Design, synthesis, crystal structure analysis, and insecticidal evaluation of phenylazoneonicotinoids.
On the basis of research of the proposed modes of action between neonicotinoids and insect nicotinic acetylcholine receptor (nAChR), a series of phenylazoneonicotinoids were designed and synthesized to further promote the π-π interaction between molecule and amino acid residues. The target compounds have been identified on the basis of satisfactory analytical and spectral ((1)H NMR, (13)C NMR, HRMS, and X-ray) data. The preliminary results revealed that tiny differences in substitutes resulted in different configurations and great bioactivity variations. Some compounds with electron-donating groups on positions 2 and 6 of the phenyl ring presented higher insecticidal activity than imidacloprid against cowpea aphids ( Aphis craccivora ). The impressive crystal structure of the excellent insecticidal activity compound 9q clearly proved that the functional electronegative pharmacophore was approximately vertical to the methyleneimidazolidine plane. The differences in the mode of interaction on nAChR of typical compounds 9h and 9q remain unclear.


In Re Baby Doe, 23 February 1987.
The Court rejected an appeal by the husband plaintiff that he was not responsible for support payments for a child born to his wife as a result of artificial insemination. It held that he had consented to the insemination through his knowledge of and assistance in his wife's efforts to conceive through artificial insemination and was thus the legal father of the child with legal responsibilities toward it.


[Correct understanding of the non-surgical management options in the treatment of intermittent exotropia in children].
Intermittent exotropia is the commonest type of strabismus, and surgery is the primary treatment. Follow-ups and other non-surgical management options can be used for patients who are younger, less cooperative, with well controlled exotropia, or unwilling to operate. However, there are many misconceptions regarding the treatment, especially the non-surgical treatment of intermittent exotropia in children, due to lack of thorough understanding about the natural course of intermittent exotropia, the timing for surgery, and the suitable candidates, effectiveness, and potential risks of different non-surgical options. This article provide an objective evaluation about the common non-surgical management options of intermittent exotropia based on the international research findings and clinical experience, in order to facilitate the correct understanding and rational use of the non-surgical treatment.


Demographic transition and population aging in Korea.
"This paper describes the process of population aging in conjunction with the demographic transition in [South Korea]. Korea has recently experienced rapid decreases of both mortality and fertility, which have brought about the rapid process of population aging. The speed of...population aging in Korea is projected as one of the fastest in the world. Population aging brings about changing patterns of family composition, especially new trends of living arrangements of the elderly. Since the process of population aging [began] in Korea, the proportion of [those] living alone and [of those] living with spouse only have significantly increased."


Lymphoedema of the upper limb: a rare complication of thyroid surgery?
A 40-year-old woman underwent an elective thyroidectomy for a non-toxic, multinodular goitre. In the early postoperative period, the patient developed a significant unilateral swelling of the right upper limb, which was subsequently confirmed to be lymphoedema. This was eventually treated successfully using liposuction and compression garment therapies. We report the case due to its rarity and present a possible explanation for such an unexpected complication based on known anatomical variations of lymphatic drainage of the upper limb.


Phylogeographic analysis and species distribution modelling of the wood frog Batrachyla leptopus (Batrachylidae) reveal interglacial diversification in south western Patagonia.
The evolutionary history of southern South American organisms has been strongly influenced by Pleistocene climate oscillations. Amphibians are good models to evaluate hypotheses about the influence of these climate cycles on population structure and diversification of the biota, because they are sensitive to environmental changes and have restricted dispersal capabilities. We test hypotheses regarding putative forest refugia and expansion events associated with past climatic changes in the wood frog Batrachyla leptopus distributed along ∼1,000 km of length including glaciated and non-glaciated areas in southwestern Patagonia. Using three mitochondrial regions (D-loop, cyt b, and coI) and two nuclear loci (pomc and crybA1), we conducted multilocus phylogeographic analyses and species distribution modelling to gain insights of the evolutionary history of this species. Intraspecific genealogy was explored with maximum likelihood, Bayesian, and phylogenetic network approaches. Diversification time was assessed using molecular clock models in a Bayesian framework, and demographic scenarios were evaluated using approximate Bayesian computation (ABC) and extended Bayesian skyline plot (EBSP). Species distribution models (SDM) were reconstructed using climatic and geographic data. Population structure and genealogical analyses support the existence of four lineages distributed north to south, with moderate to high phylogenetic support (Bootstrap > 70%; BPP > 0.92). The diversification time of B. leptopus' populations began at ∼0.107 mya. The divergence between A and B lineages would have occurred by the late Pleistocene, approximately 0.068 mya, and divergence between C and D lineages was approximately 0.065 mya. The ABC simulations indicate that lineages coalesced at two different time periods, suggesting the presence of at least two glacial refugia and a postglacial colonization route that may have generated two southern lineages (p = 0.93, type I error: <0.094, type II error: 0.134). EBSP, mismatch distribution and neutrality indexes suggest sudden population expansion at ∼0.02 mya for all lineages. SDM infers fragmented distributions of B. leptopus associated with Pleistocene glaciations. Although the present populations of B. leptopus are found in zones affected by the last glacial maximum (∼0.023 mya), our analyses recover an older history of interglacial diversification (0.107-0.019 mya). In addition, we hypothesize two glacial refugia and three interglacial colonization routes, one of which gave rise to two expanding lineages in the south.


[Applied anatomy of the medial superior genicular artery and the retrograde island flap].
Through anatomical dissection of fifty freshly amputated adult lower extremities, the origin, length, diameter and extent of perfusion of the superior genicular artery and its relation with the anterior tibial recurrent artery were investigated. Results revealed that the medial superior genicular artery originated primarily from the femoral artery (95.5%). It descends between the sartorius and majormedial muscles and then separates into branches that nourish the upper one-third of the lower leg and the medial skin of the knee, and then, by anastomosis, joins the anterior tibia recurrent artery on the level of the medial malleolus of the tibia. The formation rate of the anastomotic arch is 100% with the average outer diameter of 1.3 +/- 0.39 mm (x +/- s). Based on these observations, we conclude that the medial area of the knee is the best donor site of an island flap, which can be used to repair the medial superior one-third of the lower leg and the region around the knee.


Aligning Air Force Ground Surgical Team (GST) Training With the Deployment Experience.
The Air Force Ground Surgical Team (GST) Phase 1 course is a two-week pre-deployment training for the Air Force's conventional austere surgical care platform. Since the creation of the GST platform and associated training pipeline in 2017, course adjustments and improvements have relied on expert opinion and anecdote. To gain a more robust understanding of GST deployment clinical and operational activities, we conducted a survey of all surgeons who completed GST Phase 1 training from its inception in April 2017 to September 2020. 87 surgeons took the course from April 2017 to September 2020. 60 of those surgeons were still on active duty and were candidates to complete the survey sent from the Air Force Survey Office. 31 individuals responded and their identification was kept blinded. An IRB exemption was issued before study initiation. Of the 31 respondents, 9 took the GST Phase 1 course but never deployed, and were excluded. The remaining 22 surgeons deployed at some point from 2017 to 2020. Four surgeons reported providing no surgical care during their deployment. 68% of the surgeons deployed to an actual standalone GST platform, while the rest were retained at larger military treatment facilities (MTFs) or Role III facilities. The median number of surgeries performed was 2 for surgeons at standalone GSTs and 7 for those at larger MTFs/Role IIIs. A holding time of greater than 12 hours was reported for 15% of operative patients and 58% of nonoperative patients at standalone GSTs. 28% (n = 5) of surgeons reported taking care of patients in the Golden Hour of surgery, and 23% of teams reported a patient death. Two surgeons cared for a military working dog, and four surgeons cared for pediatric patients. 50% of surgeons had more than one patient present simultaneously for care. 50% of surgeons' resupply were in the greater than 30 days or never received category. The GST Phase 1 course has a unique role in preparing students to provide austere surgical care. This includes both preparing to function in the operational military environment as well as applying sound in-garrison trauma surgical care techniques to the austere, resource variable environment. The results of this survey suggest that a broadening of content-specific deployment-related topics, the formalization of documentation education, incorporating formal evidence-based nontechnical skills training, and identifying optimal GST context-specific behaviors will strengthen the effectiveness of the course in preparing students for deployment.


Fenofibrate reduces plasma cholesteryl ester transfer from HDL to VLDL and normalizes the atherogenic, dense LDL profile in combined hyperlipidemia.
The effect of fenofibrate on plasma cholesteryl ester transfer protein (CETP) activity in relation to the quantitative and qualitative features of apoB- and apoA-I-containing lipoprotein subspecies was investigated in nine patients presenting with combined hyperlipidemia. Fenofibrate (200 mg/d for 8 weeks) induced significant reductions in plasma cholesterol (-16%; P < .01), triglyceride (-44%; P < .007), VLDL cholesterol (-52%; P = .01), LDL cholesterol (-14%; P < .001), and apoB (-15%; P < .009) levels and increased HDL cholesterol (19%; P = .0001) and apoA-I (12%; P = .003) levels. An exogenous cholesteryl ester transfer (CET) assay revealed a marked decrease (-26%; P < .002) in total plasma CETP-dependent CET activity after fenofibrate treatment. Concomitant with the pronounced reduction in VLDL levels (37%; P < .005), the rate of CET from HDL to VLDL was significantly reduced by 38% (P = .0001), whereas no modification in the rate of cholesteryl ester exchange between HDL and LDL occurred after fenofibrate therapy. Combined hyperlipidemia is characterized by an asymmetrical LDL profile in which small, dense LDL subspecies (LDL-4 and LDL-5, d = 1.039 to 1.063 g/mL) predominate. Fenofibrate quantitatively normalized the atherogenic LDL profile by reducing levels of dense LDL subspecies (-21%) and by inducing an elevation (26%; P < .05) in LDL subspecies of intermediate density (LDL-3, d = 1.029 to 1.039 g/mL), which possess optimal binding affinity for the cellular LDL receptor. However, no marked qualitative modifications in the chemical composition or size of LDL particles were observed after drug treatment. Interestingly, the HDL cholesterol concentration was increased by fenofibrate therapy, whereas no significant change was detected in total plasma HDL mass. In contrast, the HDL subspecies pattern was modified as the result of an increase in the total mass (11.7%) of HDL2a, HDL3a, and HDL3b (d = 1.091 to 1.156 g/mL) at the expense of reductions in the total mass (-23%) of HDL2b (d = 1.063 to 1.091 g/mL) and HDL3c (d = 1.156 to 1.179 g/mL). Such changes are consistent with a drug-induced reduction in CETP activity. In conclusion, the overall mechanism involved in the fenofibrate-induced modulation of the atherogenic dense LDL profile in combined hyperlipidemia primarily involves reduction in CET from HDL to VLDL together with normalization of the intravascular transformation of VLDL precursors to receptor-active LDLs of intermediate density.


Haemorrhage requiring embolisation after low energy pelvic fracture in an elderly patient: a case report.
An 89-year-old woman presented with a stable fracture of the pelvis following a low energy trauma. The patient was taking no anticoagulation medication and was found to have life-threatening pelvic bleeding which required embolisation. Stable pelvic fractures following low energy trauma are common injuries in the elderly and frequently require admission for pain relief and mobility management. This case highlights that severe pelvic bleeding is a possible, life-threatening sequela after low energy pelvic injury in the elderly, and careful attention must be paid to the signs of active haemorrhage.


Heritable and life-style determinants of bone mineral density.
Familial resemblance in bone mineral density at five skeletal sites was measured among 160 adult members of 40 families. Each family included a postmenopausal mother, one premenopausal daughter, one son, and the children's father. Similarities in selected life-style factors thought to influence bone density, such as physical activity, smoking, alcohol use, and diet, were also evaluated. Bone density was measured by dual-energy (total body, femoral neck, and lumbar spine) or single-photon (radius and os calcis) absorptiometry. Correlation coefficients between the midparent Z score and offspring Z scores of bone mineral density ranged from 0.22 to 0.52 among daughters and from 0.27 to 0.58 among sons. Adjustment of bone density for age, height, weight, and significant life-style or environmental factors yielded heritability estimates for the five skeletal sites between 0.46 and 0.62. That is, 46-62% of variance in bone density was attributable to heredity. Most estimates derived from the group of daughters were similar to those from the sons. These observations provide support for a significant contribution of heredity to bone density. However, an individual's life-style may account for a potentially large proportion of the nonheritable variance in bone density.


Subclassification of presynaptic alpha 2-adrenoceptors: alpha 2D-autoreceptors in guinea-pig atria and brain.
The study was devised to classify, by means of antagonist and agonist affinities, the presynaptic alpha 2-autoreceptors in guinea-pig heart atria and brain cortex in terms of alpha 2A, alpha 2B, alpha 2C and alpha 2D. A set of antagonists and agonists was chosen that was able to discriminate between the four subtypes. Small pieces of the atria and slices of the brain cortex were preincubated with 3H-noradrenaline and then superfused and stimulated electrically. In one series of experiments (atria only), tissue pieces were stimulated by relatively long pulse trains (1 min) leading to marked alpha 2-autoinhibition. All 10 antagonists increased the evoked overflow of tritium. pEC30% values (concentrations causing 30% increase) were interpolated from concentration-response curves. In a second series of experiments (atria and brain slices), tissue pieces were stimulated by brief pulse trains (0.4 s or 40 ms) that led to little (atria) or no (brain slices) alpha 2-autoinhibition, and antagonist effects against the alpha 2-selective agonist 5-bromo-6-(2-imidazolin-2- ylamino)-quinoxaline (UK 14,304) were examined. All 10 (atria) or 8 (brain) antagonists shifted the concentration-inhibition curve of UK 14,304 to the right. pKd values of the antagonists were calculated from the shifts. In a third series of experiments (brain slices only), also with brief pulse trains (40 ms), pKa values (negative logarithms of dissociation constants of agonist-alpha 2-adrenoceptor complexes) were determined by comparison of concentration-inhibition curves of UK 14,304, guanoxabenz and oxymetazoline in normal tissue and in tissue in which a fraction of the receptors had been blocked by phenoxybenzamine.(ABSTRACT TRUNCATED AT 250 WORDS)


What influences literacy outcome in children with speech sound disorder?
In this study, the authors evaluated literacy outcome in children with histories of speech sound disorder (SSD) who were characterized along 2 dimensions: broader language function and persistence of SSD. In previous studies, authors have demonstrated that each dimension relates to literacy but have not disentangled their effects. Methods Two groups of children (86 SSD and 37 controls) were recruited at ages 5-6 and were followed longitudinally. The authors report the literacy of children with SSD at ages 7-9, compared with controls and national norms, and relative to language skill and SSD persistence (both measured at age 5-6). The SSD group demonstrated elevated rates of reading disability. Language skill but not SSD persistence predicted later literacy. However, SSD persistence was associated with phonological awareness impairments. Phonological awareness alone predicted literacy outcome less well than a model that also included syntax and nonverbal IQ. Results support previous literature findings that SSD history predicts literacy difficulties and that the association is strongest for SSD + language impairment (LI). Magnitude of phonological impairment alone did not determine literacy outcome, as predicted by the core phonological deficit hypothesis. Instead, consistent with a multiple deficit approach, phonological deficits appeared to interact with other cognitive factors in literacy development.


Stent-assisted coil embolization of a mycotic renal artery aneurysm by use of a self-expanding neurointerventional stent.
Mycotic aneurysms are uncommon, especially those located in visceral arteries. We present a case of a patient with two visceral mycotic aneurysms due to bacterial endocarditis, one located in right upper pole renal artery and the second in the splenic artery. Both aneurysms were treated as endovascular embolization using microcoils. In the aneurysm located at the renal artery, the technique of stent-assisted coils embolization was preferred to avoid coils migration due to its wide neck. The stent used was the Solitaire AB, which was designed for the treatment of intracranial aneurysms and was used recently in acute stroke as a mechanical thrombectomy device. Complete embolization of the aneurysm was achieved, preserving all the arterial branches without nephrogram defects in the final angiogram.


Testing decision rules for categorizing species' extinction risk to help develop quantitative listing criteria for the U.S. Endangered Species Act.
Lack of guidance for interpreting the definitions of endangered and threatened in the U.S. Endangered Species Act (ESA) has resulted in case-by-case decision making leaving the process vulnerable to being considered arbitrary or capricious. Adopting quantitative decision rules would remedy this but requires the agency to specify the relative urgency concerning extinction events over time, cutoff risk values corresponding to different levels of protection, and the importance given to different types of listing errors. We tested the performance of 3 sets of decision rules that use alternative functions for weighting the relative urgency of future extinction events: a threshold rule set, which uses a decision rule of x% probability of extinction over y years; a concave rule set, where the relative importance of future extinction events declines exponentially over time; and a shoulder rule set that uses a sigmoid shape function, where relative importance declines slowly at first and then more rapidly. We obtained decision cutoffs by interviewing several biologists and then emulated the listing process with simulations that covered a range of extinction risks typical of ESA listing decisions. We evaluated performance of the decision rules under different data quantities and qualities on the basis of the relative importance of misclassification errors. Although there was little difference between the performance of alternative decision rules for correct listings, the distribution of misclassifications differed depending on the function used. Misclassifications for the threshold and concave listing criteria resulted in more overprotection errors, particularly as uncertainty increased, whereas errors for the shoulder listing criteria were more symmetrical. We developed and tested the framework for quantitative decision rules for listing species under the U.S. ESA. If policy values can be agreed on, use of this framework would improve the implementation of the ESA by increasing transparency and consistency.


Mechanoresponsive musculoskeletal tissue differentiation of adipose-derived stem cells.
Musculoskeletal tissues are constantly under mechanical strains within their microenvironment. Yet, little is understood about the effect of in vivo mechanical milieu strains on cell development and function. Thus, this review article outlines the in vivo mechanical environment of bone, muscle, cartilage, tendon, and ligaments, and tabulates the mechanical strain and stress in these tissues during physiological condition, vigorous, and moderate activities. This review article further discusses the principles of mechanical loading platforms to create physiologically relevant mechanical milieu in vitro for musculoskeletal tissue regeneration. A special emphasis is placed on adipose-derived stem cells (ADSCs) as an emerging valuable tool for regenerative musculoskeletal tissue engineering, as they are easily isolated, expanded, and able to differentiate into any musculoskeletal tissue. Finally, it highlights the current state-of-the art in ADSCs-guided musculoskeletal tissue regeneration under mechanical loading.


Proline dehydrogenase: a key enzyme in controlling cellular homeostasis.
Proline dehydrogenase (ProDH), also called proline oxidase (POX), is a universal enzyme in living organisms. It catalyzes the oxidation of L-proline to delta1-pyrroline-5-carboxylate leading to the release of electrons, which can be transferred to either electron transfer systems or to molecular oxygen. ProDH is not only essential for proline catabolism but also plays key roles in providing energy, shuttling redox potential between cellular compartments and reactive oxygen species production. Structural analysis of prokaryotic ProDHs already gives some insights into the biochemical activity and biological functions of this enzyme, which can be extended to eukaryotic ProDHs based on sequence similarities. Here we report the most recent investigations on the biochemical and regulation of ProDH at transcriptional, post-transcriptional and translational levels. The biological roles of ProDH in cell homeostasis and adaptation through energetic, developmental, adaptive, physiological and pathological processes in eukaryotes are presented and discussed to create a framework for future research direction.


Developing a multisite project in geriatric and/or gerontological education with emphases in interdisciplinary practice and cultural competence.
This 2-year, multisite, curriculum-development project aimed to increase the pool of professionals trained in geriatric and/or gerontological social work. Our methods included (a) providing advanced training in aging, cultural competence, and interdisciplinary practice to social work professionals and masters degree students, (b) developing, implementing, and testing an innovative student curriculum based on standardized learning competencies identified by project participants, (c) revising the university curriculum to support such competencies, and (d) producing a practicum handbook. The project achieved its out-comes. Project conceptualization, implementation, and evaluation are discussed together with approaches for its replication.


[A prospective study to evaluate the safety of minor cutaneous surgery during aspirin treatment].
Many patients undergoing cutaneous surgery are treated with aspirin due to its proven advantages. Discontinuation of aspirin prior to surgery is still controversial. We conducted a large-scale, prospective study to evaluate the safety of dermatologic surgery in patients receiving aspirin. The authors' objectives were to evaluate the complication rate in patients undergoing cutaneous surgery while treated with aspirin. All patients operated on solely by one plastic surgeon were included in the study. The study group included all patients receiving aspirin during surgery, while the rest of the patients comprised the control group. Demographic data, surgery type and complication rate were collected. Complications were classified as major or minor hematoma, wound infection and dehiscence. Statistical significance was calculated using the Student's t-test and Chi test. During the study period 7259 patients underwent minor cutaneous surgery (without local flaps or skin grafts). A group of 115 patients taking either Plavix (Clopidrogel) or Coumadin (Warfarin) were excluded. The study group consisted of 1088 patients who were taking aspirin regularly while 6056 patients comprised the control group. A statistically significant change was found between the two groups regarding sex, age, background chronic diseases and in the distribution of lesions across the body. No significant change was found regarding the peri-operative complications. In this large-scale prospective study, dermatologic surgery on patients receiving aspirin was found to be safe, as no statistically different complication rate was found between the study and the control groups. This statement is further emphasized due to the significantly statistically older age, chronic illness rate and the head and neck location of the lesions in the study group.


Major recent and independent changes in levels and patterns of expression have occurred at the b gene, a regulatory locus in maize.
The b locus encodes a transcription factor that regulates the expression of genes that produce purple anthocyanin pigment. Different b alleles are expressed in distinct tissues, causing tissue-specific anthocyanin production. Understanding how phenotypic diversity is produced and maintained at the b locus should provide models for how other regulatory genes, including those that influence morphological traits and development, evolve. We have investigated how different levels and patterns of pigmentation have evolved by determining the phenotypic and evolutionary relationships between 18 alleles that represent the diversity of b alleles in Zea mays. Although most of these alleles have few phenotypic differences, five alleles have very distinct tissue-specific patterns of pigmentation. Superimposing the phenotypes on the molecular phylogeny reveals that the alleles with strong and distinctive patterns of expression are closely related to alleles with weak expression, implying that the distinctive patterns have arisen recently. We have identified apparent insertions in three of the five phenotypically distinct alleles, and the fourth has unique upstream restriction fragment length polymorphisms relative to closely related alleles. The insertion in B-Peru has been shown to be responsible for its unique expression and, in the other two alleles, the presence of the insertion correlates with the phenotype. These results suggest that major changes in gene expression are probably the result of large-scale changes in DNA sequence and/or structure most likely mediated by transposable elements.


[Human recombinant interferon-B constructed on the basis of affinity-binding domain technology].
Fusion gene consisting of dextran-binding domain from Leuconostoc mesenteroides subsp. Mesenteroides (DBD) and human recombinant interferon-beta (IFN-beta) incorporated between the nucleotide sequence encoding for the recognition site of human enteropeptidase (DDDDK) was installed and constructed in Escherichia coli. The overproducing strain of the chimeric protein DBD-IFN-beta consisting of the IFN-beta, spacer including 10 GS-repeats, human enteropeptidase recognition site, and dextran-binding domain from Leuconostoc mesenteroides was constructed. Free human recombinant interferon-beta was obtained as a result of treatment of the chimeric protein DBD-IFN-beta immobilized on sephadex G-25 with human enteropeptidase. The ability of free and immobilized protein to protect human cells from viral infection was demonstrated. The developed approach can be used for purification of the recombinant proteins with different biological activity and possible construction of new immunostimulating and antiviral drugs, growth factors, anti-cancer drugs, etc.


Critical care cardiovascular nurse expert and novice diagnostic cue utilization.
Critical care cardiovascular (CCCV) nursing diagnostic expertise was the focus of this research. The purpose of the study was to compare diagnostic cue utilization between expert and novice CCCV nurses. Knowledge related to objective measures of clinical nursing diagnostic expertise would enhance effective and efficient recognition, utilization, and reward of clinical expertise. Five CCCV written simulations served as instruments in the study. Diagnostic content areas included left ventricular dysfunction, cardiac tamponade, sepsis, right ventricular failure, and hypovolemia related to internal abdominal haemorrhage. The sample was composed of 23 expert and 23 novice nurses. After reading each simulation, subjects were asked to verbally recall the simulation, give an impression of the predominant problem or diagnosis, and give a diagnostic explanation. Verbal recalls were audio-taped for protocol analysis. Diagnostic accuracy and cue utilization were determined through comparisons of subjects' recalled diagnoses and cues with results from an expert panel review consensus. The major variable was the mean recalled proportion of highly relevant cues to total cues (HRC/TC) on accurately diagnosed simulations. Chi-square analysis revealed that diagnostic accuracy was greater with experts than with novices. Differences between and among simulations, expertise, accuracy and the mean proportion of highly relevant cues to total cues were examined with a 4 x 2 x 2 factorial analysis of variance. When considering all accurately diagnosed simulations, experts had a higher HRC/TC than novices. The major limitations were the use of low fidelity written simulations and virgin verbal protocol methods. The findings generally support the idea that the development of diagnostic expertise is associated with the ability to focus on highly relevant cues.


Ebstein Anomaly With Right Atrial Clot.
Ebstein anomaly (EA) is a rare congenital malformation of the tricuspid valve (TV), often associated with other cardiac malformations, especially atrial septal defect/patent foramen ovale (PFO) which is present in 80-90% of patients and predisposes to paradoxical embolization. We describe the case of a 17-year-old female, who presented with worsening exertional dyspnea, fatigue and pedal edema and atrial fibrillation (AF). Transthoracic echocardiography showed EA with severely dilated right atrium (RA), small functional right ventricle (RV), low velocity flow across TV with spontaneous echo contrast and giant clot in RA. Fortunately for the patient, contrast and transesophageal echocardiography revealed an intact interatrial septum with no PFO preventing any paradoxical embolism from large clot in RA, more so in the background of AF. Important differential diagnosis of congenitally unguarded TV orifice was ruled out due to presence of septal and anterior leaflets of TV and associated chordae.


The relationships of animal age and caloric intake to cellular replication in vivo and in vitro: a review.
This brief review examines aging at the cellular level as expressed by cell replication rates in vivo, clone size limits in vitro, and cell function in several tissues and organs. Studies are presented in which in vivo and in vitro cell replication measurements were made for several cell types and organs in relation to animal age, diet, life span, and specific age-related pathologies. Among the events examined that affect cell replication and cell survival in vitro and in vivo over a lifetime are oxidative damage, telomere shortening, and hormone and hormone receptor level changes. Long-term caloric restriction (CR) is favorable or protective for all of these events when measured in later life and comparisons are made to ad libitum (AL)-fed animals, and it is accompanied by more youthful rates of cell replication. It is proposed that in vivo and in vitro measures of cellular replication constitute biomarkers of aging when applied to comparisons of CR and AL diet rodents, where they correlate with the delay of disease and extension of life span. Longitudinal studies are needed to confirm this. The occurrence of certain age-related pathophysiologic states, such as immune (T cell) insufficiency, cataract, and senile osteopenia/osteoporosis, are accompanied by major diminishments of replication rates, numbers, and functions of the essential cell types in the organs and tissues involved. However, direct evidence is lacking that diminished cell replication in specific organs contributes to the limitation of life span.


Systematic review of diagnostic methods for acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is currently diagnosed by the Berlin definition, which does not include a direct measure of pulmonary oedema, endothelial permeability or pulmonary inflammation. We hypothesised that biomarkers of these processes have good diagnostic accuracy for ARDS. Medline and Scopus were searched for original diagnostic studies using minimally invasive testing. Primary outcome was the diagnostic accuracy per test and was categorised by control group. The methodological quality was assessed with QUADAS-2 tool. Biomarkers that had an area under the receiver operating characteristic curve (AUROCC) of >0.75 and were studied with minimal bias against an unselected control group were considered to be promising. Forty-four articles were included. The median AUROCC for all evaluated tests was 0.80 (25th to 75th percentile: 0.72-0.88). The type of control group influenced the diagnostic accuracy (p=0.0095). Higher risk of bias was associated with higher diagnostic accuracy (AUROCC 0.75 for low-bias, 0.77 for intermediate-bias and 0.84 for high-bias studies; p=0.0023). Club cell protein 16 and soluble receptor for advanced glycation end-products in plasma and two panels with biomarkers of oxidative stress in breath showed good diagnostic accuracy in low-bias studies that compared ARDS patients to an unselected intensive care unit (ICU) population. This systematic review revealed only four diagnostic tests fulfilling stringent criteria for a promising biomarker in a low-bias setting. For implementation into the clinical setting, prospective studies in a general unselected ICU population with good methodological quality are needed.


Do early onset conduct disordered adolescents perform like brain injured or normal adolescents on cognitive tests?
In order to better understand whether adolescents with early onset conduct disorder are predisposed to this disorder because of neurological problems, the present study compared the performance of early onset conduct disordered adolescents to adolescents with left hemisphere and right hemisphere brain injuries and normal controls. It was hypothesized that adolescents with early onset conduct disorder would perform similar to adolescents with left hemisphere injury, confirming theories that neurological dysfunction may predispose children to the development of conduct disorder. Fifteen adolescents with conduct disorder were compared on a battery of cognitive tests to 12 left hemisphere brain injured, 11 right hemisphere brain injured, and 15 normal middle school adolescents. F-tests indicated that there were significant differences among the four groups on all measures (p < .01). According to a series of t-tests on each of the nine cognitive measures, there were no differences found between the early onset conduct disordered subjects and the left hemisphere subjects. The early onset conduct disordered group performed worse than the right hemisphere group on 7 of the 9 comparisons, and worse than the normals on 9 of 9 comparisons. The normal group performed better than all three of the other groups. These results demonstrate that the pattern of neuropsychological performance by early onset conduct disordered adolescents was similar to that of left hemisphere injured adolescents and different from that of the right hemisphere injured and normal adolescents. Potential applications of this research include describing new approaches to treatment of this disorder based on their similarity with the left hemisphere brain injured group.


Coal ash conversion into effective adsorbents for removal of heavy metals and dyes from wastewater.
Fly ash was modified by hydrothermal treatment using NaOH solutions under various conditions for zeolite synthesis. The XRD patterns are presented. The results indicated that the samples obtained after treatment are much different. The XRD profiles revealed a number of new reflexes, suggesting a phase transformation probably occurred. Both heat treatment and chemical treatment increased the surface area and pore volume. It was found that zeolite P would be formed at the conditions of higher NaOH concentration and temperature. The treated fly ash was tested for adsorption of heavy metal ions and dyes in aqueous solution. It was shown that fly ash and the modified forms could effectively absorb heavy metals and methylene blue but not effectively adsorb rhodamine B. Modifying fly ash with NaOH solution would significantly enhance the adsorption capacity depending on the treatment temperature, time, and base concentration. The adsorption capacity of methylene blue would increases with pH of the dye solution and the sorption capacity of FA-NaOH could reach 5 x 10(-5) mol/g. The adsorption isotherm could be described by the Langmuir and Freundlich isotherm equations. Removal of copper and nickel ions could also be achieved on those treated fly ash. The removal efficiency for copper and nickel ions could be from 30% to 90% depending on the initial concentrations. The increase in adsorption temperature will enhance the adsorption efficiency for both heavy metals. The pseudo second-order kinetics would be better for fitting the dynamic adsorption of Cu and Ni ions.


Screening of Potential Biomarkers in the Peripheral Serum for Steroid-Induced Osteonecrosis of the Femoral Head Based on WGCNA and Machine Learning Algorithms.
Steroid-induced osteonecrosis of the femoral head (SONFH) has produced a substantial burden of medical and social experience. However, the current diagnosis is still limited. Thus, this study is aimed at identifying potential biomarkers in the peripheral serum of patients with SONFH. The expression profile data of SONFH (number: GSE123568) was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in SONFH were identified and used for weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological functions. The protein-protein interaction (PPI) network and machine learning algorithms were employed to screen for potential biomarkers. Gene set enrichment analysis (GSEA), transcription factor (TF) enrichment analysis, and competing endogenous RNA (ceRNA) network were used to determine the biological functions and regulatory mechanisms of the potential biomarkers. A total of 562 DEGs, including 318 upregulated and 244 downregulated genes, were identified between SONFH and control samples, and 94 target genes were screened based on WGCNA. Moreover, biological function analysis suggested that target genes were mainly involved in erythrocyte differentiation, homeostasis and development, and myeloid cell homeostasis and development. Furthermore, GYPA, TMCC2, and BPGM were identified as potential biomarkers in the peripheral serum of patients with SONFH based on machine learning algorithms and showed good diagnostic values. GSEA revealed that GYPA, TMCC2, and BPGM were mainly involved in immune-related biological processes (BPs) and signaling pathways. Finally, we found that GYPA might be regulated by hsa-miR-3137 and that BPGM might be regulated by hsa-miR-340-3p. GYPA, TMCC2, and BPGM are potential biomarkers in the peripheral serum of patients with SONFH and might affect SONFH by regulating erythrocytes and immunity.


Regulation of light-harvesting chlorophyll protein biosynthesis in greening seedlings : a species comparison.
The biosynthesis of the chlorophyll a/b binding protein associated with photosystem II (LHC-II) was characterized during light-induced greening of etiolated barley (Hordeum vulgare [L.] cv Boone), maize (Zea mays [L.] Pioneer 3148), pea (Pisum sativum [L.] cv Progress 9), and soybean (Glycine max [L.] Merr. cv Ransom 2). Northern blot analysis revealed that pea LHC-II mRNA was present in dark-grown seedlings and accumulated rapidly within 1 hour following illumination with white light. In contrast, the accumulation of LHC-II mRNA was delayed in barley and soybean until 2 to 4 hours after illumination began. Single radial immunodiffusion analysis revealed that LHC-II polypeptides began to accumulate in all species between 4 and 8 hours although the protein was present in detectable levels at earlier times in certain species. In a pattern similar to the LHC-II protein accumulation, chlorophyll accumulated at increased rates between 4 and 8 hours of greening in all species following an initial delay. The absence of coordination between LHC-II mRNA and LHC-II protein accumulation that was clearly observed in pea suggested that transcription is not the factor that limits LHC-II complex formation during chloroplast development. The accumulation of chlorophyll and LHC-II protein appeared to coincide suggesting that chlorophyll biosynthesis may be a factor that limits LHC-II complex formation.


Role of glutathione in detoxification of copper and cadmium by yeast cells having different abilities to express cup1 protein.
ABSTRACT Although copper is an essential metal and cadmium is an environmental pollutant, both are toxic when present in excess. Metallothionein and glutathione are two of the key components that participate in detoxification of copper and cadmium. In the present study the role of glutathione in resistance to copper and cadmium was investigated with the yeast Saccharomyces cerevisiae. The yeast cells used in this study have different abilities to produce glutathione and Cup1 protein, the yeast metallothionein homolog encoded by CUP1 gene. It was demonstrated that Cup1 protein plays a dominant role in buffering excess copper, and yeast does not depend on glutathione to reduce copper toxicity whether it possesses single or multiple copies of CUP1. In fact, excess copper can cause glutathione oxidation and depletion and damage the glutathione system. On the other hand, it was indicated that Cup1 protein is an important cadmium-detoxifying component, and the glutathione system can positively respond to cadmium. In yeast containing single or multiple copies of CUP1, glutathione is an indispensable line of defense against cadmium. Yeast having glutathione and no Cup1 protein is not able to grow in medium containing excess copper, but can tolerate higher concentrations of cadmium. In addition, it was found that yeast, independent of glutathione, can efficiently remove excess copper, whereas it cannot promptly eliminate accumulated cadmium regardless of having glutathione or not.


Recurrent pericarditis in an adolescent with Crohn's colitis.
Extraintestinal manifestations are common complications of inflammatory bowel disease (IBD), whereas the recurrent pericarditis during remission of Crohn's disease is rarely reported. Chest pain developed in a 13-year-old adolescent male who had a history of Crohn's colitis since 9 years of age and was in remission for 4 years after treatment with infliximab, adalimumab, and vedolizumab. Physicians should be aware of the pericardial involvement in patients with a history of IBD. The literature on pericardial involvement in Crohn's disease is reviewed with emphasis on the management of recurrent pericardial effusion in the pediatric age group.


Noise in MTF Measurements.
The effect of shot noise on the MTF of a lens when measured by means of an edge scan is treated both analytically and experimentally. It is shown that the variance in the MTF, introduced by the shot noise, establishes an upper bound on the magnitude of any systematic error introduced into the MTF measurement by the noise. Both the variance and the systematic bias in the MTF measurement due to the noise can be reduced to arbitrarily small values by controlling the electrical bandwidth and the scanner velocity. Expressions are given for the maximum scanner velocity and the minimum elapsed time for the scan as a function of the acceptable variance.


Procedure for computer-controlled milling of accurate surfaces of revolution for millimeter and far-infrared mirrors.
We discuss a simple method for milling accurate off-axis parabolic mirrors with a computer-controlled milling machine. For machines with a built-in circle-cutting routine, an exact paraboloid can be milled with few computer commands and without the use of the spherical or linear approximations that have been discussed in other mirror-cutting procedures in the literature. The method given here can be adapted easily to cut offaxis sections of elliptical or spherical mirrors.


Child maltreatment data: A summary of progress, prospects and challenges.
In 1996, the ISPCAN Working Group on Child Maltreatment Data (ISPCAN-WGCMD) was established to provide an international forum in which individuals, who deal with child maltreatment data in their respective professional roles, can share concerns and solutions. This commentary describes some of the key features and the status of child maltreatment related data collection addressed by the ISPCAN-WGCMD. Different types of data collection methods including self-report, sentinel, and administrative data designs are described as well as how they address different needs for information to help understand child maltreatment and systems of prevention and intervention. While still lacking in many parts of the world, access to child maltreatment data has become much more widespread, and in many places a very sophisticated undertaking. The ISPCAN-WGCMD has been an important forum for supporting the continued development and improvement in the global effort to understand and combat child maltreatment thus contributing to the long term goals of the UN Convention on the Rights of the Child. Nevertheless, based on what has been learned, even greater efforts are required to improve data in order to effectively combat child maltreatment.


Monoclinic α-Na2FePO4F with Strong Antisite Disorder and Enhanced Na+ Diffusion.
A new monoclinic α-polymorph of the Na2FePO4F fluoride-phosphate has been directly synthesized via a hydrothermal method for application in metal-ion batteries. The crystal structure of the as-prepared α-Na2FePO4F studied with powder X-ray and neutron diffraction (P21/c, a = 13.6753(10) Å, b = 5.2503(2) Å, c = 13.7202(8) Å, β = 120.230(4)°) demonstrates strong antisite disorder between the Na and Fe atoms. As revealed with DFT-based calculations, α-Na2FePO4F has low migration barriers for Na+ along the main pathway parallel to the b axis, and an additional diffusion bypass allowing the Na+ cations to go around the Na/Fe antisite defects. These results corroborate with the extremely high experimental Na-ion diffusion coefficient of (1-5)·10-11 cm2·s-1, which is 2 orders of magnitude higher than that for the orthorhombic β-polymorph ((5-10)·10-13 cm2·s-1). Being tested as a cathode material in Na- and Li-ion battery cells, monoclinic α-Na2FePO4F exhibits a reversible specific capacity of 90 and 80 mAh g-1, respectively.


Conserved mutations in the pneumococcal bacteriocin transporter gene, blpA, result in a complex population consisting of producers and cheaters.
All fully sequenced strains of Streptococcus pneumoniae possess a version of the blp locus, which is responsible for bacteriocin production and immunity. Activation of the blp locus is stimulated by accumulation of the peptide pheromone, BlpC, following its secretion by the ABC transporter, BlpA. The blp locus is characterized by significant diversity in blpC type and in the region of the locus containing putative bacteriocin and immunity genes. In addition, the blpA gene can represent a single large open reading frame or be divided into several smaller fragments due to the presence of frameshift mutations. In this study, we use a collection of strains with blp-dependent inhibition and immunity to define the genetic changes that bring about phenotypic differences in bacteriocin production or immunity. We demonstrate that alterations in blpA, blpC, and bacteriocin/immunity content likely play an important role in competitive interactions between pneumococcal strains. Importantly, strains with a highly conserved frameshift mutation in blpA are unable to secrete bacteriocins or BlpC, but retain the ability to respond to exogenous peptide pheromone produced by cocolonizing strains, stimulating blp-mediated immunity. These "cheater" strains can only coexist with bacteriocin-producing strains that secrete their cognate BlpC and share the same immunity proteins. The variable outcome of these interactions helps to explain the heterogeneity of the blp pheromone, bacteriocin, and immunity protein content. Streptococcus pneumoniae resides in a polymicrobial environment and competes for limited resources by the elaboration of small antimicrobial peptides called bacteriocins. A conserved cluster of genes in the S. pneumoniae genome is involved in the production of bacteriocins and their associated protective immunity proteins through secretion of a signaling pheromone. In this study, we show that a significant number of strains have lost the ability to secrete bacteriocins and signaling pheromones due to a specific mutation in a dedicated transporter protein. Because the regulatory and immunity portion of the locus is retained, these "cheater" strains can survive in the face of invasion from a bacteriocin-producing strain without the cost of bacteriocin secretion. The outcome of such interactions depends on each strain's repertoire of pheromone, immunity protein, and bacteriocin genes, such that intrastrain competition drives the diversity in bacteriocin, immunity protein, and pheromone content.


Activation of the transcription factor kappa B in human KG-1 myeloid leukemia cells treated with 1-beta-D-arabinofuranosylcytosine.
The present studies have examined the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) on activation of the transcription factor kappa B (NF-kappa B). The results demonstrate that treatment of human KG-1 myeloid leukemia cells with ara-C is associated with induction of protein binding to the NF-kappa B consensus sequence. NF-kappa B binding was activated at 30 min and reached maximal levels of binding at 1-2 hr of ara-C treatment. The NF-kappa B consensus sequence was ligated to the heterologous thymidine kinase (TK) promoter and the human growth hormone (GH) reporter gene to determine whether ara-C-induced NF-kappa B activity includes an enhancer function. Ara-C treatment had little effect on transient expression of pTKGH in KG-1 cells but increased transcription of the p (NF-kappa B) TKGH vector by 8-fold. The results also demonstrate that ara-C transiently increases NF-kappa B mRNA levels. However, the finding that ara-C-induced binding of NF-kappa B to DNA occurs in the presence of cycloheximide indicates that this agent activates preexisting NF-kappa B protein. These results suggest that ara-C induces a cytoplasmic pathway that transduces signals to the nucleus by activation of NF-kappa B.


The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford.
The Fluorescence Activated Cell Sorter (FACS) was invented in the late 1960s by Bonner, Sweet, Hulett, Herzenberg, and others to do flow cytometry and cell sorting of viable cells. Becton Dickinson Immunocytometry Systems introduced the commercial machines in the early 1970s, using the Stanford patent and expertise supplied by the Herzenberg Laboratory and a Becton Dickinson engineering group under Bernie Shoor. Over the years, we have increased the number of measured FACS dimensions (parameters) and the speed of sorting to where we now simultaneously measure 12 fluorescent colors plus 2 scatter parameters. In this history, I illustrate the great utility of this state-of-the-art instrument, which allows us to simultaneously stain, analyze, and then sort cells from small samples of human blood cells from AIDS patients, infants, stem cell transplant patients, and others. I also illustrate analysis and sorting of multiple subpopulations of lymphocytes by use of 8-12 colors. In addition, I review single cell sorting used to clone and analyze hybridomas and discuss other applications of FACS developed over the past 30 years, as well as give our ideas on the future of FACS. These ideas are currently being implemented in new programs using the internet for data storage and analysis as well as developing new fluorochromes, e.g., green fluorescent protein and tandem dyes, with applications in such areas as apoptosis, gene expression, cytokine expression, cell biochemistry, redox regulation, and AIDS. Finally, I describe new FACS methods for measuring activated kinases and phosphatases and redox active enzymes in individual cells simultaneously with cell surface phenotyping. Thus, key functions can be studied in various subsets of cells without the need for prior sorting.


Glucose control in the intensive care unit: a nutrition support perspective.
Hyperglycemia commonly occurs in acutely ill patients who receive nutrition support, even in patients without a history of diabetes. The traditional view that stress hyperglycemia may be a beneficial adaptive response has been replaced by data linking hyperglycemia with increased morbidity and mortality in critically ill populations. Initial randomized studies to control stress hyperglycemia with intensive insulin infusion reported dramatic decreases in infectious complications and decreased mortality. However, recent large multicenter trials have reported that intensive insulin therapy designed to normalize blood glucose resulted in an unacceptable increase in the incidence of hypoglycemia. Review of the methods, protocols, and nutrition provided during these randomized studies is crucial to understanding the different conclusions reached and how these results may be used to influence protocols in intensive care units today. Evidence is reviewed and practical considerations are provided for nutrition support regimens to minimize stress hypoglycemia and assist glucose management.


Negative symptoms, trauma, and autobiographical memory: an investigation of individuals recovering from psychosis.
Psychological research on negative symptoms in schizophrenia is scarce. The aim of this study was to explore the relationship between negative symptoms and trauma in individuals recovering from a psychotic illness. Specifically, the aim was to examine the association between negative symptoms and traumatic reactions to psychosis and to hospitalization. We were also interested in the association between traumatic reactions and autobiographical memory. The design was a cross-sectional investigation of 38 people recovering from functional psychotic illness. Hypotheses were examined using correlations between measures of negative symptoms, posttraumatic avoidance, and specificity of autobiographical retrieval. Negative symptoms were found to be significantly associated with avoidance of traumatic memories related to psychosis and hospitalization and with a lack of specificity in autobiographical recall. Further analysis showed that avoidance related to psychosis and low specificity in recall were significant predictors of negative symptoms. These data suggest that people who avoid traumatic memories of psychosis and hospitalization have more negative symptoms and retrieve fewer specific autobiographical memories. The possibility that negative symptoms may be reactive is explored, along with the implications for our theoretical and clinical understanding. The methodological limitations of the study and ideas for future research are discussed.


Implications of mouse genotype for phenotype.
Genetic engineering of inbred mice offers the capability to separate interactions of multiple genes that control host resistance to pathogens. An understanding of the negative impact that genetic variability of mouse substrains can have on data is necessary for the design of experiments to dissect out complicated gene interactions.


Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis.
Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5-year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.


Aesthetic Preferences of the Anterior Thigh as a Beauty Factor in Women.
In body contouring surgery, some regions, such as the abdomen, thorax, upper limbs, and glutes, are prioritized over others, including the lower limbs, particularly the anterior thighs. This study aimed to identify anterior thigh preferences by age, sex, ethnicity, and region and assess their importance as a factor of female beauty by conducting an online survey. Photographs of a 24-year-old female model were modified in two front-view and side-view panels. Through a survey on the Amazon Mechanical Turk platform, participants were asked to order the images from the most beautiful to the least beautiful, and the results were broken down by age, sex, ethnicity, and region. A total of 1000 respondents were surveyed, all of whom answered the survey without error; therefore, no one was excluded. Of the 1000 respondents, 504 were men (50.4%) and 496 were women (49.6%). The predominant age group was 26-35 years, with 443 people (44.3%), the region with the highest number of participants was North America, with 484 respondents (48.4%), and the predominant ethnicity was White, with 555 respondents (55.5%). The survey showed that the most beautiful images were image A on the side-view panel (25.9%) and image I on the front-view panel (28.5%)(P < 0.001). In the side view, the aesthetic preferences of the anterior thigh do not appear to be associated with the anterior projection. However, in the front view, the increase in width generates a beauty trend, but only up to an intermediate level, quantified in the ratio (0.44).


Quantification of the variability in response to propofol administration in children.
Closed-loop control of anesthesia is expected to decrease drug dosage and wake up time while increasing patient safety and decreasing the work load of the anesthesiologist. The potential of closed-loop control in anesthesia has been demonstrated in several clinical studies. One of the challenges in the development of a closed-loop system that can be widely accepted by clinicians and regulatory authorities is the effect of interpatient variability in drug sensitivity. This system uncertainty may lead to unacceptable performance, or even instability of the closed-loop system for some individuals. The development of reliable models of the effect of anesthetic drugs and characterization of the uncertainty is, therefore, an important step in the development of a closed-loop system. Model identification from clinical data is challenging due to limited excitation and the lack of validation data. In this paper, approximate models are validated for controller design by evaluating the predictive accuracy of the closed-loop behavior. A set of 47 validated models that describe the interpatient variability in the response to propofol in children is presented. This model set can be used for robust linear controller design provided that the experimental conditions are similar to the conditions during data collection.


Increased thermal deactivation of excited pigments in pea leaves subjected to photoinhibitory treatments.
The photoacoustic technique was used to monitor thermal deexcitation of the photosynthetic pigments in intact pea leaves (Pisum sativum L.) submitted to photoinhibitory treatments. When the leaves were exposed to photon flux densities above 1000 micromoles per square meter per second, the amplitude of the photothermal component of the in vivo photoacoustic signal strongly increased. This high-light-induced stimulation of nonradiative energy dissipation (heat emission) was accompanied by an inverse change in the O(2) evolution activity and in the steady state emission of 685 nanometer chlorophyll fluorescence. The time course of these effects was shown to be very rapid, with a t(1/2) of around 15 minutes. When high-light-treated leaves were readapted to the dark, the heat emission changes were reversed, following somewhat slower kinetics. A reversible increase in the rate of light energy dissipation via radiationless transitions could be a photoprotective mechanism eliminating excess excitation energy from the photosynthetic reaction centers. Interestingly, this process does not operate at temperatures below about 12 degrees C.


Disrupted microRNA expression caused by Mecp2 loss in a mouse model of Rett syndrome.
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate post-transcriptional gene expression. They influence a wide range of physiological functions, including neuronal processes, and are regulated by various mechanisms, such as DNA methylation. This epigenetic mark is recognized by transcriptional regulators such as the methyl CpG binding protein Mecp2. Rett syndrome is a complex neurological disorder that has been associated with mutations in the gene coding for Mecp2. Thus, we examined the possible miRNA misregulation caused by Mecp2 absence in a mouse model of Rett syndrome. Using miRNA expression microarrays, we observed that the brain of Rett syndrome mice undergoes a disruption of the expression profiles of miRNAs. Among the significantly altered miRNAs (26%, 65 of 245), overall downregulation of these transcripts was the most common feature (71%), whilst the remaining 30% were upregulated. Further validation by quantitative RT-PCR demonstrated that the most commonly disrupted miRNAs were miR-146a, miR-146b, miR-130, miR-122a, miR-342 and miR-409 (downregulated), and miR-29b, miR329, miR-199b, miR-382, miR-296, miR-221 and miR-92 (upregulated). Most importantly, transfection of miR-146a in a neuroblastoma cell line caused the downregulation of IL-1 receptor-associated kinase 1 (Irak1) levels, suggesting that the identified defect of miR-146a in Rett syndrome mice brains might be responsible for the observed upregulation of Irak1 in this model of the human disease. Overall, we provide another level of molecular deregulation occurring in Rett syndrome that might be useful for understanding the disease and for designing targeted therapies.


Analytical strategy coupled to chemometrics to differentiate Camellia sinensis tea types based on phenolic composition, alkaloids, and amino acids.
Catechins, amino acids, and alkaloids are primary chemical components of tea and play a crucial role in determining tea quality. Their composition and content largely vary among different types of tea. In this study, a convenient chemical classification method was developed for six Camellia sinensis tea types (white, green, oolong, black, dark, and yellow) based on the quantification of their major components. Twenty-one free amino acids, 6 catechins, 2 alkaloids, and gallic acid in 24 teas were quantified using ultra-high-performance liquid chromatography (UHPLC). The total catechin contents in these tea samples ranged from 10.96 to 95.67 mg/g, while total free amino acid content ranged from 2.63 to 25.89 mg/g. Theanine (Thea) was the most abundant amino acid in all tea varieties. Catechin and amino acid levels in tea were markedly reduced upon fermentation of tea. Furthermore, high-temperature processing (roasting) during tea production induced degradation and epimerization of catechins, yielding epimerized catechins, simple catechins, and gallic acid. Principal component analysis revealed that major ester-catechins (EGCG and ECG), major amino acids (Thea), and major alkaloids (caffeine) are potential factors for distinguishing different types of tea. Linear discriminant analysis showed that 100% of teas were correctly classified in which (+)-catechin, ECG, EGC, gallic acid, GABA, cysteine, lysine, and threonine were the most discriminating compounds. This study shows that quantification of the major tea components combined with chemometric analysis, can serve as a simple, convenient, and reliable approach for classifying tea according to fermentation level. PRACTICAL APPLICATION: Different Camellia sinensis tea types can be produced worldwide but it is still challenging to know which chemical markers can be used to trace their production. in this paper we used a targeted methodology to classify six tea types (white, green, oolong, black, dark, and yellow) based on phenolic composition, alkaloids, and amino acids. The main chemical markers responsible for the discrimination were pinpointed with the use of chemometric tools.


Doing Family in "Times of Migration": Care Temporalities and Gender Politics in Southeast Asia.
The prevailing labor migration regime in Asia is underpinned by rotating-door principles of enforced transience, where low-wage migrant labor gains admission into host nation-states based on short-term, time-limited contracts and where family reunification and permanent settlement at destination are explicitly prohibited. In this context, we ask how migrant-sending families in Southeast Asian "source" countries-Indonesia and the Philippines-sustain family life in the long-term absence of one or both parents (often mothers). Through temporal concepts of rhythm, rupture, and reversal, we focus on how temporal modalities of care for left-behind children intersect with gendered power geometries in animating transnational family politics around care. First, by paying heed to the structuring effects of rhythm on social life, we show how routinized care rhythms built around mothers as caregivers have a normalizing and naturalizing effect on the conduct of social life and commonplace understanding of family well-being. Second, we explore the potential rupture to care rhythms triggered by the migration of mothers turned breadwinners and the extent to which gendered care regimes are either conserved, reconstituted, or disrupted in everyday patterns and practices of care. Third, we examine the circumstances under which gender role reversal becomes enduring, gains legitimacy among a range of poly care rhythms, or is quickly undone with the return migration of mothers in homecoming. The analysis is based primarily on research on Indonesian and Filipino rural households conducted in 2017 using paired life story interviews with children and their parental or nonparental adult caregivers.


Metabolic rate changes proportionally to circadian frequency in tau mutant Syrian hamsters.
The tau mutation in Syrian hamsters (Mesocricetus auratus) is phenotypically expressed in a period of the circadian rhythm of about 20 h in homozygotes (SS) and about 22 h in heterozygotes (S+). The authors investigate whether this well-defined model for variation in circadian period exhibits associated changes in energy metabolism. In hamsters of the three genotypes (SS, S+, and wild type [WT]), oxygen consumption measurements were performed at 28 degrees C (thermoneutral), 18 degrees C, and (after acclimatization) 10 degrees C. After correction for body mass, SS tau mutant hamsters had a higher overall metabolic rate (average oxygen consumption per hour over 24 h) and a higher resting metabolic rate (the lowest 30-min oxygen consumption in the subjective day) than did WT hamsters at all ambient temperatures. S+ hamsters were intermediate in both after taking body mass into account. The differences in metabolism among the three genotypes indicate that the increase in metabolic rate was statistically indistinguishable from a proportional increase in circadian frequency. The oxygen consumption totals per circadian cycle (24 h for WT, 22 h for S+, and 20 h for SS mutants) were not statistically different among the genotypes after correcting for body mass. The possible roles of pleiotropic effects, of linkage to genes involved in growth and metabolism, and of early ontogenetic influences are briefly discussed.


Repeat lumbar surgery. A review of patients with failure from previous lumbar surgery treated by spinal canal exploration and lumbar spinal fusion.
Thirty-six patients with chronic back and/or leg pain following previous lumbar surgery who underwent both spinal canal exploration and spinal fusion were subjected to retrospective review. The purpose was to determine the probability of success for this surgical approach. Twenty (56%) of the 36 patients had a satisfactory result. In 15 patients with multiple objective findings of an ongoing radiculopathy, 11 (73%) improved. Only nine (43%) of 21 patients improved if these preoperative criteria were absent. Analysis according to the type of surgery performed in the spinal canal demonstrated improvement in (a) 17 (74%) of 23 patients who had wide bony decompression, (b) eight (61%) of 12 patients who had discectomy, and (c) seven (47%) of 15 patients who had an extensive neurolysis. In 17 patients whose time interval between the previous operation and present reconstruction was greater than 18 months, 13 (76%) improved. Only seven (36%) of 19 patients with a shorter time interval improved. The presence of pseudarthrosis was a poor indication for repeat lumbar surgery. The number of previous lumbar surgeries may not necessarily preclude a satisfactory outcome. Solid fusion correlated highly with a satisfactory outcome. Best results are obtained when objective preoperative findings indicate the presence of a surgically correctable abnormality.


Muscarinic-receptor functioning in tracheas from normal and ovalbumin-sensitive guinea pigs.
Responses to bilateral vagal nerve stimulation, to field stimulation, and to exogenous methacholine and histamine were compared in tracheas isolated from (a) saline injected (i.p.) and saline-aerosol exposed guinea pigs (control), (b) ovalbumin-sensitized and saline-aerosol exposed (sensitized) guinea pigs, and (c) ovalbumin-sensitized and 2% ovalbumin-aerosol exposed (challenged) guinea pigs. Tracheal pressor responses (cmH2O; 1 cmH2O = 98.1 Pa) to nerve and field stimulation, and maximal responses to methacholine and histamine were significantly increased in animals from group c compared with groups a and b. Dose-response lines in response to the two agonists, expressed as percent maximal contraction, did not differ among the groups. The M1 antagonist pirenzepine (0.1-10 nM) selectively reduced responses to nerve stimulation in all three groups. The M2 antagonist gallamine potentiated responses to nerve or field stimulation in all three groups. We conclude that M1, M2, and M3 muscarinic receptor functioning is similar in control and ovalbumin-sensitized guinea pigs. Changes in post-receptor transduction mechanisms may mediate the increased responsiveness noted in animals from group c.


Hydroxyl radical formation and oxidative DNA damage induced by areca quid in vivo.
Chewing areca quid (AQ) has been implicated as a major risk factor for the development of oral squamous-cell carcinoma (OSCC). Recent studies have suggested that AQ-generated reactive oxygen species (ROS) is one of the contributing factors for oral carcinogenesis. However, the AQ used in Taiwan is different from that used in other countries. This study is designed to test whether ROS are generated and the consequent effects in locally prepared AQ in vivo. We measured the hydroxyl radical formation, as represented by the presence of o- and m-tyrosine in saliva from volunteers who chewed AQ containing 20 mg phenylalanine. Their saliva contained significantly higher amounts (p < .05) of o- and m-tyrosine as compared to the controls. In addition, chewing AQ containing Piper betle inflorescence generated higher amounts of m-tyrosine, but not o-tyrosine, in saliva than did chewing AQ containing betel leaf. We further tested the oxidative DNA damaging effect of the reconstituted AQ, as evidenced by the elevation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, in hamster buccal pouch. Following daily painting for 14 d, the 8-OH-dG level in hamster buccal pouch is significantly elevated (p < .05) in the AQ-treated group versus the controls. These findings demonstrate that ROS, such as hydroxyl radical, are formed in the human oral cavity during AQ chewing, and chewing such prepared AQ might cause oxidative DNA damage to the surrounding tissues.


Concerted action of the transcriptional activators REB1, RAP1, and GCR1 in the high-level expression of the glycolytic gene TPI.
In Saccharomyces cerevisiae, the TPI gene product, triosephosphate isomerase, makes up about 2% of the soluble cellular protein. Using in vitro and in vivo footprinting techniques, we have identified four binding sites for three factors in the 5' noncoding region of TPI: a REB1-binding site located at positions -401 to -392, two GCR1-binding sites located at positions -381 to -366 and -341 to -326, and a RAP1-binding site located at positions -358 to -346. We tested the effects of mutations at each of these binding sites on the expression of a TPI::lacZ gene fusion which carried 853 bp of the TPI 5' noncoding region integrated at the URA3 locus. The REB1-binding site is dispensable when material 5' to it is deleted; however, if the sequence 5' to the REB1-binding site is from the TPI locus, expression is reduced fivefold when the site is mutated. Because REB1 blocks nucleosome formation, the most likely function of its binding site in the TPI controlling region is to prevent the formation of nucleosomes over the TPI upstream activation sequence. Mutations in the RAP1-binding site resulted in a 10-fold reduction in expression of the reporter gene. Mutating either GCR1-binding site alone had a modest effect on expression of the fusion. However, mutating both GCR1-binding sites resulted in a 68-fold reduction in the level of expression of the reporter gene. A LexA-GCR1 fusion protein containing the DNA-binding domain of LexA fused to the amino terminus of GCR1 was able to activate expression of a lex operator::GAL1::lacZ reporter gene 116-fold over background levels. From this experiment, we conclude that GCR1 is able to activate gene expression in the absence of REB1 or RAP1 bound at adjacent binding sites. On the basis of these results, we suggest that GCR1 binding is required for activation of TPI and other GCR1-dependent genes and that the primary role of other factors which bind adjacent to GCR1-binding sites is to facilitate of modulate GCR1 binding in vivo.


Changes in the cellular energy state affect the activity of the bacterial phosphotransferase system.
The effect of different cellular free-energy states on the uptake of methyl alpha-D-glucopyranoside, an analogue of glucose, by the Escherichia coli phosphoenolpyruvate:carbohydrate phosphotransferase system was investigated. The intracellular [ATP]/[ADP] ratio was varied by changing the expression of the atp operon, which codes for the H+-ATPase, or by adding an uncoupler of oxidative phosphorylation or an inhibitor of respiration. Corresponding initial phosphotransferase uptake rates were determined using an improved uptake assay that works with growing cells in steady state. The results show that the initial uptake rate was decreased under conditions of lowered intracellular [ATP]/[ADP] ratios, irrespective of which method was used to change the cellular energy state. When either the expression of the atp operon was changed or 2,4-dinitrophenol was added to wild-type cells, the relationship between initial phosphotransferase uptake rate and the logarithm of the [ATP]/[ADP] ratio was approximately linear. These results suggest that the cellular free-energy state, as reflected in the intracellular [ATPI]/[ADP] ratio, plays an important role in regulating the activity of the phosphotransferase system.


Diurnal variation of dimethylallyl diphosphate concentrations in oak (Quercus robur) leaves.
In the present work a rapid and sensitive non-radioactive assay for the determination of cellular dimethylallyl diphosphate (DMADP) was developed and used for the analysis of the diurnal variation of DMADP levels in oak leaves. The method is based on the acid-catalysed hydrolysis of DMADP to isoprene, which subsequently is determined by gas chromatography. Diurnal variation of cellular DMADP levels in oak leaves of young saplings was measured on 6 days in 1998 and 1999, showing a 2 to 3-fold light-dependent increase from approximately 15 pmol mg-1 DW in the night to 31-75 pmol mg-1 DW around noon. The leaf DMADP contents showed a significant positive correlation with net assimilation and isoprene emission rates, indicating that the availability of cellular DMADP might be an important regulatory factor of leaf isoprene emission.


Sex hormone receptors in human thyroid tissues.
The behavior of sex hormone receptors was studied in the cytosol of thyroid tissue samples in order to clarify the effects of sex hormones on diseases of the thyroid. Androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PgR) were assayed using the dextran-coated charcoal (DCC) method and analyzed by the method of Scatchard. Androgen receptor, ER, and PgR were negative in all of the cytosol prepared from normal thyroid tissues. However, the positive rates for the receptors in the neoplastic and nonneoplastic tissues were 22% for AR, 29% for ER, and 18% for PgR. Especially, the incidence of ER was significantly higher in neoplastic lesions than normal tissues. These data suggest that sex hormones, especially estrogen, may play a role in diseases of the thyroid.


17O Labeling Reveals Paired Active Sites in Zeolite Catalysts.
Current needs for extending zeolite catalysts beyond traditional gas-phase hydrocarbon chemistry demand detailed characterization of active site structures, distributions, and hydrothermal impacts. A broad suite of homonuclear and heteronuclear NMR correlation experiments on dehydrated H-ZSM-5 catalysts with isotopically enriched 17O frameworks reveals that at least two types of paired active sites exist, the amount of which depends on the population of fully framework-coordinated tetrahedral Al (Al(IV)-1) and partially framework-coordinated tetrahedral Al (Al(IV)-2) sites, both of which can be denoted as (SiO)4-n-Al(OH)n. The relative amounts of Al(IV)-1 and Al(IV)-2 sites, and subsequent pairing, cannot be inferred from the catalyst Si/Al ratio, but depend on synthetic and postsynthetic modifications. Correlation experiments demonstrate that, on average, acidic hydroxyl groups from Al(IV)-1/Al(IV)-2 pairs are closer to one another than those from Al(IV)-1/Al(IV)-1 pairs, as supported by computational DFT calculations. Through-bond and through-space polarization transfer experiments exploiting 17O nuclei reveal a number of different acidic hydroxyl groups in varying Si/Al catalysts, the relative amounts of which change following postsynthetic modifications. Using room-temperature isotopic exchange methods, it was determined that 17O was homogeneously incorporated into the zeolite framework, while 17O → 27Al polarization transfer experiments demonstrated that 17O incorporation does not occur for extra-framework AlnOm species. Data from samples exposed to controlled hydrolysis indicates that nearest neighbor Al pairs in the framework are more susceptible to hydrolytic attack. The data reported here suggest that Al(IV)-1/Al(IV)-2 paired sites are synergistic sites leading to increased reactivity in both low- and high-temperature reactions. No evidence was found for paired framework/nonframework sites.


Thromboprophylaxis and Outcomes for Total Joint Arthroplasty in Congenital Bleeding Disorders: A Single-Center Experience.
Total joint arthroplasty (TJA) improves the quality of life for patients with end-stage osteoarthritis but is associated with an increased risk of venous thromboembolism (VTE), thus pharmacologic thromboprophylaxis is recommended for most patients. Patients with congenital bleeding disorders may develop severe arthropathies due to repeated hemarthroses and derive similar benefit from TJA as the general population. No guidelines for pharmacologic thromboprophylaxis in this population exist, however, as the risks and benefits are not well defined. We undertook the current study to assess the safety and efficacy of pharmacologic VTE prophylaxis in patients with congenital bleeding disorders undergoing TJA. We retrospectively reviewed the medical records of patients with bleeding disorders who underwent TJA at our academic institution between 1987 and 2012. We identified 28 patients who underwent 38 TJA procedures. Low-molecular-weight heparin (LMWH) was administered in 29 procedures (76%) and was discontinued early in 3 procedures (2 patients) due to nonjoint bleeding. No symptomatic VTE was identified, and no joint or deep wound infections were seen. Twenty-two patients accounting for 31 procedures were contacted to discuss their experience with TJA. All reported decreased pain, and 97% reported improved function after the surgery. Impressively, 97% stated that they would choose to have the surgery again. These results confirm the benefit of TJA in patients with congenital bleeding disorders and end-stage arthropathies and suggest that LMWH thromboprophylaxis is safe. No patient in our cohort developed symptomatic VTE, whether or not thromboprophylaxis was administered, thus necessity of thromboprophylaxis remains an unanswered question.


Combined epidural and general anesthesia in aortic surgery.
The perioperative course of 144 consecutive patients undergoing aortic reconstructive surgery was studied to assess the potential benefit of employing a combined epidural and light general anesthesia technique. A group of 67 patients had general anesthesia alone (GA), while in the group of 77 remaining patients, a combined epidural and general anesthesia (Epi-GA) was employed. The two groups were similar in regards to age, medical risk factors, preoperative assessment of cardiac and pulmonary function, and type of surgical reconstruction. There was no significant difference in the anesthetic, operative time, or operative fluid requirements between the two groups. There was a lower rate pressure product in the Epi-GA group during aortic cross clamping (P less than 0.05). More patients in the GA group required a prolonged ventilatory support (P less than 0.05) and a high parenteral narcotic administration (P less than 0.025) during the first 48 hours. While the mortality rate was similar for the two groups (3.0% for GA group vs 5.2% for Epi-GA group), there was a higher percent of postoperative pulmonary complications observed in the GA group (7.6%) compared to the Epi-GA group (2.6%). By facilitating early extubation and a decreased need for systemic narcotics in the early postoperative period, Epi-GA may be beneficial in the high risk pulmonary patient undergoing aortic reconstruction.


Multiple functions of mfa-1, a putative pheromone precursor gene of Neurospora crassa.
A putative pheromone precursor gene of Neurospora crassa, mfa-1 (which encodes mating factor a-1), was identified as the most abundant clone in starved mycelial and perithecial cDNA libraries. Northern analysis demonstrated high mfa-1 expression in all mating type a tissues and suggested low expression levels in mat A tissues. The mfa-1 gene was expressed as an approximately 1.2-kb transcript predicted to encode a 24-residue peptide, followed by a long 3' untranslated region (3' UTR). The predicted MFA1 sequence showed 100% sequence identity to PPG2 of Sordaria macrospora and structural similarity (a carboxy-terminal CAAX motif) to many hydrophobic fungal pheromone precursors. Mutants with a disrupted open reading frame (ORF) in which the critical cysteine residue had been changed to a nonprenylatable residue, tyrosine (YAAX mutants), were isolated, as were mfa-1 mutants with intact ORFs but multiple mutations in the 3' noncoding region (CAAX mutants). The 3' UTR is required for the full range of mfa-1 gene activity. Both classes of mutants showed delayed and reduced vegetative growth (which was suppressed by supplementation with a minute amount [30 micro M] of ornithine, citrulline, or arginine), as well as aberrant sexual development. When crossed as female parents to wild-type males, the CAAX and YAAX mutants showed greatly reduced ascospore production. No ascospores were produced in homozygous mfa-1 crosses. As males, YAAX mat a mutants were unable to attract wild-type mat A trichogynes (female-specific hyphae) or to initiate sexual development, while CAAX mat a mutants were able to mate and produce sexual progeny despite their inability to attract mat A trichogynes. In the mat A background, both CAAX and YAAX mutants showed normal male fertility but defective vegetative growth and aberrant female sexual development. Thus, the mfa-1 gene appears to have multiple roles in N. crassa development: (i) it encodes a hydrophobic pheromone with a putative farnesylated and carboxymethylated C-terminal cysteine residue, required by mat a to attract trichogynes of mat A; (ii) it is involved in female sexual development and ascospore production in both mating types; and (iii) it functions in vegetative growth of both mating types.


Whole-genome CRISPR screening identifies genetic manipulations to reduce immune rejection of stem cell-derived islets.
Human embryonic stem cells (hESCs) provide opportunities for cell replacement therapy of insulin-dependent diabetes. Therapeutic quantities of human stem cell-derived islets (SC-islets) can be produced by directed differentiation. However, preventing allo-rejection and recurring autoimmunity, without the use of encapsulation or systemic immunosuppressants, remains a challenge. An attractive approach is to transplant SC-islets, genetically modified to reduce the impact of immune rejection. To determine the underlying forces that drive immunogenicity of SC-islets in inflammatory environments, we performed single-cell RNA sequencing (scRNA-seq) and whole-genome CRISPR screen of SC-islets under immune interaction with allogeneic peripheral blood mononuclear cells (PBMCs). Data analysis points to "alarmed" populations of SC-islets that upregulate genes in the interferon (IFN) pathway. The CRISPR screen in vivo confirms that targeting IFNγ-induced mediators has beneficial effects on SC-islet survival under immune attack. Manipulating the IFN response by depleting chemokine ligand 10 (CXCL10) in SC-islet grafts confers improved survival against allo-rejection compared with wild-type grafts in humanized mice. These results offer insights into the nature of immune destruction of SC-islets during allogeneic responses and provide targets for gene editing.


Maximizing electron flux, microbial diversity and gene abundance in MFC powered electro-Fenton system by optimizing co-addition of lysozyme and 2-bromoethanesulfonate.
In this study, a microbial fuel cell powered electro-Fenton system (MFCⓅEFs) was established in order to overcome the shortcomings of low electron flux and unexpected methane production, while simultaneously treating excess sludge (ES, substrate) and refractory syringic acid (SA). A strategy of co-adding lysozyme (LZ, as ES degradation catalyst) and 2-bromoethanesulfonate (BES, as methane inhibitor) into ES was optimized in MFCⓅEFs to maximize electron flux, microbial community diversity and functional gene abundance. The removal of sludge total chemical oxygen demand (TCOD) achieved 81.69% in 25 d under an optimal co-addition strategy (40.41 mg/gSS of LZ, 27.03 mmol/L of BES, adding on 22.8 h of the7th day), with a simultaneous high degradation of SA (99.30% in 25 h). Correspondingly, a maximum power density of 3.35 W/m3 was achieved (only 0.62 W/m3 from the control), which effectively realizes in-situ micro-electricity generation and utilization for bioelectric Fenton processes. Moreover, 42.25% of the total charges were employed for bio-electricity generation. The electricigens of Pseudomonas, Acinetobacter and Chlorobium showed effective enrichment, while the abundance of methanogenesis archaea was extremely decreased. Functional genes associated with methanogenesis including mtaA, hdra, and mcrA were effectively inhibited. The life cycle assessment along with an optimized co-addition strategy illustrated a beneficial environmental effect, particularly in terms of ecosystem quality and climate change. Above all, an enhanced synchronous degradation of excess sludge and refractory pollutants had been realized in a green and environmentally friendly way.


Methodologies for Generating Brain Organoids to Model Viral Pathogenesis in the CNS.
(1) Background: The human brain is of interest in viral research because it is often the target of viruses. Neurological infections can result in consequences in the CNS, which can result in death or lifelong sequelae. Organoids modeling the CNS are notable because they are derived from stem cells that differentiate into specific brain cells such as neural progenitors, neurons, astrocytes, and glial cells. Numerous protocols have been developed for the generation of CNS organoids, and our goal was to describe the various CNS organoid models available for viral pathogenesis research to serve as a guide to determine which protocol might be appropriate based on research goal, timeframe, and budget. (2) Methods: Articles for this review were found in Pubmed, Scopus and EMBASE. The search terms used were "brain + organoid" and "CNS + organoid" (3) Results: There are two main methods for organoid generation, and the length of time for organoid generation varied from 28 days to over 2 months. The costs for generating a population of organoids ranged from USD 1000 to 5000. (4) Conclusions: There are numerous methods for generating organoids representing multiple regions of the brain, with several types of modifications for fine-tuning the model to a researcher's specifications. Organoid models of the CNS can serve as a platform for characterization and mechanistic studies that can reduce or eliminate the use of animals, especially for viruses that only cause disease in the human CNS.


Eosinophils: An imperative histopathological prognostic indicator for oral squamous cell carcinoma.
Inflammation in tumor microenvironment assists in both promotion and growth of tumor. Tumor-associated tissue eosinophilia (TATE) is the term used when eosinophils are observed in a tumor tissue with inflammatory infiltrate. Although carcinogenesis with inflammation is one of the important hallmarks, the exact role of eosinophils remains unclear. Various studies on oral squamous cell carcinoma (OSCC) that focused on eosinophils reported both favorable and unfavorable prognosis in cancer tissue, because of which the exact function of eosinophils still remains uncertain. The present study aims at identifying the role of TATE in OSCC and in malignant transformation of oral epithelial dysplasia (OED). The study includes 70 samples that divided into two groups, of which 50 histopathologically proven cases of different grades of OSCC and 20 cases of OED (oral leukoplakia). Congo red stain was used to stain the tissue sections. Each slide was viewed under high power in 10 consecutive microscopic fields for counting of eosinophils. Statistical analysis of values obtained was done using ANOVA, unpaired t-test and Mann-Whitney test. The results were statistically significant (P < 0.05) with a mean total eosinophil count of 2.12 in OED and 4.31 in OSCC. The present study showed higher eosinophil counts in OSCC when compared to dysplasia which should prompt for a thorough evaluation of tumor front for invasiveness. Therefore, tissue eosinophil count may be used as an adjunct to predict the malignant transformation of dysplastic lesions to OSCC.


Comparative analysis of prostatic acid phosphatase and prostate-specific antigen mRNA levels in hyperplastic prostate stimulated with steroid hormones and growth factors.
Prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) are the markers of human prostatic gland. However, it is still not completely understood if and how, steroid hormones and growth factors affect their expression and metabolism in the respect to the major pathologies of the gland. Appropriate studies were carried out on histopathologically diagnosed benign prostatic hyperplasia--BPH (n = 42) using tissue slices and cells derived from them. They were incubated with steroid hormones: 5-alpha-dihydrotestosterone (DHT), estradiol (E) and growth factors: epidermal growth factor (EGF), basic fibroblastic growth factor (bFGF) under culture conditions for up to 24 hours. P-labelled specific oligonucleotide probes were used to analyze total RNA isolated from each sample for the presence of PAP and PSA mRNAs. DHT, E, bFGF, EGF or both DHT + bFGF and DHT + EGF increased PAP and PSA mRNA levels in a time- and dose-dependent manner. The highest and statistically significant increase (P < 0.001) for PAP mRNA was observed when DHT + bFGF were present in the medium while for PSA mRNA if DHT + EGF were added to the medium. Slow but constant decrease of PAP and PSA mRNA levels was observed in the absence of each of these factors in the incubation medium. The results suggest that early expression of PSA and PAP genes and/or their mRNA stability strongly depend on DHT while differ in their response to EGF and bFGF.


The impact of new diagnostic methodologies in the management of meningitis in adults at a teaching hospital.
Suspected meningitis is a frequent reason for admission to hospital in the UK. While bacterial meningitis requires prompt antibiotic therapy to reduce mortality and morbidity, enteroviral meningitis, the most frequent viral cause, is almost invariably a benign disease. To determine the clinical presentation, laboratory findings and outcome of meningitis by microbiological aetiology and patient age, and to assess the clinical management of adults presenting with meningitis, with reference to national guidelines. Retrospective case-note review. Adult (>14 years) admissions to Addenbrooke's Hospital with meningitis or meningococcal septicaemia March 1996-September 2001 were audited retrospectively. The case definition was: symptoms compatible with meningitis, and either abnormal CSF (leukocytes >5x10(9)/ml) or meningococcal disease. The only exclusion criterion was the presence of a ventricular shunt. Only 30% of patients seen by a General Practitioner were given pre-admission antibiotics. In a substantial number of cases, including those with bacterial meningitis, antibiotic administration was delayed either because patients were sent for CT head scans (delaying a lumbar puncture) or because the diagnosis was not considered, especially in elderly patients with reduced conscious levels. There were no confirmed cases of H. influenzae meningitis. Overall outcomes in terms of mortality and disability were similar to UK national data. A surprising number of patients (40%) were afebrile on admission. The proportion of patients with meningitis given pre-hospital antibiotics by GPs is still worryingly low, although early hospital management has improved. Improved diagnostic facilities, particularly viral PCR assays, reduce antibiotic usage and hospital stay, with considerable financial savings.


Developing patient-centered care competencies among prelicensure nursing students using simulation.
Health care improvement requires collaboration between academia and practice to bridge gaps in nurse education and achievement of quality outcomes. Quality and Safety Education for Nurses identified six domains, including patient-centered care, that should be addressed during prelicensure education. Simulation is a recommended strategy to teach safe clinical practice; however, cost, space, and faculty resources are barriers to its use. Computer-based social simulation is less resource intensive and effective in improving critical-thinking skills. A pilot study was conducted to compare required resources and student learning outcomes for traditional versus computer-based simulation. Fifty-three baccalaureate nursing students participated in the study; 34 completed the computer-based simulation and 31 completed the traditional simulation. Group patient-centered care competency scores improved similarly (p < 0.001), although fewer faculty hours were required to administer the computer-based intervention. Findings suggest computer-based simulation is an efficient and effective learning strategy to develop patient-centered care competencies.