on the solubilization media. The results obtained indicate that in vivo toxicity studies of nanosilver should be performed with ad hoc methods (in this case using hatched embryos) that might be different depending on the type of nanosilver. Moreover, the addition of this compound to commercial products should take into consideration the Ag NP solubilization media.


Effects of 21-aminosteroid U74389F on skin-flap survival after secondary ischemia.
The effect of 21-aminosteroid, a lazaroid (U74389F), on tissue injury after secondary ischemia was evaluated in 3 x 5 cm island skin flaps in male Sprague-Dawley rats (n = 30). Primary ischemia was produced by arteriovenous occlusion for 1 hour. Eighteen hours later, secondary ischemia was inflicted by 4-hour venous occlusion. The treatment group received intravenous lazaroid (3 mg/kg) 30 minutes before the start of secondary ischemia. The control group received the same volume of citrate buffer vehicle using the same route and schedule. Skin-flap survival was an all-or-none phenomenon and assessed at 7 days after secondary ischemia. Malondialdehyde (MDA) content was measured to determine the occurrence of lipid peroxidation. Myeloperoxidase (MPO) activity was assayed to assess the degree of neutrophil infiltration. Treatment with this lazaroid significantly improved the survival rate from 0 percent (0 of 13) to 53 percent (9 of 17) (p < 0.01). Malondialdehyde content was 62 +/- 10 (mean +/- SEM, n = 4) pmol/mg dry weight in normal skin. Malondialdehyde increased by 3 times normal in the flaps destined to survive and by 13 times in the flaps destined to undergo necrosis (p < 0.001). Myeloperoxidase activity was negligible in normal skin. At the end of secondary ischemia, the flaps destined to survive exhibited a high myeloperoxidase activity. The flaps destined to necrosis showed the enzyme activity 2.2 times more than surviving flaps (p < 0.01). The results suggest that the lazaroid U74389F may improve survival by attenuating neutrophil infiltration and by reducing lipid peroxidation.


Human rights of an embryo.
Spontaneous ethical views very often spring just from feelings. But an ethical standpoint of any lasting value cannot be based just upon feelings. Relevant facts and values are indispensable. The purpose of the article is to draw the attention to the set of values that is enshrined in the Universal Declaration of Human Rights, particularly the values of human life, human dignity, human liberty, human physical integrity and the brotherhood of man. More generally recognized values are difficult to find. The usefulness of them as criteria in ethical contexts is tested by applying them to a judging pro and con of research on human embryos. The testing is performed against the background of the report of the Warnock Committee.


Knee Joint Rescue in a Traumatic Amputation With Coverage by a Fillet-Free Flap From the Amputated Leg.
Traumatic amputation is a severe injury that requires urgent surgical care. A fillet-free flap from the amputated limb is the most conservative way to ensure proper coverage of the stump when replantation is not possible. We report the case of a male patient who suffered from a traumatic limb amputation in a motorcycle accident. A free fillet flap from the posterior compartment of the leg carrying the posterior tibial pedicle, the soleus muscle, and skin tissue harvested from the amputated limb was performed to cover the amputation stump and thus allow preservation of the knee joint. In our case report, the patient conserved almost maximal knee joint range of motion (130°). He regained the ability to walk only two months after the initial trauma. Prosthetic fitting occurred quickly and without any particular issues throughout the process. Regarding quality of life, after one year, our patient had a five-level EQ-5D version (EQ-5D-5L) score of 21,221, and his 36-Item Short Form Survey (SF-36) score was divided between the five components in 85 points in physical functioning, 100 points in role limitations due to physical health, 100 points in role limitations due to emotional problems, 50 points in energy/fatigue, 68 points in emotional well-being, 75 points in social functioning, 45 points in pain, and 95 points in general health. This technique helped provide good coverage of the stump while preserving a functional knee joint, allowing for effective prosthetic fitting in the future and therefore optimizing our patient's quality of life.


Kinetic evaluation of beta-neoendorphin hydrolysis by the somatic and testicular isozymes of human angiotensin-converting enzyme.
Angiotensin-converting enzyme (ACE) has both somatic and testicular isozymes, the former possessing two catalytically active domains, amino-terminal and carboxyl-terminal, while the latter has only the carboxyl-terminal one. We compared hydrolysis processes of the nonapeptide beta-neoendorphin by the two isozymes of human ACE. Both isozymes hydrolyzed the peptide to Tyr1-Gly2-Gly3 by the sequential removal of carboxyl-terminal dipeptides in three consecutive steps. The rate constant values for the second step, conversion of beta-neoendorphin1-7 to Leu-enkephalin, by the somatic isozyme in the presence of 10 or 200 mM NaCl were 4-fold higher than those for the first step, conversion of beta-neoendorphin1-9 to beta-neoendorphin1-7. The k(cat) values of the somatic isozyme for beta-neoendorphin1-7 were 2-fold higher than those for beta-neoendorphin1-9, indicating that beta-neoendorphin1-7 is more rapidly hydrolyzed than beta-neoendorphin1-9. The rate constant value for the second step at 10 mM NaCl was 5-fold higher than that for the testicular isozyme. Similar extent of difference was also observed in k(cat) values for beta-neoendorphin1-7 between the two isozymes. These results suggest that the amino-terminal domain of the somatic isozyme mainly contributes to the conversion of beta-neoendorphin1-7 to Leu-enkephalin at a low NaCl concentration. Optimal chloride concentrations for the individual steps of beta-neoendorphin1-9 hydrolysis differed between the two isozymes.


Leptin and melatonin's effects on OVX rodents' bone metabolism.
This study aims to examine the effects of leptin and melatonin intervention on bone metabolism in ovariectomize (OVX) rodents, as well as their potential mechanisms of action. Prepare an OVX model of osteoporosis in rodents and validate the model by collecting bilateral tibia samples for Micro-CT scanning and histological analysis. A control group of normal size, the OVX group, the OVX+Sema4D (Semaphorin 4D) group, the OVX+Sema4D+Leptin group, the OVX+Sema4D+ Melatonin(MT) group and the OVX+Sema4D+Leptin+ MT group were the experimental groups. Adenovirus vector construction and tibial medullary injection validation were conducted in accordance with the aforementioned experimental groups. Four groups of rats were injected with the Sema4D overexpression adenovirus vector into the tibial medullary cavity, and two groups were injected with the Leptin overexpression adenovirus vector. The repair of osteoporosis was observed using micro-CT and histological analysis. Immunohistochemical detection of bone morphogenetic protein-2 (BMP-2) expression in bone tissue was employed to ascertain the amount of osteoclasts in the upper tibial metaphysis, utilizing TRAP(tartrate-resistant acid phosphatase) staining. Increased levels of BV/TV, Tb.N, BMD, and BMC were seen in the OVX+ Sema4D+Leptin, OVX+ Sema4D+MT, and OVX+ Sema4D+Leptin+ MT groups compared to the OVX group, whereas Tb. Sp levels were lowered. When compared to the Sema4D overexpression group, the trabecular bone structure of the OVX + Sema4D + Leptin, OVX + Sema4D + MT, and OVX + Sema4D + Leptin + MT groups is largely intact, tends to be closer, and the amount of trabecular bone increases. The OVX + Sema4D + Leptin + MT group in particular.The expression of BMP-2 was dramatically upregulated (p<0.05), the number of TRAP-stained osteoclasts was significantly reduced (p<0.05), and BALP(bone-derived alkaline phosphatase) and TRAP-5b(tartrate-resistant acid phosphatase-5b) activities were significantly downregulated (p<0.05). In rats with osteoporosis, leptin and melatonin can be seen to augment the trabecular microstructure of the bone, augment bone growth, diminish trabecular harm, and mend the bone. The combined effect is more powerful.


The effect of personality on measures of quality of life related to vision in glaucoma patients.
To determine the effect of personality on vision-specific health-related quality of life (HRQoL). Based on power calculations, 148 individuals diagnosed as having glaucoma or ocular hypertension, without ocular comorbidity, were selected using criteria that included age over 30, no recent or upcoming surgery, the absence of a diagnosis of clinical depression or any other psychiatric illness. Qualifying participants completed the 25-Item National Eye Institute's Visual Function Questionnaire (VFQ), the Neuroticism, Extraversion and Openness Personality Inventory Revised (NEO PI-R) and the 15-Item Geriatric Depression Scale (GDS-15), and provided information regarding their demographic characteristics and past medical history. Each patient also underwent an ocular examination. Data analysis was conducted to determine the relationship between NEO PI-R personality profiles and VFQ scoring, while controlling for the effects of a range of demographic, psychiatric, past medical and clinical ophthalmic variables. Multivariate analysis indicated that after controlling for a range of covariates, three out of five NEO PI-R personality domains shared statistically significant associations with a variety of VFQ total and subscale score measurements. Normal variations in personality characteristics influence how patients report their vision-specific HRQoL.


Log-stable laws as asymptotic solutions to a fragmentation equation: application to the distribution of droplets in a high Weber-number spray.
In this paper, it will be shown that "totally skewed to the left" log-stable distributions are suitable asymptotic solutions to a fragmentation equation. This result generalizes Kolmogorov's work on log-normal distribution for the drops' size number distribution of particles under pulverization. Indeed, Kolmogorov's discrete process is extended to a continuous time Markov process for the volume distribution instead of the number distribution. New hypotheses are then introduced which lead to log-stable distributions as asymptotic solutions of the fragmentation equation. Log-stable laws are then used to fit experimental probability distribution function (pdf) of Simmons and Hanratty measuring drop sizes in a horizontal annular gas-liquid flow at high Weber number [Int. J. Multiphase Flow 27, 861 (2001)]]. Log-stable pdf better fits to the experimental pdf than usual empirical spray pdf and especially, because of the heavy tail of the associated stable distribution, in the small drops part of the distribution.


Chronic myeloid leukemia: current status and controversies.
Until recently, the standard treatment for newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase who were not eligible for allogeneic stem cell transplant was interferon-alfa alone or in combination with low-dose cytarabine. Moreover, about 20% to 25% of patients who were relatively young and had suitable HLA-matched donors have in recent years been offered treatment by allogeneic stem cell transplantation, a procedure that can cure CML but is associated with an appreciable risk of morbidity and mortality. However, following the recognition in the 1980s that the p210 oncoprotein encoded by the BCR-ABL fusion gene on the Philadelphia chromosome had greatly enhanced tyrosine kinase activity and was probably the initiating event in the chronic phase of CML, much effort was directed toward development of drugs that would selectively inhibit this kinase activity. In 1998 these efforts culminated in the first clinical use of imatinib mesylate (Gleevec), which has since been shown to produce impressive results in treatment of patients with CML in chronic phase. In previously untreated patients, the incidence of complete cytogenetic responses exceeds 80%, and the majority of responses appear thus far to be durable. Imatinib also proved active in patients with accelerated phase and blastic phase disease, but in most of these cases, the benefits have been relatively short-lived. The advent of imatinib has thus necessitated a fundamental reappraisal of the approach to the initial management of CML.


Quality of Life After Treatment for Pelvic Organ Prolapse: Vaginal Pessary versus Surgery.
Pelvic organ prolapse (POP) is quite common and has an impact on quality of life (QoL). The evaluation of QoL after treatment for prolapse is important. The objective was to compare patient's prolapse symptoms, functional outcomes, and quality of life between pessary and surgery using standardized questionnaires at 1 and 6 months after treatment. We conducted a prospective study including women with symptomatic POP who chose pessary or surgery as the first-line treatment. We evaluated QoL using the International Consultation on Incontinence Questionnaire-Vaginal Symptoms and Prolapse Quality of Life questionnaires. Seventy-two participants were enrolled, with 36 in each group. Body mass index, menopausal status, marital status, number of vaginal deliveries, and stage of pelvic organ prolapse were not significantly different between the groups. At 1 and 6 months after treatment, participants in both groups reported significant improvement in prolapse symptoms, functional outcomes, and overall quality of life. At 1 month after treatment, absolute changes in vaginal symptom scores in the pessary and surgery groups were -16.67 and -19.03, respectively (p > 0.05); at 6 months, the absolute changes were -19.21 and -19.25, respectively (p > 0.05). Significant improvement was only found in role limitation and physical and social domains at both follow-up times after surgery. At 1 and 6 month(s) after treatment, women with symptomatic POP reported substantial improvement in prolapse symptoms and functional outcomes when treated with pessary or surgical correction.


Resonant drift of two-armed spirals by a periodic advective field and periodic modulation of excitability.
The drift behavior of two-armed spirals induced by periodic advective field and periodic modulation of excitability is investigated. It is shown that the two-armed spirals controlled by periodic advective field and periodic modulation of excitability drift in completely different ways. For periodic advective field, the two tips of the two-armed spiral drift in the same direction and the two-armed spiral is stable. While for periodic modulation of excitability, the two tips drift in the opposite direction and the two-armed spiral splits into two single-armed spirals. Analytical results based on a kinematic theory of rotating spirals in weakly excitable media are consistent with the numerical results.


Lens-free all-fiber probe with an optimized output beam for optical coherence tomography.
A high-efficiency lensless all-fiber probe for optical coherence tomography (OCT) is presented. The probe is composed of a segment of large-core multimode fiber (MMF), a segment of tapered MMF, and a length of single-mode fiber (SMF). A controllable output beam can be designed by a simple adjustment of its probe structure parameters (PSPs), instead of the selection of fibers with different optical parameters. A side-view probe with a diameter of 340 μm and a rigid length of 6.37 mm was fabricated, which provides an effective imaging range of ∼0.6 mm with a full width at half-maximum beam diameter of less than 30 μm. The insertion loss of the probe was measured to be 0.81 dB, ensuring a high sensitivity of 102.25 dB. Satisfactory images were obtained by the probe-based OCT system, demonstrating the feasibility of the probe for endoscopic OCT applications.


Gender differences in clinical characteristics, medical management, risk factor control, and long-term outcome of patients with stable coronary artery disease: from the CORONOR registry.
Conflicting information exists about whether sex differences modulate outcome in patients with coronary artery disease (CAD). Our aim was to analyze baseline characteristics, medical management, risk factor control, and long-term outcome according to gender in patients with stable CAD. We analyzed data from the contemporary multicenter CORONOR registry, which included 4184 consecutive outpatients with stable CAD. Follow-up was performed at 5 years with adjudication of clinical events. There were 3252 (77.7%) men and 932 (22.3%) women. Women were older than men, more likely to have hypertension, and less likely to smoke. They had more frequent angina but less frequent multivessel CAD. Evidence-based medications were widely used with only few differences according to gender. Women had a poorer control of cardiovascular risk with higher systolic blood pressure and LDL-cholesterol. The composite endpoint - cardiovascular death, myocardial infarction, or ischemic stroke - occurred in 536 patients. When adjusted for baseline characteristics, five-year outcomes were similar for women and men for the composite endpoint (Hazard ratio [95% confidence interval]: 1.03 [0.81-1.31], P=0.817). In contemporary practice, women with stable CAD had a poorer control of cardiovascular risk. However, at 5-year follow-up, cardiovascular outcomes were similar for both genders.


Changes in erythrocyte enzyme activities during erythrocyte aging in alcoholism.
Aldehyde dehydrogenase, glucose-6-phosphate dehydrogenase, and pyruvate kinase activities were determined in erythrocytes of various ages, separated by Percoll gradient centrifugation, in 13 alcoholic patients and eight control subjects. The total erythrocyte activities of all three enzymes were not affected by alcoholism, however, the youngest cells of alcoholics had a decreased aldehyde dehydrogenase activity, while both glucose-6-phosphate dehydrogenase and pyruvate kinase activities were increased. The depression of aldehyde dehydrogenase activity not only persisted, but became more marked after 2 weeks of abstinence, while the enhanced activities of the two other enzymes returned to normal. These observations suggest that chronic alcohol ingestion suppresses aldehyde dehydrogenase in the bone marrow, while it enhances other erythrocytic enzymes.


The Transspinal Canal Screwing Technique for Atlantoaxial Anomalies: A Technical Note and 2 Case Reports.
It is difficult to treat atlantoaxial instability in patients with a high-riding vertebral artery or anomalies of the craniocervical junction. We report 2 successful cases in which the transspinal canal screwing technique was used because of difficulties performing conventional fixation methods. Case 1: A 78-year-old woman suffered from progressive myelopathy due to severe spinal cord compression with a congenital anomaly of the craniovertebral junction. Bilateral transspinal canal screws from the axis body with spondylolisthesis to the dens were inserted by retracting the dural sac medially after foramen magnum decompression and cervical laminoplasty. Case 2: A 20-year-old man with a spinal deformity due to Loeys-Dietz syndrome presented to our hospital for treatment of syringomyelia. He had no obvious neurological deficits, but spinal cord compression due to right atlantoaxial rotating dislocation was observed. A screw was inserted from the vertebral body of the axis to the right lateral mass of the atlas via the spinal canal after laminectomy of the atlas. The transspinal canal screwing technique is useful for treating atlantoaxial instability in cases where other fixation methods are difficult.


Ectopia cordis with a double outlet right ventricle, large ventricular septal defect, malposed great arteries and left ventricular hypoplasia.
Ectopia cordis, defined as partial or complete displacement of the heart outside of the thoracic cavity, is a rare congenital malformation. If not surgically corrected during the early years of life, ectopia cordis can prove to be a fatal abnormality. However, due to the presence of multiple intracardiac and extracardiac malformations, a corrective surgery might not always be successful. The pathology of ectopia cordis with a double outlet right ventricle, large ventricular septal defect, malposed great arteries and left ventricular hypoplasia is discussed, highlighting the complexities involved in such a rare disorder.


[Lipomatous hypertrophy of the cardiac interatrial septum].
Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare lesion of unknown origin usually diagnosed as an incidental finding during autopsy. It can be associated with supraventricular arrhythmias, venous return obstruction and sudden cardiac death. Five necropsy cases (4 females, 1 male) of LHIS were encountered during the last 31 years; only one case from this series was diagnosed ante mortem. The patients' mean age was 68 years; their mean BMI was 28.4. The mean size of the lesion was 31 mm. In three patients the LHIS was asymptomatic, two patients experienced relapsing multifocal atrial tachycardia and sick sinus syndrome, respectively. Histologically, all cases consisted of a mixture of mature and brown adipose tissue with foci of cardiomyocytes. For a pathologist the knowledge of LHIS is important because of an increasing possibility of its ante mortem diagnosis by imaging methods with a following endomyocardial biopsy, and also because it may appear as a cause of sudden cardiac death.


Theoretical predictions of the initial decomposition steps of dimethylnitramine.
The structures and energies of the reactants, products, and transition states of the initial steps in the gas-phase decomposition of dimethylnitramine (DMNA) have been determined by quantum chemical calculations at the B3LYP density-functional theory, MP2, and G2 levels. The pathways considered are NO2 elimination, HONO elimination, and nitro-nitrite rearrangement. The NO2 elimination is predicted to be the main channel of the gas-phase decomposition of DMNA in accord with experiment. The values of the Arrhenius parameters, log A=16.6+/-0.5 and Ea=40.0+/-0.6 kcal/mol, for the N-NO2 bond-fission reaction were obtained using a canonical variational theory with B3LYP energies and frequencies. The HONO-elimination channel has the next lowest activation energy of 44.7+/-0.5 kcal/mol (log A=13.6+/-0.5) and is characterized by a five-member transition-state configuration in which a hydrogen atom from one of the methyl groups is transferred to an oxygen atom of NO2. Tunneling contributions to the rate of this reaction have been estimated. The nitro-nitrite rearrangement reaction occurs via a transition state in which both oxygen atoms of NO2 are loosely bound to the central nitrogen atom, for which Rice-Ramsperger-Kassel-Marcus theory predicts log A=14.4+/-0.6 and Ea=54.1+/-0.8 kcal/mol.


Effects of a physical education intervention on attention and inhibitory control in Ecuadorian children with intellectual disabilities.
Background: Studies on physical activity interventions indicated a facilitative effect on cognitive performance in persons with intellectual disabilities; however, research is scarce, especially in low/middle-income countries. Aim: We explored the effects of a 6-week enriched physical education program on inhibitory control and attention functions in Ecuadorian children with intellectual disabilities. Methods: Thirty children with mild intellectual disabilities (10-14 years old) were randomly assigned to an intervention or control group. Before and after the intervention, attention and inhibitory control were measured using computer-based nonverbal tasks. Results: The findings showed significantly more accurate and faster responses in the vigilance task in the intervention group than in the controls. There were no significant intervention-related changes in inhibitory control; however, there were more prominent accuracy tendencies toward improvement in the intervention group. Conclusions: Results provide evidence of the potential of physical activity programs to enhance attention in this population, which could serve as a mediator for inhibitory control.


TrkC-miR2 regulates TGFβ signaling pathway through targeting of SMAD3 transcript.
TrkC, neurotrophin receptor, functions inside and outside of the nervous system and has a crucial effect on the regulation of cardiovascular formation. Recently, we introduced TrkC-miR2 as a novel microRNA located in TrkC gene, which is a regulator of the Wnt signaling pathway. Here, we presented a lot of evidence showing that TrkC-miR2 also regulates the transforming growth factor-beta (TGFβ) signaling pathway. Bioinformatics studies predicted SMAD3 as one of the bona fide TrkC-miR2 target genes. Quantitative reverse transcription PCR (RT-qPCR), Western blot analysis, and dual luciferase assay analysis confirmed that SMAD3 is targeted by TrkC-miR2. On the other hand, overexpression of TrkC-miR2 in cardiosphere-derived cells (CDCs) rendered downregulation of TGFβR1, TGFβR2, and SMAD7 detected by RT-qPCR. Consistently, an inverse correlation of expression between TrkC-miR2 and SMAD3 genes was detected during the course of CDC differentiation, and also during the course of human embryonic stem cells differentiation to cardiomyocytes. Overall, we conclude that TrkC-miR2 downregulates the expression of SMAD3 and potentially regulates the TGFβ signaling pathway. Knowing its approved effect on Wnt signaling, TrkC-miR2 here is introduced as a common regulator of both the Wnt and TGFβ signaling pathways. Therefore, it may be a potential key element in controlling both of these signaling pathways in cell processes like colorectal cancer and cardiogenesis.


Stereopsis before and after Inferior Oblique Weakening Surgery.
To analyze stereopsis change before and after inferior oblique weakening surgery. We retrospectively reviewed the medical records of 31 patients who had undergone inferior oblique weakening surgery. The factors analyzed included sex, age at surgery, preoperative and postoperative visual acuity (VA), time from first detection to surgery, degree of inferior oblique overaction (IOOA), primary/secondary IOOA, exotropia/hypertropia, bilaterality, and type of surgery. Eighteen patients with a mean age 7.3 ± 3.1 years exhibited stereopsis of 60 arc seconds or better before surgery and 17 had stereopsis better than 60 arc seconds after surgery. Postoperatively, stereopsis improved in 13 patients and deteriorated in 9. Better preoperative VA and the absence of superior oblique underaction were associated with better preoperative stereopsis. Better preoperative VA, postoperative VA, and the presence of head tilt were associated with better postoperative stereopsis. Unilateral inferior oblique weakening surgery and accompanying hypertropia were associated with improved stereopsis, while the absence of hypertropia was associated with deteriorated stereopsis. In this retrospective study, 58.1% of patients tended to have bifoveal fixation. When a vertical deviation is present in the primary position due to unilateral IOOA, IO weakening surgery can be expected to improve binocular function.


The release of trace elements in the process of coal coking.
In order to assess the penetration of individual trace elements into the air through their release in the coal coking process, it is necessary to determine the loss of these elements by comparing their contents in the charge coal and in coke obtained. The present research covered four coke oven batteries differing in age, technology, and technical equipment. By using mercury analyzer MA-2 and the method of ICP MS As, Be, Cd, Co, Hg, Mn, Ni, Se, Sr, Tl, V, and Zn were determined in samples of charge coal and yielded coke. Basing on the analyses results, the release coefficients of selected elements were determined. Their values ranged from 0.5 to 94%. High volatility of cadmium, mercury, and thallium was confirmed. The tests have shown that although the results refer to the selected case studies, it may be concluded that the air purity is affected by controlled emission occurring when coke oven batteries are fired by crude coke oven gas. Fugitive emission of the trace elements investigated, occurring due to coke oven leaks and openings, is small and, is not a real threat to the environment except mercury.


QTc interval prolongation associated with intravenous methadone.
Numerous medications prolong the rate-corrected QT (QTc) interval and induce arrhythmias by blocking ionic current through cardiac potassium channels composed of subunits expressed by the human ether-a-go-go-related gene (HERG). Recent reports suggest that high doses of methadone cause torsades de pointes. To date, no controlled study has described an association between methadone and QTc prolongation. The only commercial formulation of parenteral methadone available in the United States contains the preservative chlorobutanol. The objectives of this study are to determine: (1) whether the administration of intravenous (i.v.) methadone causes QTc prolongation in humans; (2) whether methadone and/or chlorobutanol block cardiac HERG potassium currents (IHERG) in vitro. Over 20 months, we identified every inpatient with at least one electrocardiogram (ECG) performed on i.v. methadone. For each patient, we measured QTc intervals for every available ECG performed on and off i.v. methadone. Concurrent methadone doses were also recorded. Similar data were collected for a separate group of inpatients treated with i.v. morphine. In a separate set of experiments IHERG was evaluated in transfected human embryonic kidney cells exposed to increasing concentrations of methadone, chlorobutanol, and the two in combination. Mean difference (+/- standard error) per patient in QTc intervals on and off methadone was 41.7 (+/- 7.8)ms, p<0.0001. Mean difference in QTc intervals on and off morphine was 9.0 (+/- 6.1)ms, p=0.15. The approximately linear relationship between QTc measurements and log-dose of methadone was significant (p<0.0001). Methadone and chlorobutanol independently block IHERG in a concentration-dependent manner with IC50 values of 20 +/- 2 microM and 4.4 +/- 0.3 mM, respectively. Chlorobutanol potentiates methadone's ability to block IHERG. Methadone in combination with chlorobutanol is associated with QTc interval prolongation. Our data strongly suggest that methadone in combination with chlorobutanol is associated with QTc interval prolongation.


Making the case for objective performance metrics in newborn screening by tandem mass spectrometry.
The expansion of newborn screening programs to include multiplex testing by tandem mass spectrometry requires understanding and close monitoring of performance metrics. This is not done consistently because of lack of defined targets, and interlaboratory comparison is almost nonexistent. Between July 2004 and April 2006 (N=176,185 cases), the overall performance metrics of the Minnesota program, limited to MS/MS testing, were as follows: detection rate 1:1,816, positive predictive value 37% (54% in 2006 till date), and false positive rate 0.09%. The repeat rate and the proportion of cases with abnormal findings actually been reported are new metrics proposed here as an objective mean to express the overall noise in a program, where noise is defined as the total number of abnormal results obtained using a given set of cut-off values. On the basis of our experience, we propose the following targets as evidence of adequate analytical and postanalytical performance: detection rate 1:3,000 or higher, positive predictive value>20%, and false positive rate<0.3%.


On the Coordination Chemistry of the lanthanum(III) Nitrate Salt in EAN/MeOH Mixtures.
A thorough structural characterization of the La(NO3)3 salt dissolved into several mixtures of ethyl ammonium nitrate (EAN) and methanol (MeOH) with EAN molar fraction χEAN ranging from 0 to 1 has been carried out by combining molecular dynamics (MD) and X-ray absorption spectroscopy (XAS). The XAS and MD results show that changes take place in the La3+ first solvation shell when moving from pure MeOH to pure EAN. With increasing the ionic liquid content of the mixture, the La3+ first-shell complex progressively loses MeOH molecules to accommodate more and more nitrate anions. Except in pure EAN, the La3+ ion is always able to coordinate both MeOH and nitrate anions, with a ratio between the two ligands that changes continuously in the entire concentration range. When moving from pure MeOH to pure EAN, the La3+ first solvation shell passes from a 10-fold bicapped square antiprism geometry where all the nitrate anions act only as monodentate ligands to a 12-coordinated icosahedral structure in pure EAN where the nitrate anions bind the La3+ cation both in mono- and bidentate modes. The La3+ solvation structure formed in the MeOH/EAN mixtures shows a great adaptability to changes in the composition, allowing the system to reach the ideal compromise among all of the different interactions that take place into it.


Is the common cold a clinical entity or a cultural concept?
Common cold is the most common infectious disease of mankind and the term is widely used in the clinical literature as though it were a defined clinical syndrome. Clinical studies on this syndrome often use elaborate symptom scoring systems to diagnose a common cold. The symptom scores are based on a study conducted over 50 years ago to retrospectively diagnose experimental cold and this method cannot be applied to diagnosis of common cold in the community. Diagnosis of the common cold by virology is not feasible because of the number of viruses and the variability in the disease states caused by the viruses. Because of the familiarity of subjects with common cold and the variability in symptomatology it seems a more reasonable approach to use self-diagnosis of common cold for clinical research studies and accept that the common cold is a cultural concept and not a clinical entity.


Vapor phase tri-methyl-indium seeding system suitable for high temperature spectroscopy and thermometry.
Tri-methyl-indium (TMI) is used as an indium transport molecule to introduce indium atoms to reactive hot gas flows/combustion environments for spectroscopic diagnostics. A seeding system was constructed to allow the addition of an inert TMI laden carrier gas into an air/fuel mixture burning consequently on a burner. The amount of the seeded TMI in the carrier gas can be readily varied by controlling the vapor pressure through the temperature of the container. The seeding process was calibrated using the fluorescent emission intensity from the indium 6(2)S1/2 → 5(2)P1/2 and 6(2)S1/2 → 5(2)P3/2 transitions as a function of the calculated TMI seeding concentration over a range of 2-45 ppm. The response was found to be linear over the range 3-22.5 ppm; at concentrations above 25 ppm there is a loss of linearity attributable to self-absorption or loss of saturation of TMI vapor pressure in the carrier gas flow. When TMI was introduced into a post-combustion environment via an inert carrier gas, molecular transition from InH and InOH radicals were observed in the flame emission spectrum. Combined laser-induced fluorescence and absorption spectroscopy were applied to detect indium atoms in the TMI seeded flame and the measured atomic indium concentration was found to be at the ppm level. This method of seeding organometallic vapor like TMI to a reactive gas flow demonstrates the feasibility for quantitative spectroscopic investigations that may be applicable in various fields, e.g., chemical vapor deposition applications or temperature measurement in flames with two-line atomic fluorescence.


Mouse model for sublethal Leptospira interrogans infection.
Although Leptospira can infect a wide range of mammalian species, most studies have been conducted in golden Syrian hamsters, a species particularly sensitive to acute disease. Chronic disease has been well characterized in the rat, one of the natural reservoir hosts. Studies in another asymptomatic reservoir host, the mouse, have occasionally been done and have limited infection to mice younger than 6 weeks of age. We analyzed the outcome of sublethal infection of C3H/HeJ mice older than age 10 weeks with Leptospira interrogans serovar Copenhageni. Infection led to bloodstream dissemination of Leptospira, which was followed by urinary shedding, body weight loss, hypothermia, and colonization of the kidney by live spirochetes 2 weeks after infection. In addition, Leptospira dissemination triggered inflammation in the kidney but not in the liver or lung, as determined by increased levels of mRNA transcripts for the keratinocyte-derived chemokine, RANTES, macrophage inflammatory protein 2, tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, interleukin-6, and gamma interferon in kidney tissue. The acquired humoral response to Leptospira infection led to the production of IgG mainly of the IgG1 subtype. Flow cytometric analysis of splenocytes from infected mice revealed that cellular expansion was primarily due to an increase in the levels of CD4(+) and double-negative T cells (not CD8(+) cells) and that CD4(+) T cells acquired a CD44(high) CD62L(low) effector phenotype not accompanied by increases in memory T cells. A mouse model for sublethal Leptospira infection allows understanding of the bacterial and host factors that lead to immune evasion, which can result in acute or chronic disease or resistance to infection (protection).


How does economic inequality shape conspiracy theories? Empirical evidence from China.
Conspiracy theories tend to be prevalent, particularly in societies with high economic inequality. However, few studies have examined the relationship between economic inequality and belief in conspiracy theories. We propose that economic inequality leads people to believe conspiracy theories about economically advantaged groups (i.e., upwards conspiracy theories) and that moral evaluations of those groups mediate this relationship. Study 1 (N = 300) found support for these ideas in a survey among Chinese residents. Study 2 (N = 160) manipulated participants' perceptions of economic inequality in a virtual society. The manipulation shaped moral evaluations of economically advantaged groups, and conspiracy beliefs, in the predicted manner. In Study 3 (N = 191) and Study 4 (N = 210), we experimentally manipulated participants' perceptions of economic inequality in real Chinese society and replicated the results of Study 2. In addition, in Study 4, we find that economic inequality predicts belief in conspiracy theories about economically disadvantaged groups (i.e., downward conspiracy theories), which was mediated by anomie. We conclude that perceived economic inequality predicts conspiracy theories about economically advantaged groups and that moral evaluations account for this effect. Also, upward and downward conspiracy theory beliefs are associated with different psychological processes.


Third left pulmonary vein with abnormal return associated with arteriovenous fistula.
Anomalies of pulmonary veins are uncommon and vary widely in their anatomic spectrum and clinical presentation. A 20-year-old woman with complaints of effort-induced dyspnea and easy fatigability was diagnosed with a third left pulmonary vein with abnormal return and arteriovenous fistula accompanied by a secundum atrial septal defect (ASD). Complete surgical repair was performed by ASD closure with a pericardial patch and triple ligation of the left vertical vein and associated third pulmonary vein. The patient was discharged on the seventh postoperative day in good health. Her last control examination was performed in the second postoperative year, revealing normal echocardiographic findings with an excellent clinical course.


Pediatric SARS, H1N1, MERS, EVALI, and Now Coronavirus Disease (COVID-19) Pneumonia: What Radiologists Need to Know.
OBJECTIVE. The purpose of this article is to review new pediatric lung disorders-including disorders that have occurred in recent years years such as severe acute respiratory syndrome (SARS), swine-origin influenza A (H1N1), Middle East respiratory syndrome (MERS), e-cigarette or vaping product use-associated lung injury (EVALI), and coronavirus disease (COVID-19) pneumonia-to enhance understanding of the characteristic imaging findings. CONCLUSION. Although the clinical symptoms of SARS, H1N1, MERS, EVALI, and COVID-19 pneumonia in pediatric patients may be nonspecific, some characteristic imaging findings have emerged or are currently emerging. It is essential for radiologists to have a clear understanding of the characteristic imaging appearances of these lung disorders in pediatric patients to ensure optimal patient care.


Effect of a parenting education program on girls' life satisfaction in governmental guidance schools of Shiraz.
One of the main determinants of adolescents' life satisfaction is parenting skills. Due to the lack of educational trials in this field, this research was done to evaluate the effect of a parenting education program on girls' life satisfaction in governmental guidance schools of Shiraz. This study is an educational randomized controlled trial. At first, 152 female students in 2nd grade of governmental guidance schools and 304 parents (152 mother and 152 father) were selected by multistage random cluster sampling method. Then, they were categorized into experimental and control groups. Before and after the intervention, data were collected from two groups using multidimensional students' life satisfaction scale with stability (Cronbach's alpha=0.89), test-retest and correlation coefficient (r=0.70). Educational intervention for parents was performed in the experimental group through presentations with question and answer, discussion in small groups and distribution of educational booklets in 5 volumes. Finally, the data were analyzed using SPSS 14 and through Mann-Whitney test, Chi-square test, Fisher's Exact test, Wilcoxon test. Before the intervention, the experimental and control groups did not show a statistically significant difference based on the demographic variables. Thetotal of life satisfaction scores and also its subscales in the experimental and controlgroup, before and six weeks afterthe educational interventiondid showstatisticallysignificant difference (p<0.001). The scores of differences (pre-test/post-test) in total life satisfaction between the experimental and control groups were statistically significant difference (p<0.001). According to low scores of the students in the pre-test, especially in the control group which didn't undergo any educational program, holding scheduled educational intervention is necessary. This study not only supports the effectiveness of educational intervention but also recommends further educational research to develop knowledge regarding patterns of parenting education.


[Pollutant production and discharge from livestock and poultry industries and land carrying capacity in Zhejiang Province].
Based on the investigation of pollutant production and discharge from a typical scale pig farm in Zhejiang Province at three pig growth stages (piglets, fattening pigs, and sows) in the autumn and winter 2007 and the spring and summer 2008, the coefficients of pollutant production and discharge from the pigs as well as the total annual pollutant production and discharge from the farm were estimated. In the meantime, the annual application amount of animal manure to the farmlands in Zhejiang Province was estimated by using these coefficients and the livestock and poultry inventories in Zhejiang Province in 2007. It was estimated that the total amount of applied animal manure in the Province in 2007 was 2106.8 x 10(4) t x a(-1), containing 13.57 x 10(4) t x a(-1) of N, 6.7 x 10(4) t x a(-1) of P, 0.11 x 10(4) t x a(-1) of Cu, and 0.20 x 10(4) t x a(-1) of Zn. The pig-manure-equivalent farmland carrying capacity in the Province was 16.66 t x hm(-2) a(-1), and the average alarm limit was 0. 37. The application of animal manure in some areas of Zhejiang Province had exceeded the alarm limit for the land carrying capacity, and made a potential environmental threat.


Feedback between motion and sensation provides nonlinear boost in run-and-tumble navigation.
Many organisms navigate gradients by alternating straight motions (runs) with random reorientations (tumbles), transiently suppressing tumbles whenever attractant signal increases. This induces a functional coupling between movement and sensation, since tumbling probability is controlled by the internal state of the organism which, in turn, depends on previous signal levels. Although a negative feedback tends to maintain this internal state close to adapted levels, positive feedback can arise when motion up the gradient reduces tumbling probability, further boosting drift up the gradient. Importantly, such positive feedback can drive large fluctuations in the internal state, complicating analytical approaches. Previous studies focused on what happens when the negative feedback dominates the dynamics. By contrast, we show here that there is a large portion of physiologically-relevant parameter space where the positive feedback can dominate, even when gradients are relatively shallow. We demonstrate how large transients emerge because of non-normal dynamics (non-orthogonal eigenvectors near a stable fixed point) inherent in the positive feedback, and further identify a fundamental nonlinearity that strongly amplifies their effect. Most importantly, this amplification is asymmetric, elongating runs in favorable directions and abbreviating others. The result is a "ratchet-like" gradient climbing behavior with drift speeds that can approach half the maximum run speed of the organism. Our results thus show that the classical drawback of run-and-tumble navigation-wasteful runs in the wrong direction-can be mitigated by exploiting the non-normal dynamics implicit in the run-and-tumble strategy.


Simultaneous determination of nitrite and nitrate ions by air-segmented amplitude-modulated multiplexed flow analysis.
The concept of amplitude-modulated multiplexed flow analysis has been extended to the simultaneous determination of multiple analytes in a sample. A sample solution containing nitrite and nitrate ions is delivered from two channels, but the flow rates are varied at different frequencies. One of the channels has a reduction column for converting nitrate ions to nitrite ions. Downstream, the absorbance of the diazo-coupling product is monitored after the merging of both solutions with a Griess reagent. The signal is analyzed by a fast Fourier transform (FFT) in real time. From the thus-obtained amplitude, a µmol dm(-3) level of the ions can be determined. The introduction of air bubbles is effective to reduce any axial dispersion, and hence to improve the sensitivity.


Cephalexin in the treatment of upper respiratory tract infections.
Cephalexin, a semisynthetic cephalosporin antibiotic, has wide clinical application in respiratory infections of children and adults. In pharyngitis and tonsillitis due to beta-haemolytic streptococci, it is comparable to penicillin, cyclocillin, and cephaloglycin, as measured by clinical response, bacteriological cure rate, and incidence of relapse and reinfection. In otitis media, it is effective at dosages of 50-100 mg/kg/day except in those infections caused by Haemophilus influenzae, in which there is failure in 50% of the cases. In other infections of the upper respiratory tract, it appears to be effective except, again, in those caused by H. influenzae. Dosages of 1-2 g/day have been used in adults and 20-100 mg/kg/day in children. Adverse effects, mostly gastrointestinal upsets, rash, and urticaria, have been relatively infrequent and have not required discontinuance of the drug.


Elemental and cooperative diffusion in a liquid, supercooled liquid and glass resolved.
The diffusion mechanisms controlling viscous flow, structural relaxation, liquid-liquid phase separation, crystal nucleation, and crystal growth in multicomponent glass-forming liquids are of great interest and relevance in physics, chemistry, materials, and glass science. However, the diffusing entities that control each of these important dynamic processes are still unknown. The main objective of this work is to shed some light on this mystery, advancing the knowledge on this phenomenon. For that matter, we measured the crystal growth rates, the viscosity, and lead diffusivities in PbSiO3 liquid and glass in a wide temperature range. We compared our measured values with published data covering 16 orders of magnitude. We suggest that above a certain temperature range Td (1.2Tg-1.3Tg), crystal growth and viscous flow are controlled by the diffusion of silicon and lead. Below this temperature, crystal growth and viscous flow are more sluggish than the diffusion of silicon and lead. Therefore, Td marks the temperature where decoupling between the (measured) cationic diffusivity and the effective diffusivities calculated from viscosity and crystal growth rates occurs. We reasonably propose that the nature or size of the diffusional entities controlling viscous flow and crystal growth below Td is quite different; the slowest is the one controlling viscous flow, but both processes require cooperative movements of some larger structural units rather than jumps of only one or a few isolated atoms.


Psychodynamic Therapy: As Efficacious as Other Empirically Supported Treatments? A Meta-Analysis Testing Equivalence of Outcomes.
Pharmacotherapy, cognitive-behavioral therapy (CBT), and psychodynamic therapy are most frequently applied to treat mental disorders. However, whether psychodynamic therapy is as efficacious as other empirically supported treatments is not yet clear. Thus, for the first time the equivalence of psychodynamic therapy to treatments established in efficacy was formally tested. The authors controlled for researcher allegiance effects by including representatives of psychodynamic therapy and CBT, the main rival psychotherapeutic treatments (adversarial collaboration). The authors applied the formal criteria for testing equivalence, implying a particularly strict test: a priori defining a margin compatible with equivalence (g=0.25), using the two one-sided test procedure, and ensuring the efficacy of the comparator. Independent raters assessed effect sizes, study quality, and allegiance. A systematic literature search used the following criteria: randomized controlled trial of manual-guided psychodynamic therapy in adults, testing psychodynamic therapy against a treatment with efficacy established for the disorder under study, and applying reliable and valid outcome measures. The primary outcome was "target symptoms" (e.g., depressive symptoms in depressive disorders). Twenty-three randomized controlled trials with 2,751 patients were included. The mean study quality was good as demonstrated by reliable rating methods. Statistical analyses showed equivalence of psychodynamic therapy to comparison conditions for target symptoms at posttreatment (g=-0.153, 90% equivalence CI=-0.227 to -0.079) and at follow-up (g=-0.049, 90% equivalence CI=-0.137 to -0.038) because both CIs were included in the equivalence interval (-0.25 to 0.25). Results suggest equivalence of psychodynamic therapy to treatments established in efficacy. Further research should examine who benefits most from which treatment.


Investigation of oxidative stress in patients with alopecia areata and its relationship with disease severity, duration, recurrence and pattern.
Alopecia areata (AA) is an inflammatory autoimmune disease that causes hair loss on the scalp or trunk without scarring. Although the precise aetiopathogenesis of alopecia areata remains unknown, oxidative stress is thought to play a role. To investigate the relationship between severity and the role of oxidative stress in AA, by measuring plasma oxidant levels and antioxidant enzyme activities in erythrocytes. In total, 62 patients with AA (24 males and 38 females), and 62 sex- and age-matched healthy controls (HCs) were enrolled in the study. We investigated the levels of plasma malondialdehyde (MDA) and the activities of erythrocyte catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The relationship between oxidative stress and AA was also investigated with regard to disease pattern, severity, duration and recurrence. The mean erythrocyte GSH-Px and SOD activities were significantly reduced (P < 0.001 and P < 0.001 respectively) compared with the control group. Plasma MDA levels were increased but statistically insignificant (P = 0.08) in patients with AA compared with controls. No significant difference between erythrocyte CAT activities was observed between patients and controls (P = 0.2). In addition, we observed no statistically significant difference in patient plasma MDA levels or erythrocyte CAT, GSH-Px or SOD activities with regard to AA severity, duration, recurrence or pattern (P > 0.05). Patients with AA displayed reduced erythrocyte SOD and GSH-Px activities and enhanced plasma MDA levels. These findings support the possible role of oxidative stress in the pathogenesis of AA.


Monoclonal antibodies to 52-kilodalton protein of Salmonella typhi.
Ten monoclonal antibodies (6 immunoglobulin G1 kappa [IgG1 kappa] and 4 IgG2b kappa) from six hybrid clones specific for Salmonella typhi antigen were produced by immunizing BALB/cJ mice with affinity-purified S. typhi proteins (Bp). The latter were prepared by passing crude S. typhi Bp through an affinity column made from Sepharose conjugated to IgG antibodies against partially purified S. typhi Bp. The eluent was subsequently used as the immunogen for the production of monoclonal antibody. All 10 monoclonal antibodies reacted specifically with a 52-kilodalton (kDa) protein of S. typhi and were species specific. The presence of IgM antibody to the 52-kDa antigen in the sera of a majority of patients with acute typhoid fever suggested that this 52-kDa protein is also a good immunogen for humans. The potential usefulness of this antigen in the early diagnosis of typhoid fever is discussed.


A functional model for classifying metastatic lesions integrating scans and biomarkers.
Perfusion computed tomography is an emerging functional imaging modality that uses physiological models to quantify characteristics pertaining to the passage of fluid through blood vessels. Perfusion characteristics provide physiological correlates for neovascularization induced by tumor angiogenesis and thus a quantitative basis for cancer detection, prognostication, and treatment monitoring. We consider a liver cancer study where patients underwent a dynamic computed tomography protocol to enable evaluation of multiple perfusion characteristics derived from interrogating the time-attenuation of the concentration of the intravenously administered contrast medium. The objective is to determine the effectiveness of using perfusion characteristics to identify and discriminate between regions of liver that contain malignant tissues from normal tissue. Each patient contributes multiple regions of interest which are spatially correlated due to the shared vasculature. We propose a multivariate functional data model to disclose the correlation over time and space as well as the correlation among multiple perfusion characteristics. We further propose a simultaneous classification approach that utilizes all the correlation information to predict class assignments for collections of regions. The proposed method outperforms conventional classification approaches in the presence of strong spatial correlation. The method offers maximal relative improvement in the presence of temporal sparsity wherein measurements are obtainable at only a few time points.


[Transvaginal echography. An application in the diagnosis of cervical incompetence].
It has already been demonstrated that abdominal ultrasound is an adequate method for measuring the cervix in pregnancy. The use of the vaginal route for such measurement is new. We have been using for the vaginal approach an ultrasound transducer of 5 mHZ with an angle of sweep of 240 degrees. The study was carried out on 23 pregnant women at the 28th week of pregnancy who had been admitted because of threatened premature labour with possible cervical incompetence; and on 20 cases of normal pregnancy also at the 28th week, which is the time when we do glucose estimations normally in our antenatal clinics. The result of our work shows that this ultrasonic method through the vagina gives us much more accurate measurements of the cervix than digital vaginal examination does. A mean difference of 12.3 mm in the length of the cervix was found in normal pregnancies (46.3 mm) and in cases where there was a question of cervical incompetence (34 mm). Furthermore the phenomena of shortening, dilatation of the cervix and a funnel-shape of the internal os are ultrasound signs of value in diagnosing incompetent cervix. Further advantages of the transvaginal approach are that there is no need for the bladder to be filled previously, and that the organs are nearer which improves the ultrasound picture. All the same, it is to be emphasized that transvaginal ultrasound can only be a factor to be added to clinical examination in the diagnosis of the incompetent cervix.


Effect of compressional force on tablets containing cellulosic disintegrators I: Dimensionless disintegration values.
Spray-dried lactose tablets containing cellulosic disintegrators or microcrystalline cellulose were compressed at different compressional forces. USP disintegration times were measured as a function of pH and compressional force. Two dimensionless quantities were derived from the experimentally determined disintegration times, and their utility in the study of tablet formulations was demonstrated. These dimensionless quantities were used to assess the effect of compressional force and pH on disintegration behavior as well as to compare disintegrator efficiency. Two internally cross-linked sodium carboxymethylcellulose disintegrators were found to be the most efficient; their efficiency increased with increasing compressional force at all pH values.


[Ductoplasty of the post-traumatic stricture of a parotid duct].
A report on the primary application of the modern technique of plastic removal of stricture of the Stenonic duct. A clinical case of surgical intervention in the localization of stricture and salivary stone is considered. The analysis of the patient's medical history, ultrasound diagnostics, multispiral computed tomography of the maxillofacial region was carried out. Based on the results of the examination, the choice of the surgical intervention technique was made.


Characteristics and Long-Term Outcome of 535 Patients with Autoimmune Hepatitis-The 20-Year Experience of a High-Volume Tertiary Center.
Background and aims: Autoimmune hepatitis (AIH) is a complex and progressive inflammatory liver disease characterized by immune-mediated destruction of the liver parenchyma, hypergammaglobulinemia, the presence of circulating autoantibodies, and good response to immunosuppressive therapy. Since the prevalence of AIH is relatively rare, data on the clinical course and the long-term outcome are scarce. Patients and methods: We retrospectively analyzed the data of 535 well-documented AIH patients treated at the University Hospital Essen between 2000 and 2020. Results: The majority of patients were middle-aged females (75% women, mean age 45 years) with AIH type 1 (97%). Approximately 32% of patients were diagnosed with cirrhosis due to AIH, 29% had concomitant autoimmune (predominantly autoimmune thyroiditis), and 10% had psychiatric diseases, respectively. Skin tumors were the most common malignant diseases (47% of all tumors), while hepatocellular carcinoma rarely occurred (only six cases). Overall long-term mortality and liver-associated mortality were 9.16% and 4.67%, respectively. However, long-term survival was strongly associated with disease remission. Conclusions: Although AIH is a silent disease and cirrhosis is present in many cases, a favorable long-term prognosis can be achieved by consequent immunosuppressive therapy. The incidence of (liver-associated) complications seems to be lower in comparison to other etiologies, such as viral hepatitis or NASH, and mainly depends on the long-term side effects of immunosuppressive therapy.


Antifungal immunity and adjuvant cytokine immune enhancement in cancer patients with invasive fungal infections.
Invasive fungal infections are common in severely immunosuppressed patients with cancer and in recipients of haematopoietic transplants. Response to antifungal therapy alone is often inadequate. Pro-inflammatory cytokines are critical for promoting innate and adaptive cellular antifungal immune responses. Recombinant cytokines, including granulocyte-macrophage-colony stimulating factor and interferon-gamma, have been studied as adjuvant therapies for severely immunosuppressed cancer patients with difficult-to-treat invasive mycoses. The limited clinical experience to date shows a possible benefit of these cytokines, and further controlled clinical trials are needed to validate their routine use in cancer patients and stem-cell transplant recipients with invasive fungal infections who are likely to have a poor response to antifungal drug therapy.


Characterization of Diastereo- and Enantioselectivity in Degradation of Synthetic Pyrethroids in Soils.
Permethrin (PM), cypermethrin (CP), and cyfluthrin (CF) are three important synthetic pyrethroids, which contain two, four, and four enantiomeric pairs (diastereomers) and thus have four, eight, and eight stereoisomers, respectively. In this study, the stereo- and enantioselective degradation of PM, CP, and CF in a Shijiazhuang alkaline yellow soil and a Wuhan acidic red soil were studied in detail by a combination of achiral and chiral high-performance liquid chromatography (HPLC). The results showed that PM, CP, and CF degraded faster in Shijiazhuang soil than in Wuhan soil, and the dissipation rate followed an order of PM > CF > CP in both soils. The three pyrethroids exhibited similar diastereomer selectivity, while CP and CF showed higher enantioselectivity than PM. Moreover, the trans-diastereomers degraded faster, and showed higher enantioselectivity than the corresponding cis-diastereomers. For PM, the enantiomer 1S-trans-PM degraded most rapidly in both soils. As for CP and CF, the highest enantioselectivity was observed for diastereomer trans-3, and the insecticidally active enantiomer 1R-trans-αS degraded fastest among the 8 CP or CF stereoisomers in both soils. In addition, the Wuhan acidic soil displayed higher diastereomer and enantiomer selectivity than the Shijiazhuang alkaline soil for the three pyrethroids. Further incubation of CF in an alkaline-treated Wuhan soil showed that the dissipation rate greatly increased and the diastereo- and enantioselectivity significantly decreased after the alkaline treatment process.


A Somatic Coliphage Threshold Approach To Improve the Management of Activated Sludge Wastewater Treatment Plant Effluents in Resource-Limited Regions.
Effective wastewater management is crucial to ensure the safety of water reuse projects and effluent discharge into surface waters. Multiple studies have demonstrated that municipal wastewater treatment with conventional activated sludge processes is inefficient for the removal of a wide spectrum of viruses in sewage. In this study, a well-accepted statistical approach was used to investigate the relationship between viral indicators and human enteric viruses during wastewater treatment in a resource-limited region. Influent and effluent samples from five urban wastewater treatment plants (WWTPs) in Costa Rica were analyzed for somatic coliphage and human enterovirus, hepatitis A virus, norovirus genotypes I and II, and rotavirus. All WWTPs provide primary treatment followed by conventional activated sludge treatment prior to discharge into surface waters that are indirectly used for agricultural irrigation. The results revealed a statistically significant relationship between the detection of at least one of the five human enteric viruses and somatic coliphage. Multiple logistic regression and receiver operating characteristic curve analysis identified a threshold of 3.0 × 103 (3.5 log10) somatic coliphage PFU per 100 ml, which corresponded to an increased likelihood of encountering enteric viruses above the limit of detection (>1.83 × 102 virus targets/100 ml). Additionally, quantitative microbial risk assessment was executed for farmers indirectly reusing WWTP effluent that met the proposed threshold. The resulting estimated median cumulative annual disease burden complied with World Health Organization recommendations. Future studies are needed to validate the proposed threshold for use in Costa Rica and other regions.IMPORTANCE Effective wastewater management is crucial to ensure safe direct and indirect water reuse; nevertheless, few countries have adopted the virus log reduction value management approach established by the World Health Organization. In this study, we investigated an alternative and/or complementary approach to the virus log reduction value framework for the indirect reuse of activated sludge-treated wastewater effluent. Specifically, we employed a well-accepted statistical approach to identify a statistically sound somatic coliphage threshold value which corresponded to an increased likelihood of human enteric virus detection. This study demonstrates an alternative approach to the virus log reduction value framework which can be applied to improve wastewater reuse practices and effluent management.


Ascorbate depletion as a consequence of product recycling during dopamine beta-monooxygenase catalyzed selenoxidation.
The competence of dopamine beta-monooxygenase (DBM) to process selenide substrates was investigated, in anticipation that the expected selenoxide products would exhibit unique reactivity and redox properties. The prototypical selenide phenyl 2-aminoethyl selenide (PAESe) was synthesized and shown to be a substrate for DBM with the characteristic e/O2 ratio of 2:1 for monooxygenation. The kinetic parameters for oxygenation of PAESe were found to be similar to those for the DBM-catalyzed sulfoxidation of the cognate sulfide phenyl 2-aminoethyl sulfide [May, S. W., & Phillips, R. S. (1980) J. Am. Chem. Soc. 102, 5981-5983], and selenoxidation was stimulated by fumarate in a manner similar to other well-characterized DBM monooxygenation reactions. Identification of phenyl 2-aminoethyl selenoxide (PAESeO) as the enzymatic product was accomplished by the demonstration of coincident elution of authentic PAESeO with the enzymatic product in three significantly different HPLC systems. PAESeO was found to oxidize ascorbic acid with the concomitant and stoichiometric reduction of PAESeO back to the selenide, PAESe. As a consequence of this nonenzymatic reaction, ascorbate-supported DBM turnover was prematurely terminated under standard assay conditions due to depletion of reduced ascorbate. The kinetics of the redox reaction between PAESeO and ascorbate were investigated with a spectrophotometric assay of ascorbate at 300 nm, and a second-order rate constant of 3.4 M-1 s-1 was determined at pH 5.0, 25 degrees C. Spectrophotometric assay of cytochrome c (cyt c) reduction at 550 nm during the oxidation of ascorbate by PAESeO demonstrated that no cyt c trappable semidehydroascorbate was produced in this nonenzymatic reaction.(ABSTRACT TRUNCATED AT 250 WORDS)


Designing for Temporal Awareness: The Role of Temporality in Time-Critical Medical Teamwork.
This paper describes the role of temporal information in emergency medical teamwork and how time-based features can be designed to support the temporal awareness of clinicians in this fast-paced and dynamic environment. Engagement in iterative design activities with clinicians over the course of two years revealed a strong need for time-based features and mechanisms, including timestamps for tasks based on absolute time and automatic stopclocks measuring time by counting up since task performance. We describe in detail the aspects of temporal awareness central to clinicians' awareness needs and then provide examples of how we addressed these needs through the design of a shared information display. As an outcome of this process, we define four types of time representation techniques to facilitate the design of time-based features: (1) timestamps based on absolute time, (2) timestamps relative to the process start time, (3) time since task performance, and (4) time until the next required task.


Icariin promotes expression of PGC-1alpha, PPARalpha, and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro.
To investigate the effect of icariin on the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha), peroxisome proliferator-activated receptor alpha (PPARalpha), and nuclear respiratory factor 1 (NRF-1) on cardiomyocyte differentiation of murine embryonic stem (ES) cells in vitro. The cardiomyocytes derived from murine ES cells were verified by immunocytochemistry using confocal laser scanning microscopy. Cardiac-specific sarcomeric proteins (ie alpha-actinin, troponin T) were evaluated when embryoid bodies (EB) were treated with icariin or retinoid acid. The expression of PGC-1alpha, PPARalpha, and NRF-1 were analyzed using both semiquantitative RT-PCR and Western blotting in cardiomyocyte differentiation. The phosphorylation of the p38 mitogen-activated protein kinase (MAPK) was studied in the differentiation process, and its specific inhibitor SB203580 was employed to confirm the function of the p38 MAPK on icariin-induced cardiac differentiation. The application of icariin significantly induced the cardiomyocyte differentiation of EB as indicated by the promoted expression of alpha-actinin and troponin T. The expression of PGC-1alpha, PPARalpha, and NRF-1 increased coincidently in early differentiation and the increase was dose-dependently upregulated by icariin treatment. The phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8, and the activation was further enhanced and prolonged when the EB were subjected to icariin, which was concurrent with the elevation of PGC-1alpha, PPARalpha, and NRF-1. Moreover, the inhibition of the p38 MAPK pathway by SB203580 efficiently abolished icariin-stimulated cardiomyocyte differentiation and resulted in the capture of the upregulation of PGC-1alpha, PPARalpha, and NRF-1. Taken together, icariin promoted the expression of PGC-1alpha, PPARalpha, and NRF-1 during cardiomyocyte differentiation of murine ES cells in vitro and the effect was partly responsible for the activation of the p38 MAPK.


[Palliative gastroenteroanastomosis in pancreatic carcinoma].
The surgical treatment of pancreatic carcinoma is palliative in 90% of cases. The authors report their experience with 25 patients with unresectable pancreatic exocrine cancer, 23 of whom underwent palliative surgery. Sixteen patients had a bilioenteric by-pass and in 7 cases a gastroenterostomy was associated. The postoperative mortality rate was 8.7% and morbidity 28.6%. Eight patients with bilioenteric bypass only survived and only two of these required gastroenterostomy later on because of neoplastic duodenal obstruction. The shorter hospital stay and the longer survival of patients treated by bilioenteric by-pass only suggest that prophylactic gastroenterostomy is unnecessary and should be associated in selected patients only.


SUMO, Ubiquitin, UBL Proteins: Implications For Human Diseases - Fifth International Conference.
The fifth international conference on SUMO, Ubiquitin, UBL Proteins: Implications for Human Diseases, held in Houston, included topics covering the latest advances and new targets in the field of protein modification. This conference report highlights selected presentations on the structural characterization of ubiquitination and SUMOylation machinery; the regulation of ubiquitination enzymes, including E3 ligases; the functions and mechanism of action of SUMO-targeted ubiquitin ligases (STUbLs); the regulation of gene expression by SUMO; non-degradative functions of ubiquitin and SUMO in signal transduction; mechanisms and functions of ISG15 conjugation; the interaction of pathogens with host cell SUMOylation machinery; and stabilization of the Axin protein. Investigational drugs discussed include MLN-4924 (Millennium Pharmaceuticals Inc).


Weakening interaction suppresses spontaneous symmetry breaking in two-channel asymmetric exclusion processes.
This paper has studied spontaneous symmetry breaking (SSB) phenomenon in two types of two-channel asymmetric simple exclusion processes (ASEPs). One common feature of the two systems is that interactions for each species of particle happen at only one site, and the system reduces to two independent ASEPs when interaction vanishes. It is shown that with the weakening of interaction, the SSB is suppressed. More interestingly, the SSB disappears before the interaction is eliminated. Our work thus indicates that local interaction has to be strong enough to produce SSB. The mean-field analysis has been carried out, and the results are consistent with the simulation ones.


Designing an App for Immunosuppression Adherence and Communication: A Qualitative Approach.
Immunosuppression nonadherence may be the most important factor limiting long-term allograft survival. Following user-centered design, we explored the essential priorities and preferences of kidney transplant recipients and healthcare providers (HCP) to inform development of a smartphone app to improve immunosuppression adherence and communication. A qualitative descriptive research design was used. The University of Alberta Hospital adult kidney transplant program in Edmonton, Canada. Participants were recruited by convenience sampling and included 32 kidney transplant recipients and 11 HCPs. Seven focus groups (5 with recipients and 2 with HCPs) were conducted to inform app development. Sessions were recorded, and transcripts were coded to elucidate themes. App development to improve adherence was not a priority for HCP. Recipients prioritized choice: that all features be optional. Recipients preferred support while traveling; access to laboratory results; and use by younger or newly transplanted recipients. Both recipients and HCP preferred linkage to pharmacy; and self-management and accountability.For the app to improve communication, HCPs believed the priorities to be addressed included: clarity on scope of app; legal, ethical, and professional obligations; and charting. Both recipients and HCP prioritized HCP workload, and broader medication and health concerns. Healthcare providers preferred tech support; both recipients and HCPs preferred app access for nontransplant HCP. Limitations include underrepresentation of physicians, recipients with racial/ethnic diversity, and potential selection bias of transplant recipients who perceived themselves to be adhering to immunosuppression medications. Future research is needed for the app to become a comprehensive, secure platform for broader communication between recipients and HCP, pharmacies, and nontransplant clinicians while streamlining HCP workload.


Management of life-threatening airway obstruction caused by benign thyroid disease.
Goitre presenting with acute, life-threatening airway compromise is an uncommon indication for thyroid surgery. The management of this critical condition is controversial. To investigate the incidence of life-threatening airway compromise in patients with benign goitre, to investigate the predisposing factors, and to outline an optimal management policy for such critical cases. Retrospective review of the medical records of patients presenting with life-threatening, acute airway compromise secondary to benign thyroid disease, treated by the senior author (CT) between July 1994 and July 2005. Of a total of 505 thyroid surgery procedures over the 11-year period, five patients with benign thyroid disease had presented with life-threatening, acute airway compromise. Three of the five patients had been thyrotoxic and two of these had received an iodine load prior to airway compromise. Immediate endotracheal intubation for airway control followed by admission to the intensive care unit had been the presentation in two patients. An incidental diagnosis of tracheal compression had been made from the computed tomography (CT) scan in two patients who had non-resolved obstructive airway disease. Emergency thyroidectomy had been performed in all five patients. Significant tracheomalacia had been noted in four patients. Following thyroidectomy, two patients had required tracheostomy and one had required tracheal stenting. Chronic obstructive airways disease, substernal extension and long-standing goitre are considered as risk factors for developing acute, life-threatening airway compromise in the presence of benign thyroid disease. A recent iodine load may lead to airway compromise in thyrotoxic patients. A CT scan is indicated in cases of unresponsive chronic obstructive airways disease to rule out substernal extension of non-palpable goitres. Life-threatening airway compromise secondary to benign goitres is best treated by endotracheal intubation if conservative measures fail, followed by emergency thyroidectomy. Following surgery, close observation is mandatory to exclude airway compromise due to tracheomalacia and laryngeal oedema.


Planetary Health Nursing.
Planetary health is focused on the interconnectedness of the health of humans, other species, and the physical environment. Disruption of the Earth's natural ecosystems due to human overconsumption; disregard for sustainable practices; and the domination of other humans, species, and natural systems has led to an urgent moment in which humans must act to preserve these ecosystems, which support life on this planet. Restoring planetary health requires new directions for nursing. The pragmatic implications for nursing research, education, advocacy, and practice are explored in this article.


Smile Alabama! Initiative: interim results from a program to increase children's access to dental care.
Alabama faced an oral health crisis, with decreasing dental provider participation and increasing enrollment of Medicaid-eligible children. In response, the Smile Alabama! initiative was designed to improve oral health care services for Medicaid-eligible children by increasing the number of participating dentists by 15% and the number of children receiving dental care annually by 5% by January 31, 2004. The initiative is composed of 4 specific components: claims processing, dental reimbursement, provider education and recruitment, and recipient education. Specific interventions were implemented for each component. From fiscal year 1999 to fiscal year 2002, enrollment of targeted Medicaid children increased 32.7%. During this same period, the number of participating dental providers in the Alabama Medicaid dental program increased by 127 providers, a 38.7% increase. The number of children receiving dental services increased from 82,600 in fiscal year 1999 to 130,208 in fiscal year 2002, a 57.1% total increase, with a 4.8% increase in the annual dental visit rate. The experience suggests that access to oral health care services can be improved through a multidimensional, strategically planned dental outreach initiative in spite of dramatic increases in Medicaid enrollment.


[Identification of peptides binding to Pisum sativum agglutinin from a phage-displayed random peptide library].
To obtain peptides binding specifically to Pisum sativum agglutinin (PSA) from a phage-displayed random peptide library. (1) A phage-displayed random hexapeptide library was screened with PSA as target. (2) Dot blot was used to analyze the influence of the alpha-Met-D-mannoside on binding between PSA and phage-displayed peptides. (3) Three peptides (RMWSF, RYDYSY, LRLRQL) were selectively synthesized, and different concentrations were used to inhibit PSA and ConA binding to the HRP. The enrichment occurred obviously after three rounds of screening. The insert sequences of amino acids, displayed on 22 phage DNAs from the third round of screening, were divided into three groups. The binding of phage-displayed peptides to PSA was specific as shown by dot blot and could be inhibited by alpha-Met-D-mannoside. LRLRQL was not dissolved in water. ARMWSF and RYDYSY inhibited binding of PSA to HRP, but failed to inhibit binding ConA to HRP. The binding site of peptides ARMWSF and RYDYSY is different to that of alpha-Met-D-mannoside.


'Very brief advice' (VBA) on smoking in family practice: a qualitative evaluation of the tobacco user's perspective.
Very Brief Advice on smoking (VBA) is an evidence-based intervention designed to increase quit attempts among patients who smoke. VBA has been widely disseminated in general practice settings in the United Kingdom, however its transferability to Southern European settings is not well established. This study sought to document the perspectives of Greek general practice patients in terms of the acceptability and satisfaction with receiving VBA from their general practitioner (GP) and its influence on patients' motivation to make a quit attempt. We also examine patient identified barriers and facilitators to acting on VBA. Semi-structured interviews were conducted with 50 patients who reported current tobacco use recruited from five general practices in Crete, Greece. All patients received VBA from their GP and interviews were conducted immediately after the GP appointment. Thematic analysis was used to analyze data. The majority of patients were satisfied with the VBA intervention. Approximately one quarter of patients reported they were motivated to make an attempt to quit smoking after receiving VBA from their GP. Patients identified a clear preference for VBA to be delivered in a supportive manner, which communicated genuine concern versus fear-based approaches. Patients with an existing smoking-related illness were more likely to report plans to act on their GP's VBA. Patients not ready to quit smoking indicated they would be likely to seek the support of their GP for future quit attempts as a result of VBA. Many patients reported low self-efficacy with quitting and apprehension about available quit smoking supports. VBA was positively received by the majority of smokers interviewed. Participating patients confirmed the motivational role of advice when delivered in a supportive and caring manner. Personal health status, beliefs about quit smoking supports, and low self-efficacy appear to influence patient's motivation to make an aided quit attempt.


[Management of comorbid diabetes and cancer in the elderly].
Diabetes mellitus is a frequent comorbidity of cancer patients especially in the elderly. Recent data show that diabetes may negatively impact both cancer risks and outcomes of treatment. It is important to identify patients at risk for complications that arise from cancer treatment in the setting of pre-existing diabetes. Additionally, underlying hyperglycemia or hidden diabetes in a patient undergoing cancer treatment such as chemotherapy including steroid administration and total parenteral nutrition should be identified and managed. Strategies for monitoring and managing hyperglycemia in the elderly during the course of cancer treatment will be reviewed. The role of interdisciplinary care is crucial to supporting patients and their families as they manage through the challenges of facing two life-threatening diseases.


Cosolute effects on the chemical potential and interactions of an IgG1 monoclonal antibody at high concentrations.
The solution thermodynamics and interactions of a reversibly self-associating IgG1 monoclonal antibody have been investigated as a function of cosolute type (NaCl, NaSCN, arginine-HCl) and cosolute concentration over a wide range of protein concentrations (1-235 mg/mL) using static light scattering. The nonideality of mAb solutions is analyzed within the simplifying framework of a two-component system to obtain the dependencies of the excess chemical potential of the mAb on protein and cosolute concentrations. Using hard spheres as a model of mAbs in the absence of intermolecular interactions, the mean interparticle distances can be estimated as a function of antibody concentration. Analysis of MAb1 excess chemical potential and mean intermolecular distance results in a potential function representing the sum of protein-protein interactions and their contributions to solution nonideality. This approach facilitates evaluation of the relative contributions of attractive/repulsive intermolecular interactions and excluded volume effects, as well as the effects of cosolutes on protein multiparticle interactions in crowded conditions. Underlying the dominant effect of volume exclusion at high protein concentrations, attractive interactions were found to be amplified with decreasing intermolecular distances by the MAb1 many-body correlations. Comparison of the cosolute concentration dependence of the protein chemical potential, dμ2(ex)/dC3, across the mAb concentrations demonstrates that MAb1 self-association is reduced with increasing ionic strength and in a series based on cosolute identity; Arg-Cl > NaSCN > NaCl. The effectiveness of arginine-HCl and NaSCN in modulating MAb1 excess chemical potential in concentrated solutions is ascribed to the cosolute's ability to mitigate both electrostatic as well as weaker hydrophobic attractive interactions between MAb1 molecules. This investigation presents the first direct analysis of cosolute specific effects on protein-protein interactions at high concentrations, and provides a novel approach for characterizing the many-body effects that contribute to solution nonideality.


Possible Roles of Periostin in the Formation of Hemodialysis Vascular Access Stenosis after Polytetrafluoroethylene Graft Implantation in Dogs.
Periostin, a recently found matricellular protein, has been implicated in neointima formation after balloon injury. However, the relationship between periostin and hyperplastic intima formation after PTFE graft implantation is unclear. Under mixed anesthesia, PTFE grafts were implanted between the canine carotid artery and jugular vein, and PTFE graft samples were harvested 1, 2, and 4 months after implantation. Intima formation started on the luminal surface of PTFE grafts at the venous anastomotic region 1 month after implantation. Thereafter, the increase in intimal volume was not only observed in the venous and arterial anastomotic regions, but also in the middle region of the PTFE grafts. In accordance with the increased intimal formation, time-dependent increases in mRNA expressions of periostin and transforming growth factor beta 1 (TGF-β1), as well as a strong positive correlation between periostin and TGF-β1, were observed. These findings suggest that periostin may play a very important role in the pathogenesis of hemodialysis vascular access stenosis through the acceleration of intimal formation. Thus, periostin may be a very important therapeutic target for the treatment of vascular access graft dysfunction in hemodialysis patients.


Disease phenocode analysis identifies SNP-guided microRNA maps (MirMaps) associated with human "master" disease genes.
Recently we reported the results of a genome-wide disease phenocode analysis interrogating the relationships between structural features and gene expression patterns of disease-linked SNPs, microRNAs and mRNAs of protein-coding genes in association to phenotypes of 15 common human disorders (Cell Cycle 2008;7:2570-83; 3564-76). One of the main implications of this analysis is that transcriptionally co-regulated SNP sequence-bearing RNAs are more likely to exert a cumulative effect in trans on phenotypes. In this work, we test the validity of a disease phenocode concept within a genomic context of distinct continuously spaced sets of disease-linked SNPs and mRNAs of relevant proteincoding genes. We report a sequence homology profiling of two sets of disease-linked SNPs which are located within continuous genomic regions associated with individual protein-coding genetic loci (NLRP1 and STAT4) and are likely to exhibit common profiles of transcriptional activity. Most of microRNAs (15 of 19; 79%) homologous to the NLPRP1-associated disease-linked SNPs have potential protein-coding mRNA targets among the principal components of the nuclear import pathway (NIP) and/or inflammasome pathways, including KPNA1, NLRP1 and NLRP3 genes. We demonstrate that estimates of cumulative targeting effects of microRNAs on mRNAs within distinct allelic contexts of disease-linked SNPs are in agreement with microarray analysis-defined gene expression phenotypes associated with human genotypes of Crohn's disease (CD) and rheumatoid arthritis (RA) populations. Microarray experiments and disease phenocode analysis identify ten-gene expression signatures which seem to reflect the activated status of disease-linked SNPs/microRNAs/mRNAs axis in peripheral blood mononuclear cells (PBMC) of 66% CD patients and 80% RA patients. Comparisons of ten-gene signature expression profiles and NLRP3/NLRP1 mRNA expression ratios in PBMC of individual CD and RA patients and control subjects indicate that measurements of these markers may be useful for diagnostic applications. Our findings demonstrate that NLPRP1- and STAT4-associated disease-linked SNPs have common sequence-defined features which are recapitulating the essential phenotype-affecting features of genome-wide disease-linked SNPs, suggesting that NLRP1 (NALP1) and STAT4 genetic loci may constitute "master" disease genes. We conclude that both genome-wide SNP variations and SNP polymorphisms associated with "master" disease genes may cause similar genetically-defined malfunctions of the NIP and inflammasome/innate immunity pathways which are likely to contribute to pathogenesis of multiple common human disorders.


Vortex solitons in moiré optical lattices.
We show that optical moiré lattices enable the existence of vortex solitons of different types in self-focusing Kerr media. We address the properties of such states both in lattices having commensurate and incommensurate geometries (i.e., constructed with Pythagorean and non-Pythagorean twist angles, respectively), in the different regimes that occur below and above the localization-delocalization transition. We find that the threshold power required for the formation of vortex solitons strongly depends on the twist angle and, also, that the families of solitons exhibit intervals where their power is a nearly linear function of the propagation constant and they exhibit a strong stability. Also, in the incommensurate phase above the localization-delocalization transition, we found stable embedded vortex solitons whose propagation constants belong to the linear spectral domain of the system.


Polymorphism of human mu class glutathione transferases.
A combined database mining approach was used to detect polymorphisms in the mu class glutathione-S-transferase (GST) genes. Although a large number of potential polymorphisms were detected in the five genes that comprise the Mu class GSTs using sequence alignment programs and by searching single nucleotide polymorphism databases, the majority were not validated or detected in three major ethnic populations (African, Southern Chinese and Australian European). Two new polymorphisms were detected and characterized in the GSTM3 gene. A rare pG147W substitution was detected only in the Southern Chinese subjects. A more common pV224I substitution was found in each of the ethnic groups studied, and significant differences in allele frequencies were observed between each group. These two polymorphisms can combine to form four distinct haplotypes (GSTM3A [p.G147;V224], GSTM3C [p.G147;I224], GSTM3D [p.W147;V224], GSTM3E [p.W147;I224]). The four isoforms were expressed in Escherichia coli and characterized enzymatically with several substrates including 1-chloro-2,4-dinitrobenzene (CDNB), cumene hydroperoxide and t-nonenal. GSTM3-3 containing the variant p.W147 residue tended to show diminished specific activity and catalytic efficiency with CDNB. In contrast, GSTM3-3 containing the variant p.I224 residue tended to show increased specific activity and catalytic efficiency with CDNB. Interactions between the different p.147 and p.224 residues were also observed, with the GSTM3C isoform exhibiting the greatest activity with each substrate, and GSTM3E the lowest. These functional polymorphisms may play a significant role in modulating the ability of GSTM3-3 to metabolize substrates such as the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea.


Facile synthesis of multimeric micelles.
Bringing it all together: Synthesis of a dimeric micelle (see scheme) is shown to produce specifically linked Janus-like micelles. The reaction conditions for dimeric micelle formation were optimized and the resulting micelles characterized. Trimeric, tetrameric, and multimeric micelles were also synthesized using the same technique.


Maternal nutritional status and related pregnancy outcomes following bariatric surgery: A systematic review.
Up to 80% of patients who undergo bariatric surgery are women of childbearing age. Coupled with improved fertility in women with obesity after bariatric surgery, pregnancy postbariatric surgery has become increasingly more common. Although numerous studies have evaluated associations of bariatric surgery with pregnancy outcomes, the effect of maternal nutritional status on maternal and perinatal outcomes is not well established. We used Medline and Embase databases and a manual search of references for articles published until June 2018 to conduct a systematic review on nutritional status after bariatric surgery and its association with maternal and perinatal outcomes. Of the 306 initially identified articles, 27 met the study inclusion criteria, comprising 2056 women with pregnancies after bariatric surgery. Deficiencies were reported in maternal concentrations of vitamins A, B1, B6, B12, C, D, K, iron, calcium, selenium, and phosphorous. The only adverse events documented for these deficiencies encountered during pregnancy were anemia (vitamin B12, iron), night blindness (vitamin A), and urinary tract infections (vitamin A, D). This systematic review suggests that various micronutrient deficiencies are common among pregnant postbariatric surgery patients. Nevertheless, despite the concern that these deficiencies could adversely affect pregnancy outcomes (e.g., lower neonatal birth weight), evidence of such is lacking. Further prospective studies are warranted to confirm our findings and better delineate the optimal supplementation regimen during pregnancy after bariatric surgery.


Sexual abuse and drinking and drug use: implications for prevention.
Based on a survey of adolescent females in grades seven through twelve in a suburban school system, the relationship between drinking, drug use, and sexual abuse is examined. Using a holistic approach to adolescent deviant behavior, connections between family, peer, psychosocial factors and drug use and delinquency are explored. Girls who report sexual molestation are more likely to have used a number of drugs, different from the prevalence profile of the larger sample. Significant correlations for younger girls between sexual molestation and delinquency are also reported. Implications for school based drug prevention programs are discussed.