Assessing the synergies and trade-offs of development projects in response to climate change in an urban region.
A synthesis of the complex relationships, including synergies and trade-offs, between urban development projects and climate change mitigation and adaptation objectives can ensure that all these relationships are taken into consideration. We used a systems approach and applied an impact matrix and chain effect analysis methods to projects in the highly urbanized Taipei metropolitan region to identify the influences and effects between urban development projects and climate change objectives. Three types of urban plans and projects were analyzed: flood control, transportation, and urban planning. The magnitudes of the influences and effects between these projects and plans were derived through interviews with experts familiar with Taipei's urban development. This pilot study found no synergy in the response to climate change mitigation and adaptation for the urban development projects analyzed. The current standalone policies and plans related to urbanization in Taipei have resulted in trade-offs for flood control and public transit projects because they contribute positively toward one climate objective but negatively impact another. A high-level policymaking mechanism that ensures coordination and collaboration between different sectors is needed to supervise sectoral policies. Prior to the approval and implementation of a plan, policymakers should request the assessment of synergies and trade-offs between plans and projects to ensure a synergistic effect to climate change issues. This study confirms that the strategy from individual sector in a metropolitan region will result in trade-off between climate change issues is a global problem. This paper also strengthens the concept that the assessment of synergy/trade-offs between policy and plans should be conducted using systemic approach.


Corrigendum: Three naturally-occurring psychedelics and their significance in the treatment of mental health disorders.
[This corrects the article DOI: 10.3389/fphar.2022.927984.].


Synthesis of poly(Pro-Hyp-Gly)(n) by direct poly-condensation of (Pro-Hyp-Gly)(n), where n=1, 5, and 10, and stability of the triple-helical structure.
Pro-Hyp-Gly is a characteristic amino acid sequence found in fibrous collagens, and (Pro-Hyp-Gly)(10), which has been widely used as a collagen-model peptide, forms a stable triple-helical structure. Here, we synthesized polypeptides consisting of the Pro-Hyp-Gly sequence by direct poly-condensation of (Pro-Hyp-Gly)(n), where n=1, 5, and 10, using 1-hydroxybenzotriazole and 1-ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide hydrochloride in both phosphate buffer (pH=7.4) and dimethylsulfoxide (DMSO) solutions for 48 h at 20 degrees C. The reaction of (Pro-Hyp-Gly)(5) and (Pro-Hyp-Gly)(10) in DMSO successfully gave polypeptides with molecular weights over 10,000, whereas low molecular weight products were obtained by reaction in phosphate buffer (pH=7.4). In contrast, Pro-Hyp-Gly at a concentration of 50 mg/mL in phosphate buffer (pH=7.4) gave polypeptides with molecular weights over 10,000. The Fourier transform infrared (FTIR) and (1)H nuclear magnetic resonance (NMR) spectra of poly(Pro-Hyp-Gly)(10) revealed that the polymerization of (Pro-Hyp-Gly)(10) described in this report had no side reactions. Each polypeptide obtained shows a collagen-like triple-helical structure, and the triple-helical structures of poly(Pro-Hyp-Gly) and poly(Pro-Hyp-Gly)(10) were stable up to T=80 degrees C, which suggests that the high molecular weight promotes stability of the triple-helical structure, in addition to the high Hyp content. Furthermore, transmission electron microscopy (TEM) observations show that poly(Pro-Hyp-Gly)(10) aggregates to form nanofiber-like structures about 10 nm in width, which suggests that a Pro-Hyp-Gly repeating sequence contains enough information for triple-helix formation, and for subsequent nanofiber-like structure formation.


The Caenorhabditis elegans gene unc-76 and its human homologs define a new gene family involved in axonal outgrowth and fasciculation.
The gene unc-76 (unc, uncoordinated) is necessary for normal axonal bundling and elongation within axon bundles in the nematode Caenorhabditis elegans. The UNC-76 protein and two human homologs identified as expressed sequence tags are not similar to previously characterized proteins and thus represent a new protein family. At least one of these human homologs can function in C. elegans, suggesting that it, like UNC-76, acts in axonal outgrowth. We propose that the UNC-76 protein, which is found in cell bodies and processes of all neurons throughout development, either has a structural role in the formation and maintenance of axonal bundles or transduces signals to the intracellular machinery that regulates axonal extension and adhesion.


Centromeres, CENP-B and Tigger too.
The highly conserved centromere-associated protein CENP-B is a common feature of mammalian centromeres. Binding sites for CENP-B, so-called 'CENP-B boxes', are present in the otherwise unrelated centromeric satellite DNAs of humans, Mus musculus, Mus caroli, ferrets, giant pandas, tree shrews and gerbils, suggesting a role for CENP-B in centromere function. However, CENP-B and its binding sites are not detected at the centromeres of mammalian Y chromosomes and few, if any, binding sites seem present on African green monkey chromosomes. There is extensive sequence similarity between CENP-B and transposase proteins encoded by the pogo superfamily of transposable elements, which includes the human Tigger elements. Intriguingly, Tigger 2 has an almost perfect match to the CENP-B-binding site within its terminal inverted repeat. Comparison of the amino acid sequence of CENP-B with related proteins raises the possibility that CENP-B might share the ability to cause single-stranded DNA breaks. Such nicks could promote recombination, as has been suggested for the Charcot-Marie-Tooth disease duplication where a recombination hotspot exists close to a mariner-like element. We suggest that by promoting nicks adjacent to CENP-B boxes, CENP-B might facilitate the evolution and maintenance of satellite sequence arrays, rather than have a direct role in centromere function.


Lee-Goldburg solid-state imaging.
A new approach to solid-state imaging (SSI) is presented. The method relies on narrowing the resonance line using the Lee-Goldburg sequence. The technique is easy to implement in practice and may find widespread applications in materials science.


Computational study of the 1,3-dipolar cycloaddition between methyl 2-trifluorobutynoate and substituted azides in terms of reactivity indices and activation parameters.
The 1,3-dipolar cycloaddition of methyl 2-trifluorobutynoate with various azides has been studied in terms of several theoretical approaches at DFT/B3LYP/6-311++G(d,p) level of theory. The mechanism of regioselectivity of these reactions was investigated through the evaluation of the potential energy surface of the cycloaddition process calculations and density DFT-based reactivity indices. These approaches were successfully applied to prediction of preferable regio-isomers for various reactions of 1,3-dipolar cycloadditions. The reactions were followed by performing transition state optimization, calculation of Intrinsic Reaction Coordinate and activation energies. Analysis of the geometries of the corresponding transition structures shows that the cycloaddition takes place along a single elementary step (one-step mechanism) but asynchronous mechanism. The calculation of the activation energies and reaction energies show that the 1,5-regioisomer for substituted phenyl azides as dipoles and the 1,4-regioisomer for substituted benzyl azides as dipoles are thermodynamically in all the cycloadditions reactions. The solvent effect was also studied in the solvent tert-butyl alcohol using self-consistent reaction field model. The observed regioselectivity was explained by using developed DFT-based reactivity descriptors, such as Fukui and Parr functions. The results were compared with experimental data to find a good agreement.


Ultrastructure of the skin in mucopolysaccharidoses. Studies performed before and after plasma infusion therapy.
Skin biopsy specimens of two siblings with Hunter syndrome and two siblings with type B Sanfilippo syndrome were examined by electron microscopy, at six-month intervals, before and after plasma infusion therapy. Electron-lucent, membrane-bound vacuoles were seen in fibroblasts, Schwann cells, and in mononuclear cells both before and after the infusions. Based on the ultrastructural, clinical, and biochemical findings, it was concluded that there was no therapeutic benefit from these plasma infusions.


The Correlation Between Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio with Hepatic Echinococcosis.
To explore the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with hepatic hydatid diseases. The clinical data of 420 patients with hydatid disease who were treated in our hospital from October 2015 to October 2018 were collected from the database of our hospital. According to the postoperative pathological diagnosis, 200 patients were assigned into the alveolar echinococcosis (AE) group, and 220 patients were assigned into the cystic echinococcosis (CE) group. A total of 160 healthy examinees were enrolled as the control group. The main observation indexes included preoperative PLR and NLR. Pearson's correlation was used to analyze the correlation between PLR and NLR with clinical indicators in HE patients, and the receiver operator characteristic (ROC) curve was used to evaluate the clinical values of PLR and NLR in diagnosing different types of hydatid diseases. The results revealed that the expressions of PLR and NLR were significantly higher in the AE group than in the CE and control groups (P<0.05). The results of multiple linear regression analysis revealed that PLR was positively correlated with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase (P<0.05). NLR was correlated with albumin content (P<0.05). ROC curve analysis results revealed that the area under the curve (AUC) of PLR and NLR for AE was 0.800 and 0.700 respectively, and the AUC for CE was 0.78 and 0.75 respectively. The NLR and PLR of AE patients were higher than those of CE patients, and the high inflammation of CE patients may be correlated to the reproductive mode of Echinococcus multilocularis. PLR and NLR have certain diagnostic values for disease classification, but PLR has higher specificity when compared with NLR.


Ovarian stimulated cycles reduce protection of follicular fluid against free radicals.
Controlled ovarian hyperstimulation cycle with exogenous gonadotropins (COH) is associated with clinical complications. The aim of this work was to determine whether COH alters the physiological antioxidant status of follicular fluid in women with no reproductive dysfunction, compared to the natural cycle (NC). In this longitudinal study, forty-one women (oocyte donors) consecutively underwent NC and COH. Follicular fluid was collected at oocyte retrieval and different redox biomarkers were determined: total antioxidant activity (TAA), oxygen radical absorbance capacity (ORAC), nitric oxide, α- and γ-tocopherol, the fatty acid composition, activities of superoxide dismutase, catalase, total and Se-dependent glutathione peroxidases, and the antioxidant paraoxonase (PON) family. Results showed that TAA (1.70 ± 0.03 mM versus 1.86 ± 0.03 mM, p < 0.05), α-tocopherol (4.37 ± 0.26 μM versus 5.74 ± 0.30 μM, p < 0.05), PON1 paraoxonase (245 ± 24 nmol/min/ml versus 272 ± 27 nmol/min/ml, p < 0.05), PON1 arylesterase (87.2 ± 4.6 μmol/min/ml versus 99.3 ± 4.8 μmol/min/ml, p < 0.05), and PON3 simvastatinase (13.48 ± 0.52 nmol/min/ml versus 16.29 ± 0.72 nmol/min/ml, p < 0.001) were significantly lower in COH versus NC. Fatty acids from COH were more saturated, increasing palmitate and decreasing the n-6 and total polyunsaturated fatty acids (PUFAs). Docosahexaenoic acid also increased (p < 0.05). Results suggest that COH could lead to premature ovarian aging and provide new insights into the possible prevention of the adverse effects of ovarian hyperstimulation by directing therapeutic applications to the maintenance of the redox balance and fatty acid status, with special attention to paraoxonase proteins and docosahexaenoic acid.


DYT6 Dystonia Mimicking Adolescent Idiopathic Scoliosis Successfully Treated by Pallidal Stimulation.
Dystonia type 6 (DYT6) is an autosomal dominant monogenic movement disorder that often involves craniocervical and laryngeal regions, but can in rare circumstance present as trunk dystonia or severe scoliosis. Deep brain stimulation of the globus pallidus internus (GPi-DBS) has yielded favorable results in the treatment of DYT6 patients. This report describes the case of a 14-year-old male adolescent with DYT6 dystonia and severe scoliosis who was successfully treated by GPi DBS. The diagnosis of DYT6 dystonia was made after excluding other etiologies and was confirmed by next-generation sequencing. The patient underwent bilateral GPi-DBS implantation surgery under general anesthesia. The patient's Burke-Fahn-Marsden Dystonia Rating Scale score was 24 before surgery and decreased to 13.5 at 3 months, 3 at 6 months, and 2 at 12 months after bilateral GPi-DBS, corresponding to a 91% improvement from baseline to 12 months post-surgery. The patient's scoliosis improved significantly within 6 months after DBS. No complications occurred during surgery. An adolescent DYT6 patient with dystonia-related severe scoliosis was treated by bilateral GPi-DBS. The patient had an excellent outcome at 12 months after surgery, which prevented him from developing severe spinal deformity and disability. Early diagnosis of dystonia in adolescent patients can lead to timely and effective treatment. The etiology of severe scoliosis in adolescents should be carefully evaluated and differential diagnosis including dystonia should be considered. GPi-DBS in patients with DYT6 dystonia can prevent deformity.


Suppression of MAPK/NF-kB and activation of Nrf2 signaling by Ajugarin-I in EAE model of multiple sclerosis.
Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamate-induced HT22 cells and hydrogen peroxide (H2 O2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling.


Effects of antibiotics stress on root development, seedling growth, antioxidant status and abscisic acid level in wheat (Triticum aestivum L.).
The veterinary antibiotics contamination in agroecosystems is a substantial problem globally. However, little is known about their toxicity to crops, especially in wheat. This study evaluated the phytotoxic effects of the two most representative antibiotics, namely oxytetracycline (OTC) and enrofloxacin (ENR), on seed germination, seedling growth, root elongation and antioxidant status in wheat, and investigated the response of abscisic acid (ABA) to antibiotic stress and its underlying mechanism. The results showed that OTC and ENR under the experimental concentrations (5, 10, 20, 40 and 80 mg·L-1) had no influence on seed germination of wheat. The reduced root length, fresh weight and surface area were observed when the concentrations of OTC and ENR were higher than 10 mg·L-1 and 5 mg·L-1, respectively. High concentrations (>40 mg·L-1) of antibiotics dramatically decreased the root length, fresh weight, root numbers and surface area as well as the number of stele cells and stele area. The activity of catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD), and malondialdehyde (MDA) content in shoots and roots were increased with the increasing OTC and ENR concentrations. High concentrations (>40 mg·L-1) of antibiotics improved ABA content and enhanced the transcription levels of genes related to ABA biosynthesis (TaNCED1 and TaNCED2) and metabolism (TaABA8'OH1-A and TaABA8'OH2-A) in shoots and roots of wheat seedlings. Wheat seedlings had relatively strong sensitivity to low concentration (5 mg·L-1) of ENR. These results suggest that OTC and ENR modulate root development and seedling growth by regulating ABA level and antioxidant defense system in wheat.


Boron: Its Role in Energy-Related Processes and Applications.
Boron's unique position in the Periodic Table, that is, at the apex of the line separating metals and nonmetals, makes it highly versatile in chemical reactions and applications. Contemporary demand for renewable and clean energy as well as energy-efficient products has seen boron playing key roles in energy-related research, such as 1) activating and synthesizing energy-rich small molecules, 2) storing chemical and electrical energy, and 3) converting electrical energy into light. These applications are fundamentally associated with boron's unique characteristics, such as its electron-deficiency and the availability of an unoccupied p orbital, which allow the formation of a myriad of compounds with a wide range of chemical and physical properties. For example, boron's ability to achieve a full octet of electrons with four covalent bonds and a negative charge has led to the synthesis of a wide variety of borate anions of high chemical and electrochemical stability-in particular, weakly coordinating anions. This Review summarizes recent advances in the study of boron compounds for energy-related processes and applications.


Cell-matrix patterns in the cutaneous lesion of chromomycosis.
Chromomycosis is a chronic fungal infection characterized by dermal fibrosis with persisting fungi in situ, generally leading to a verrucous skin lesion. The absence of good clinical results under specific treatment suggests irreversibility of the fibrotic lesion. Frozen and paraffin-embedded skin biopsies of eleven patients with chromomycosis due to Phialophora pedrosoi were studied by immunohistochemistry and electron microscopy. Distinct cell-matrix patterns were found in different tissue localizations: neutrophilic abscesses with oedema and necrotic keratinocytes in the epidermis; dense connective matrix around inflammatory infiltrates, mainly composed of macrophages and giant cells, and organized granuloma in the dermis. Active fibroblasts and mast cells were constantly observed. The inability of fibrotic tissue to be remodelled seems correlated to the nature and the organization of the matrix components but, the factors triggering the initial fibrogenic events remain to be characterized.


Comparative performance of disposable soft contact lenses.
A short-term clinical study was undertaken to compare and evaluate the fit and clinical behaviour of eight disposable hydrogel contact lenses. Thirty subjects were enrolled in a 1-day, randomised, double-masked study. The lenses compared were Vistakon Acuvue (8.80), Vistakon Surevue (8.80), Aspect Frequency-55, Bausch & Lomb Medalist (SeeQuence 2), Ciba Focus (8.90), Lunelle Rythmic, Pilkington Barnes Hind Precision-Wand Wesley Jessen Freshlook. Three of the eight designs, Acuvue (86.7%), Precision-UV (86.7%) and Frequency-55 (90%), achieved relatively high levels of fitting success. The Rythmic lenses achieved the lowest success rate (70%) showing significantly greater downward decentration than the other designs. Although all the lenses were designed to fit a wide variety of eyes, they exhibited widely varying fitting characteristics. Some were more successful than others. The study shows that it is necessary for practitioners to utilise a range of lens designs in order to fit satisfactorily the typical contact lens population.


Long-term evolution of idiopathic lamellar macular holes and macular pseudoholes.
To analyze the natural evolution of idiopathic lamellar macular holes (LMH) and macular pseudoholes (MPH) in the long term, based on optical coherence tomography (OCT) configuration and on best corrected visual acuity (BCVA) evolution. A prospective, longitudinal study. We prospectively analyzed 108 eyes (67 left eyes and 41 right eyes) of 99 patients (55 female and 44 male) whose eyes had been diagnosed as having an MPH or an LMH on OCT examination. The following variables were assessed: BCVA; lens status; and hole size (diameter, residual foveal thickness, and perifoveal thickness) at baseline and at final examination. The mean follow-up period was 31.07 ± 18.77 (12 to 84) months. The mean BCVA (logMAR) in the total group at baseline was 0.31 ± 0.25, and at final examination it was 0.22 ± 0.21 (p = 0.200). Moreover, we did not observe statistically significant differences regarding diameter, residual foveal thickness, or perifoveal thickness (p = 0.325). Most idiopathic LMH and MPH do not progress anatomically and do not contribute to a significant diminution in visual acuity during the follow-up period.


Dietary vitamin E (alpha-tocopherol acetate) and selenium supplementation from different sources: performance, ascites-related variables and antioxidant status in broilers reared at low and optimum temperatures.
1. This study compared the effect of dietary supplementation with organic or inorganic selenium (Se) sources plus control amounts or large amounts of vitamin E (alpha-tocopherol acetate) in broilers raised at control (20 to 24 degrees C) or low (14.5 to 16.8 degrees C) temperatures after 2 weeks of age. 2. The following dietary treatments were used from one day old. Diet 1, the control diet, comprised a commercial diet containing 0.15 mg/kg inorganic Se and 50 mg vitamin E/kg feed. Diet 2 was the same as diet 1, supplemented with 0.15 mg/kg inorganic Se. Diet 3 was the same as diet 2 but was supplemented with 200 mg/kg vitamin E. Diet 4 was the same as diet 1, but inorganic Se was replaced with 0.30 mg/kg organic Se. Diet 5 was the same as diet 4, supplemented with 200 mg/kg vitamin E. 3. Low temperature reduced the growth rate of broilers; however, at 6 weeks, there were no differences in the body weights of birds fed on organic Se supplemented diets housed at low or control temperature. The feed conversion ratio was significantly affected by low temperature but not by diet. The heterophil/lymphocyte ratio was higher in chicks after one week in the cold, indicating mild stress. Blood triiodothyronine levels were significantly higher in birds after 1 and 4 weeks in the cold but thyroxin was not affected. 4. Organic Se supplementation increased relative lung weight at the control temperature, which might lead to greater respiratory capacity. Relative spleen weight significantly decreased in broilers fed diets supplemented with inorganic Se under cold conditions, a possible indication of chronic oxidative stress. 5. At the low temperature, supplementation with organic Se alone, or with inorganic Se and vitamin E increased glutathione peroxidase (GSHPx) activity and glutathione (GSH) concentration in the liver of broilers, which may indicate increased activity of birds' antioxidant defence against suboptimal environments.


An aptamer-based signal-on and multiplexed sensing platform for one-spot simultaneous electronic detection of proteins and small molecules.
One-spot signal-on and simultaneous electronic detection of lysozyme and adenosine is achieved based on target-induced release of aptamers and back-filling hybridization of the resulting single stranded DNAs with redox-tags conjugated aptamers.


[Diagnosis and treatment of paroxysmal reciprocal atrioventricular tachycardia].
The differential diagnostic criteria of paroxysmal reciprocating atrioventricular tachycardias were evaluated on the basis of a study of two clinical cases. Noninvasive (transoesophageal) electrophysiological methods were used. Evaluation of the trigger mechanism of arrhythmia, its form in comparison with data of Holter monitoring and vegetative testing allows to institute adequate antiarrhythmic therapy.


Engineering designer transcription activator-like effector nucleases (TALENs) by REAL or REAL-Fast assembly.
Engineered transcription activator-like effector nucleases (TALENs) are broadly useful tools for performing targeted genome editing in a wide variety of organisms and cell types including plants, zebrafish, C. elegans, rat, human somatic cells, and human pluripotent stem cells. Here we describe detailed protocols for the serial, hierarchical assembly of TALENs that require neither PCR nor specialized multi-fragment ligations and that can be implemented by any laboratory. These restriction enzyme and ligation (REAL)-based protocols can be practiced using plasmid libraries and user-friendly, Web-based software that both identifies target sites in sequences of interest and generates printable graphical guides that facilitate assembly of TALENs. With the described platform of reagents, protocols, and software, researchers can easily engineer multiple TALENs within 2 weeks using standard cloning techniques.


Reduction of bone mass in women after bone marrow transplantation.
Osteoporosis is a common disease among patients undergoing transplantation. Its prevalence and complications have been well described in solid organ recipients, especially kidney, liver, and heart. However, studies in bone marrow transplantation (BMT) are scarce. Among the mechanisms invoked in the pathogenesis of BMT osteoporosis are the baseline disease, the use of immunosuppressive drugs and, more remarkably, secondary hypogonadism. We present a study of 27 women who underwent BMT, all of them suffering ovarian failure. We studied different biochemical markers of bone formation/resorption and also evaluated the presence of osteopenia/osteoporosis by dual energy X-ray absorptiometry (DXA) of the lumbar spine. Osteopenia was observed in nine patients (33%) and osteoporosis in another five (18%), according to the World Health Organization criteria. We also detected a subgroup showing elevation of several bone turnover biochemical markers, indicating high osseous remodeling. A remarkable increase in urine hydroxyproline/creatinine was detected in 95% of cases, although an explanation is lacking. We outline a reasonable therapeutic approach for osteoporosis in BMT emphasizing the need to monitor these patients after transplantation.


Studies on the effects of L-thyroxine, L-carnitine and an L-thyroxine-L-carnitine combination on dipalmitoyl phosphatidylcholine content and on phosphatidylcholine species composition in fetal rat lungs.
The aim of the present study was to examine the effects of maternal carnitine treatment combined with thyroxine, a hormone influencing both lung maturation and carnitine metabolism. Administration of a carnitine-thyroxine combination to pregnant rats resulted in a significant increase of DPPC content in fetal rat lungs to 8.8 +/- 1.8 mg/g dry weight (mean +/- SD), compared with the control group, the carnitine-treated group, and the thyroxine-treated group [5.4 +/- 1.8 (p less than 0.01), 5.6 +/- 1.5 (p less than 0.01), and 6.6 +/- 1.0 mg/g dry weight, respectively]. The portion of DPPC in the PC species increased significantly from 20.9 +/- 2.1% in the control group and to 27.2 +/- 3.5% (p less than 0.01) in the carnitine-thyroxine combination group. A significant (p less than 0.01) diminution of the palmitoyl-palmitoleyl PC (16:0/16:1-PC) portion in the PC species was found. Maternal carnitine administration resulted in an elevation of the carnitine levels in the fetal lungs to approximately twice those of the controls (p less than 0.01). The combined administration of carnitine and thyroxine resulted in no increase in the total carnitine content but in a significant (p less than 0.01) increase of the short chain acylcarnitine content. The present results demonstrate that carnitine potentiates the effects of thyroxine on DPPC content and support the concept of an interrelationship between carnitine and thyroxine metabolism.


A Systematized Review of Atypical Antipsychotics in Pregnant Women: Balancing Between Risks of Untreated Illness and Risks of Drug-Related Adverse Effects.
To summarize risks related to (1) illness and (2) second-generation antipsychotic (SGA) treatment in pregnant women and their offspring. Concerning illness-related risks, we focused on bipolar disorder and schizophrenia, psychiatric disorders for which SGAs are preferentially prescribed. PubMed, Ovid, Scopus, PsycINFO, and Cochrane Library were searched from the date of the first available article to October 2015 using the following key terms: pregnancy OR gestation OR bipolar disorder OR schizophrenia. We also included cross-references from identified articles. We included 49 English-language articles regarding illness-related and SGA-related risks in bipolar disorder and schizophrenia. First, searches were done for epidemiologic or experimental studies (from January 2000 to October 2015), then for systematic reviews and meta-analyses. Data were extracted independently, after removing duplicates and studies that were not relevant or not pertinent. Abrupt discontinuation of treatment-exposed mothers with bipolar disorder or schizophrenia led to a high risk of relapses during pregnancy. Both bipolar disorder and schizophrenia were linked to a slightly increased risk of obstetric complications for mothers (schizophrenia) and the newborn (bipolar disorder and schizophrenia), although data on drug exposure during pregnancy were not given in the majority of studies. Maternal morbidity (schizophrenia but not bipolar disorder) may be associated with the worst neonatal outcomes (stillbirth, neonatal or infant deaths, and intellectual disability). Untreated bipolar disorder and schizophrenia may be considered independent risk factors for congenital malformations, while SGAs were not associated with increased recurring defects in fetuses. Evidence regarding the potential effects of SGAs on child neurodevelopment remains reassuring. After taking into account the parents' will and after they provide informed consent, the most reasonable and less harmful choice for treating future mothers with bipolar disorder or schizophrenia appears to be maintaining them at the safest minimum dosage.


Arm training in standing also improves postural control in participants with chronic stroke.
To prove the concept that postural control will improve without specific balance control training during arm training in standing with individuals with chronic stroke. Nine participants (mean age 64±7) received training involving hand orthotic assisted grasp, reach and release in standing 1 h, 3×'s/week for 6 weeks. Training focused on task completion with no explicit instructions provided for postural alignment, weight shift or balance strategy. Testing consisted of quantified measures using NeuroCom™ Balance Master, Berg Balance Scale (BBS) and Activities-specific Balance Confidence Scale (ABC). Post training participants demonstrate increased (p<.05) composite stability scores for sensory organization testing (mean 71.55±12.7-75.55±11). Velocity and directional control of COP weight shift improved for all 9 subjects with 6/9 achieving 100% target acquisition. Directional control improved (p<.05) for medial/lateral movements for all speeds and composite score. Anterior/posterior rhythmic weight shifting increased significantly in COP velocity control at moderate and fast velocities and composite score. Increases in mean BBS (p<.01) from 41.33±10.1-46.88±8.03 exceeded the clinically important cutoff for the scale. Balance confidence improved with ABC mean scores 70.22±14.5-79.55±12.86 (p<.05). Seven participants demonstrated changes above the minimally important difference for this scale. Postural control improved following task oriented arm training in standing without explicit postural control goals, instruction or feedback challenging current training paradigms of isolated postural control training with conscious attention directed to center of pressure location and movement.


The directionality of RuvAB-mediated branch migration: in vitro studies with three-armed junctions.
The Escherichia coli RuvA and RuvB proteins promote the branch migration of 4-way (Holliday) junctions during genetic recombination. The active complex is a tripartite structure in which RuvA protein is bound to the crossover and is sandwiched between two hexameric rings of RuvB. Branch migration requires ATP hydrolysis and occurs as the DNA passes through each RuvB ring. In this work, we have investigated the mechanism by which RuvAB catalyses the branch migration of a three-armed (Y) junction. Using synthetic DNA structures, we observed the formation of DNA products, a partial duplex DNA molecule and a single-stranded oligonucleotide, indicative of a branch migration reaction that occurred with unique polarity. Analysis of the RuvAB-junction complex by DNase footprinting showed that RuvA bound asymmetrically to the junction and targeted a single hexameric RuvB ring to one arm of DNA. Branch migration of a three-armed junction occurs in a unidirectional manner that is determined by the assembly of a single RuvB ring onto one arm of the DNA. The asymmetry of the complex and observed directionality of branch migration indicate that strand passage occurs as the DNA is pulled into the RuvB ring structure, a reaction likely to be coupled with DNA unwinding.


Recent developments in bio-scaffold materials as delivery strategies for therapeutics for endometrium regeneration.
Intrauterine adhesions (IUAs) refer to the repair disorder after endometrial injury and may lead to uterine infertility, recurrent miscarriage, abnormal menstrual bleeding, and other obstetric complications. It is a pressing public health issue among women of childbearing age. Presently, there are limited clinical treatments for IUA, and there is no sufficient evidence that these treatment modalities can effectively promote regeneration after severe endometrial injury or improve pregnancy outcome. The inhibitory pathological micro-environment is the main factor hindering the repair of endometrial damaged tissues. To address this, tissue engineering and regenerative medicine have been achieving promising developments. Particularly, biomaterials have been used to load stem cells or therapeutic factors or construct an in situ delivery system as a treatment strategy for endometrial injury repair. This article comprehensively discusses the characteristics of various bio-scaffold materials and their application as stem cell or therapeutic factor delivery systems constructed for uterine tissue regeneration.


Clustering of multiple lifestyle behaviors among migrant, left-behind and local adolescents in China: a cross-sectional study.
Influence of migration on externalized behavioral problems (e.g., aggressive) among adolescents has been well assessed, yet lifestyle behaviors of migrant, left-behind and local adolescents have been largely overlooked by researchers and policy-makers. Therefore, this study aimed to identify clustering of multiple lifestyle behaviors and their associations with migrant status among Chinese adolescents. A cross-sectional survey was conducted in 2015 in Beijing, and Wuhu city (Anhui province). Adolescents self-reported age, gender, family economic status, migrant situation, and lifestyle behaviors (i.e., physical activity, screen time, sleep, smoke, soft-drink, alcohol, fruit and vegetable consumption) via a battery of validated questionnaires. Latent class analysis was conducted to identify behavioral clusters using Mplus 7.1. ANOVA, and multivariable logistic regression were used to examine associations between migrant situations and behavioral clusters using SPSS 22. Three distinct behavioral clusters were exhibited among 1364 students (mean age: 13.41 ± 0.84 years): "low risk" (N = 847), "moderate risk" (N = 412) and "high risk" (N = 105). The "high-risk" cluster had the highest prevalence of adolescents not meeting healthy behavioral recommendations. There were no significant differences in the prevalence of high-risk lifestyle among migrant, left-behind, rural local and urban local adolescents. But migrant adolescents had the lowest prevalence of low-risk lifestyle, followed by left-behind, rural and urban local adolescents. Moreover, compared with urban local, migrant (OR = 2.72, 95%CI: 1.88,3.94), left-behind (OR = 2.28, 95%CI: 1.46, 3.55), and rural local (OR = 1.76, 95%CI:1.03,3.01) adolescents had a higher risk of moderate-risk lifestyle. Clustering of assessed lifestyle behaviors differed by the migrant status. Particularly, migrant and left-behind adolescents were more likely to have moderate-risk lifestyle compared with their counterparts. Interventions that promote moderate to vigorous physical activity and consumption of fruits and vegetables simultaneously are needed among them.


Development of college student focused care in a psychiatric hospital: Preliminary clinical outcomes and future directions.
The unique features of college experience make it essential to address escalating mental-health challenges beyond college campuses. In 2010, we launched college-student focused (CSF) care nested within an adult day treatment program in a psychiatric hospital. The CSF care consists of student group therapies, individual consultation services for hospital staff and student-patients, and student-focused mental health guides for patients and families. This study preliminarily examined the clinical impact of CSF care on post-treatment symptoms reduction. In 235 college student-patients admitted to the day program between 2011 July to 2013 January, we assessed the targeted outcomes of the CSF care, using a newly developed CSF questionnaire. Higher levels of CSF care-related outcomes predicted reduced post-treatment depression and anxiety, even after controlling for baseline clinical symptoms and post-treatment skills usage. These results highlighted the benefits and need for CSF care on a healthcare system level.


Sorafenib in renal cell carcinoma.
Metastatic renal cell carcinoma is resistant to conventional treatment with chemotherapy. Recently the use of molecular-targeted therapies with multikinase inhibitors has been recommended as first-choice therapy because they inhibit cell proliferation and tumour angiogenesis. Sorafenib is a well tolerated tyrosine kinase inhibitor that initially demonstrated efficacy in the treatment of patients with metastatic RCC who progressed after immunotherapy. Expanded-access studies in Europe and North America showed the safety and efficacy of sorafenib in special populations such as elderly, renal failure and cerebral metastases, as well as patients with no prior therapy. No cross-resistance has been suggested in non-randomized trials when used in second line treatment after other targeted therapies. Ongoing clinical trials will better define the role of sorafenib in first and second line either as monotherapy or in combination, as well as the best strategies for the sequential use of this drug.


The underlying mechanism of intersite discrepancies in ejection time measurements from arterial waveforms and its validation in the Framingham Heart Study.
Radial applanation tonometry is a well-established method for clinical hemodynamic assessment and is also becoming popular in wrist-worn fitness trackers. The time difference between the foot and the dicrotic notch of the arterial pressure waveform is a well-accepted approximation for the left ventricular ejection time (ET). However, several clinical studies have shown that ET measured from the radial pressure waveform deviates from that measured centrally. In this work, we consider the systolic wave and the dicrotic wave as two independent traveling waves and hypothesize that their wave speed difference leads to the intersite differences of measured ET (ΔET). Accordingly, we derived a mathematical dicrotic wave decomposition model and identified the most influential factors on ΔET via global sensitivity analysis. In our clinical validation on a heterogeneous cohort (N = 5,742) from the Framingham Heart Study (FHS), the local sensitivity analysis results resembled the sensitivity variation patterns of ΔET from model simulations. A regression analysis on FHS data, using morphological features of radial pressure waveforms to estimate the carotid ET, produced a root mean square error of 3.76 ms and R2 of 0.91. The proposed dicrotic wave decomposition model can explain the intersite ET measurement discrepancies observed in the clinical data of FHS and can facilitate the precise identification of ET with radial pressure waveforms. Therefore, the proposed model will improve various physics-based pulse wave analysis methods as well as prospective artificial intelligence methods for tackling the subsequent big data produced from widespread wearable radial pressure monitoring.NEW & NOTEWORTHY Based on a new understanding of pressure wave propagation, we propose a novel dicrotic wave decomposition model considering the dicrotic wave as an independent traveling component. The proposed model can explain the mechanism underlying the intersite discrepancies in ejection time measurement from arterial waveforms and then, in principle, enhance the accuracy of both classical physics-based as well as more contemporary artificial intelligence-based pulse wave analysis methods in clinical and wearable radial blood pressure monitoring applications.


The metabolic homeostaTOR: The balance of holding on or letting grow.
Plants, as autotrophic organisms, capture light energy to convert carbon dioxide into ATP, NADPH, and sugars, which are essential for the biosynthesis of building blocks, cell proliferation, biomass accumulation, and reproductive fitness. The Target Of Rapamycin (TOR) signalling pathway is a master regulator in sensing energy and nutrients, adapting the metabolic network and cell behaviour in response to environmental resource availability. In the past years, exciting advances in this endeavour have pointed out this pathway's importance in controlling metabolic homeostasis in various biological processes and systems. In this review, we discuss these recent discoveries highlighting the need for a metabolic threshold for the proper function of this kinase complex at the cellular level and across distinct tissues and organs to control growth and development in plants.


Correlation between intraocular pressure reduction and anterior chamber aqueous flare after micropulse transscleral cyclophotocoagulation.
Micropulse transscleral cyclophotocoagulation (MP-CPC) is a technique that has been approved in recent years to treat glaucoma. MP-CPC causes anterior chamber inflammation; a relationship with reduced intraocular pressure (IOP) has not been reported. Therefore, we analyzed the correlation between IOP and anterior chamber aqueous flare after MP-CPC. This retrospective study included 37 eyes of 37 patients who underwent MP-CPC between November 2018 and October 2020. IOP and flare values were measured at 1, 4, and 12 weeks after MP-CPC. Correlations were assessed between the percentage IOP reduction and flare elevation by calculating Spearman's rank correlation coefficient. The percentage IOP reduction at 1 week after surgery was correlated with the flare elevation at 1 week after surgery (ρ = 0.47, P = 0.006). The percentage IOP reduction at 12 weeks after surgery was correlated with the flare elevation at 4 weeks after surgery (ρ = 0.53, P = 0.006). A short-term correlation was implied between reduced IOP and flare elevation after MP-CPC.


Lessons Learned From a Peer Writing Coach Program in a School of Public Health.
Clear writing is a critical component of public health research and practice. The ability to convey information in a concise, engaging, and insightful manner influences stakeholder engagement and is the backbone of program and policy development, organization, and implementation. To help master of public health (MPH) students adapt their writing skills to these specialized demands, Boston University School of Public Health launched the Peer Writing Coach Program in 2010 staffed by MPH students. The service is open to all students enrolled in public health classes. They can schedule up to 2 appointments per assignment for both individual and team papers. Student use increased from 55 appointments in academic year 2010-2011 (the first year of the program) to 767 appointments in academic year 2017-2018. For the 2016-2017, 2017-2018, and 2018-2019 academic years, 1128 (74%) of 1530 appointment requests asked for assistance "writing clearly and concisely," 886 (58%) for assistance "organizing and synthesizing main points of argument," and 529 (35%) for assistance "tailoring writing for a specific audience." This case study describes the rationale for creating the program, outlines the chronology of its development since 2010, and provides an overview of peer coach training, student use, and lessons learned as we addressed logistical challenges.


A research education program model to prepare a highly qualified workforce in biomedical and health-related research and increase diversity.
The National Institutes of Health has recognized a compelling need to train highly qualified individuals and promote diversity in the biomedical/clinical sciences research workforce. In response, we have developed a research-training program known as REPID (Research Education Program to Increase Diversity among Health Researchers) to prepare students/learners to pursue research careers in these fields and address the lack of diversity and health disparities. By inclusion of students/learners from minority and diverse backgrounds, the REPID program aims to provide a research training and enrichment experience through team mentoring to inspire students/learners to pursue research careers in biomedical and health-related fields. Students/learners are recruited from the University campus from a diverse population of undergraduates, graduates, health professionals, and lifelong learners. Our recruits first enroll into an innovative on-line introductory course in Basics and Methods in Biomedical Research that uses a laboratory Tool-Kit (a lab in a box called the My Dr. ET Lab Tool-Kit) to receive the standard basics of research education, e.g., research skills, and lab techniques. The students/learners will also learn about the responsible conduct of research, research concept/design, data recording/analysis, and scientific writing/presentation. The course is followed by a 12-week hands-on research experience during the summer. The students/learners also attend workshops and seminars/conferences. The students/learners receive scholarship to cover stipends, research related expenses, and to attend a scientific conference. The scholarship allows the students/learners to gain knowledge and seize opportunities in biomedical and health-related careers. This is an ongoing program, and during the first three years of the program, fifty-one (51) students/learners have been recruited. Thirty-six (36) have completed their research training, and eighty percent (80%) of them have continued their research experiences beyond the program. The combination of carefully providing standard basics of research education and mentorship has been successful and instrumental for training these students/learners and their success in finding biomedical/health-related jobs and/or pursuing graduate/medical studies. All experiences have been positive and highly promoted. This approach has the potential to train a highly qualified workforce, change lives, enhance biomedical research, and by extension, improve national health-care.


A Characterization of Maximally Entangled Two-Qubit States.
As already known by Rana's result, all eigenvalues of any partial-transposed bipartite state fall within the closed interval [-12,1]. In this note, we study a family of bipartite quantum states where the minimal eigenvalues of partial-transposed states are -12. For a two-qubit system, we find that the minimal eigenvalue of its partial-transposed state is -12 if and only if such a two-qubit state is maximally entangled. However this result does not hold in general for a two-qudit system when the dimensions of the underlying space are larger than two.


A Phase I trial: dose escalation of melphalan in the "BEAM" regimen using amifostine cytoprotection.
With the eventual goal of reducing relapse and thus improving overall survival in selected lymphoma patients, a Phase I study was performed using the cytoprotectant amifostine to permit safe dose-augmentation of melphalan in the carmustine (BCNU), etoposide, cytarabine (arabinosylcytosine), and melphalan (BEAM) regimen before autologous hematopoietic stem cell transplantation. Between 30 July 2003 and 25 November 2008, a total of 32 lymphoma patients were entered, of which 28 were evaluable. We found the melphalan dose in BEAM could be safely escalated to at least 260 mg/m², a substantial increase from the usual dose of 140 mg/m² in BEAM while the trial was terminated early due to poor accrual, no maximal tolerated dose or dose-limiting toxicity was found. A Phase II trial is planned.


Observation after surgery for low grade glioma: long-term outcome in the light of the 2016 WHO classification.
To provide detailed long-term data after initial observation for patients after histological confirmation of low grade (WHO II) gliomas according to molecular stratification. A series of 110 patients with watchful waiting strategy after initial surgery for LGG and re-surgery at tumor progression were analyzed. Progression-free survival, time to malignant transformation, post-recurrence survival, and overall survival were estimated with the Kaplan-Meier method. Prognostic factors were identified by the Log Rank test and Cox multivariate proportional hazards model. The cohort comprised 18 IDH wild type (IDHwt) and 53 IDH mutated (IDHmut) astrocytomas, and 39 IDH mutated and 1p 19q co-deleted (IDHmut/codel) patients. The median follow-up was 126 (95% CI 109-143) months. Surgery was gross total resection in 58, subtotal resection in 28, and biopsy in 24 patients. Progression-free survival rates at 5, 10 and 15 years was 38% 18% and 1%. The corresponding malignant transformation rates were 17%, 39% and 71%. The initial extent of resection influenced progression-free survival, time to malignant transformation and overall survival. Molecular subtype IDHmut/codel was the strongest prognostic factor for overall survival and for time to malignant transformation. The strongest determinant of the patients' course after initial watchful waiting was the molecular tumor status. Extensive resection may increase time to progression and malignant transformation. Observation may be justified in selected patients.


N-methyl-D-aspartate transmission modulates GABAB-mediated inhibition of rat hippocampal pyramidal neurons in vitro.
Slow inhibition was investigated by stimulating inhibitory neurons at the border of stratum radiatum and lacunosum-moleculare with focal microapplications of glutamate, while recording resultant slow inhibitory postsynaptic potentials in CA1 pyramidal neurons in rat hippocampal slices. The slow inhibitory postsynaptic potentials evoked had an average peak amplitude of -2.2 mV, measured at -60 mV. Their peak conductance was 2.5 nS. These events were characterized as slow GABAB inhibitory postsynaptic potentials because they reversed at -90 mV, and were blocked by CGP 35348 (500 microM). Exposure to magnesium-free solutions augmented glutamate-evoked slow inhibitory postsynaptic potentials. Mean peak amplitude and conductance were -3.1 mV and 4.0 nS. Exposure to the N-methyl-D-aspartate antagonist MK-801 (20 microM) allowed separation of the glutamate-triggered slow inhibitory postsynaptic potential into components induced by non-N-methyl-D-aspartate and N-methyl-D-aspartate receptor activation. The N-methyl-D-aspartate component dominated, even under control conditions, and could account for up to 60% of the control slow inhibitory postsynaptic potential. Thus, the activation and recruitment of GABAB-mediated inhibition depend on both non-N-methyl-D-aspartate and N-methyl-D-aspartate-mediated excitation of inhibitory interneurons. Under physiological conditions slow inhibition may act as an important synaptic filtering mechanism, but when N-methyl-D-aspartate-mediated excitation increases, slow inhibition is further recruited, providing an important means to offset excessive excitation.


Material and energy balances of an integrated biological hydrogen production and purification system and their implications for its potential to reduce greenhouse gas emissions.
The materials and energy in an integrated biological hydrogen production and purification system involving hydrolysis, dark fermentation, photo fermentation, CO2 fixation and anaerobic digestion are balanced by integrating the results from multiple experiments, simulations and the literature. The findings are two fold. First, using 1000 kg rice straw as a substrate, 19.8 kg H2 and 138.0 kg CH4 are obtained. The net energy balance (NEB) and net energy ratio (NER) are -738.4 kWh and 77.8%, respectively, both of which imply an unfavorable energy production system. Opportunities to improve the performance particularly lie in the photo fermentation process. Second, greenhouse gas emissions are evaluated for various options. The results were comparable with the emission inventory of electricity generated from fossil fuels. NEB and NER under a zero-carbon-emission constraint were discussed in detail to clarify completely the implications of the energy and material balances on greenhouse gas emissions.


Short-term deep brain stimulation of the thalamic reticular nucleus modifies aberrant oscillatory activity in a neurodevelopment model of schizophrenia.
Dysfunction of thalamo-cortical networks involving particularly the thalamic reticular nucleus (TRN) is implicated in schizophrenia. In the neonatal ventral hippocampal lesion (NVHL), a heuristic animal model of schizophrenia, brain oscillation changes similar to those of schizophrenic patients have been reported. The aim of this study was to analyze the effects of short-term deep brain stimulation (DBS) in the thalamic reticular nucleus on electroencephalographic (EEG) activity in the NVHL. Male and female Sprague-Dawley rats were used and the model was prepared by excitotoxicity damage of the ventral hippocampus on postnatal day 7 (PD-7). Chronic bilateral stainless steel electrodes were implanted in the TRN, thalamic dorsomedial nucleus and prelimbic area at PD-90. Rats were classified as follows: sham and NVHL groups, both groups received bilateral DBS in the TRN for one hour (100Hz, 100µs pulses, 200µA). All animals showed a sudden behavioral arrest accompanied by widespread symmetric bilateral spike-wave discharges, this activity was affected by DBS-TRN. Additionally, the power spectra of 0.5-100Hz and the coherence of 0.5-4.5 and 35-55Hz frequencies were modified by DBS-TRN. Our results suggest that DBS in the TRN may modify functional connectivity between different parts of the thalamo-cortical network. Additionally, our findings may suggest a beneficial effect of DBS-TRN on some preclinical aberrant oscillatory activities in a neurodevelopmental model of schizophrenia.


Applying life cycle assessment to assess the environmental performance of decentralised versus centralised wastewater systems.
Decentralised wastewater management (DWM) systems are deployed in areas where the topography does not allow for gravity flow to a centralised system, or requires a complex and expensive pumping station network. Also, DWM systems are often the only option in rural areas where there are no sewage transport networks. This paper aims at addressing the question of the degree to which DWM systems can be considered as viable alternatives from an environmental point of view using the Life Cycle Assessment (LCA) methodology. First, the environmental sustainability is investigated to identify environmental hotspots in two (nature-based and engineered) onsite DWM systems. Second, DWM scenarios are compared against centralised wastewater management (CWM) scenarios using a whole-systems approach. Finally the boundary conditions under which a given DWM scenario performs better than a CWM scenario are discussed. Results show CWM scenarios were less sustainable than DWM scenarios on the resources endpoint due to their sewer infrastructures, however CWM scenarios performed better than DWM scenarios on the ecosystems quality endpoint due to their well-managed air emissions and discharges. While on human health no clear conclusion could be drawn. Finally, for relatively few households (subject of the study in rural areas) CWM scenarios did not score superior performances compared to DWM scenarios on all three endpoint indicators. Yet for a greater number of households it was impossible to decide in favour of decentralisation because of a lack of favourable consensus on all three endpoint indicators.


Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres.
The trilaminar kinetochore directs the segregation of chromosomes in mitosis and meiosis. Despite its importance, the molecular architecture of this structure remains poorly understood [1]. The best known component of the kinetochore plates is CENP-C, a protein that is required for kinetochore assembly [2], but whose molecular role in kinetochore structure and function is unknown. Here we have raised for the first time monospecific antisera to CENP-A [3], a 17 kD centromere-specific histone variant that is 62% identical to the carboxy-terminal domain of histone H3 [4,5] and that resembles the yeast centromeric component CSE4 [6]. We have found by simultaneous immunofluorescence with centromere antigens of known ultrastructural location that CENP-A is concentrated in the region of the inner kinetochore plate at active centromeres. Because CENP-A was previously shown to co-purify with nucleosomes [7], our data suggest a specific nucleosomal substructure for the kinetochore. In human cells, these kinetochore-specific nucleosomes are enriched in alpha-satellite DNA [8]. However, the association of CENP-A with neocentromeres lacking detectable alpha-satellite DNA, and the lack of CENP-A association with alpha-satellite-rich inactive centromeres of dicentric chromosomes together suggest that CENP-A association with kinetochores is unlikely to be determined solely by DNA sequence recognition. We speculate that CENP-A binding could be a consequence of epigenetic tagging of mammalian centromeres.


Molecularly imprinted polymers for sensing gaseous volatile organic compounds: opportunities and challenges.
Chemical sensors that can detect volatile organic compounds (VOCs) are the subject of extensive research efforts. Among various sensing technologies, molecularly imprinted polymers (MIPs) are regarded as a highly promising option for their detection with many advantageous properties, e.g., specific binding-site for template molecules, high recognition specificity, ease of preparation, and chemical stability. This review covers recent advances in the sensing application of MIPs toward various types of VOCs (e.g., aliphatic and aromatic compounds). Particular emphasis has been placed on multiple approaches to the synthesis of MIP-based VOC sensors in association with their performance and sensing mechanisms. Current challenges and opportunities for new VOC-sensing applications are also discussed based on MIP technology.


Effects of lifestyle intervention in obese pregnant women on gestational weight gain and mental health: a randomized controlled trial.
Lifestyle intervention could help obese pregnant women to limit their weight gain during pregnancy and improve their psychological comfort, but has not yet been evaluated in randomized controlled trials. We evaluated whether a targeted antenatal lifestyle intervention programme for obese pregnant women influences gestational weight gain (GWG) and levels of anxiety or depressed mood. This study used a longitudinal interventional design. Of the 235 eligible obese pregnant women, 205 (mean age (years): 29±4.5; body mass index (BMI, kg m(-)(2)): 34.7±4.6) were randomized to a control group, a brochure group receiving written information on healthy lifestyle and an experimental group receiving an additional four antenatal lifestyle intervention sessions by a midwife trained in motivational lifestyle intervention. Anxiety (State and Trait Anxiety Inventory) and feelings of depression (Edinburgh Depression Scale) were measured during the first, second and third trimesters of pregnancy. Socio-demographical, behavioural, psychological and medical variables were used for controlling and correcting outcome variables. We found a significant reduction of GWG in the brochure (9.5 kg) and lifestyle intervention (10.6 kg) group compared with normal care group (13.5 kg) (P=0.007). Furthermore, levels of anxiety significantly decreased in the lifestyle intervention group and increased in the normal care group during pregnancy (P=0.02); no differences were demonstrated in the brochure group. Pre-pregnancy BMI was positively related to levels of anxiety. Obese pregnant women who stopped smoking recently showed a significant higher GWG (β=3.04; P=0.01); those with concurrent gestational diabetes mellitus (GDM) (β=3.54; P=0.03) and those who consumed alcohol on a regular base (β=3.69; P=0.04) showed significant higher levels of state anxiety. No differences in depressed mood or obstetrical/neonatal outcomes were observed between the three groups. A targeted lifestyle intervention programme based on the principles of motivational interviewing reduces GWG and levels of anxiety in obese pregnant women.


Integration of quantitative proteomics and metabolomics reveals tissue hypoxia mechanisms in an ischemic-hypoxic rat model.
Tissues hypoxia caused by hemorrhage is a common complication in many clinical diseases. However, its pathological mechanism remains largely unknown. To partly address this issue, an ischemic-hypoxic rat model was established and the plasma proteomic and metabolic profiles were quantified and analyzed using TMT-based quantitative proteomics and metabolomics. The analysis revealed a total of 177 differentially expressed proteins and 32 metabolites that were uniquely altered in the hypoxic rat plasma, compared to the control. Bioinformatics analysis showed that these altered proteins and metabolites were involved in a wide range of biological processes. Twelve of the 177 differentially expressed proteins were involved in PI3K-Akt signaling, a pathway that has been reported to be strongly associated with tissue hypoxia. Other signaling pathways such as complement and coagulation cascades, GnRH signaling, relaxin signaling, protein processing in endoplasmic reticulum, as well as AGE-RAGE signaling were markedly altered in the ischemic-hypoxic response, implying their potential roles in tissue hypoxia. A joint analysis of proteome and metabolome showed that the significantly altered metabolites such as guanine, tryptamine, dopamine, hexadecenoic, l-methionine, and fumarate may have participated in the pathogenesis of tissue hypoxia. Further, we found that changes in the levels of metabolites matched the changes in protein abundance within the same pathway. Overall, this study presents an overview of the molecular networks in ischemic-hypoxic pathology and offers biochemical basis for further study on the mechanism of tissue hypoxia. SIGNIFICANCE: We employed an integrated metabonomic-proteomic method to systematically analyze the profiles of metabolites and proteins in an ischemic-hypoxic rat model. Bioinformatics and enrichment analysis showed that the differentially expressed proteins were mainly involved in complement and coagulation cascades, PI3K-Akt signaling, GnRH signaling, relaxin signaling, protein processing in endoplasmic reticulum, and AGE-RAGE signaling. Moreover, a panel of 12 candidate proteins involved in PI3K-Akt signaling (i.e., Vtn, Hsp90b1, Ywhae, Tnc, Ywhaz, Thbs4, Lamc1, Col1a1, Il2rg, Egfr, Newgene 621,351, and Tfrc) may serve as the potential biomarkers to predict tissue hypoxia.


Temporally independent association of multiple evanescent white dot syndrome and optic neuritis.
To describe three patients that developed temporally distinct episodes of optic neuritis and multiple evanescent white dot syndrome (MEWDS). We retrospectively reviewed the medical records and imaging studies of three women evaluated at a tertiary referral center for both optic neuritis and MEWDS. Three otherwise healthy women, aged 17, 36, and 41, developed temporally separated episodes of optic neuritis and MEWDS. The time periods between the two events were 3, 48, and 60 months, and in two of the three cases, the optic neuritis event preceded the episode of MEWDS. No patient endorsed prodromal flu-like symptoms prior to developing vision loss. The mean presenting visual acuities were better with the optic neuritis episode (LogMAR 0.360, Snellen 20/46) than with retinal event (LogMAR 0.684, Snellen 20/97). All three patients had improvement in vision, with mean visual acuity of 20/29 (LogMAR 0.165) at last follow-up. One patient later developed idiopathic noninfectious posterior uveitis and another developed multiple sclerosis requiring treatment. While a rare association, patients can develop both optic neuritis and MEWDS within the same eye at different time points. It is unknown whether such patients are at even higher risk of developing systemic autoimmune disease than are patients with either MEWDS or optic neuritis alone.


An overview of Notch3 function in vascular smooth muscle cells.
Proteins of the Notch family are cell surface receptors that transduce signals between neighbouring cells. The Notch signalling pathway is highly evolutionarily conserved and critical for cell fate determination during embryonic development, including many aspects of vascular development. The interaction of Notch receptors with ligands leads to cleavage of the Notch intracellular domain (NICD) which then translocates to the nucleus and activates the transcription factor CBF1/JBP-Jkappa, regulating downstream gene expression. To date four Notch receptors have been found in mammals. Of these, Notch3 is predominantly expressed in adult arterial smooth muscle cells in human. NOTCH3 gene mutations cause the autosomal dominant condition, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoecephelopathy (CADASIL), an inherited early stroke syndrome leading to dementia due to systemic vascular degeneration. This suggests that Notch3 plays a critical role in maintaining the phenotypic stability of vascular smooth muscle cells (VSMCs). Recent publications indicate that Notch3 is involved in vascular injury and is a determinant of VSMC survival, but its exact function is unknown. The molecular mechanisms underlying CADASIL pathology are therefore intriguing. Investigation of CADASIL mutant Notch3 shows that the majority of mutations do not change CBF1/JBP-Jkappa mediated classic Notch activation, so the pathological consequences of NOTCH3 mutations in CADASIL patients can not be simply explained by loss- or gain-of-function in the classic Notch signalling pathway. This suggests that a novel Notch3-mediated signalling pathway may be present in VSMCs, or cross-regulation of Notch3 to other signalling pathway(s) may play a critical role on VSMCs survival. Alternatively, the mutant Notch3 may gain a novel or toxic function in VSMCs. This review will focus on recent findings of Notch3 in vascular development and in regulating the VSMC behaviour and phenotype, and will use findings on investigating the molecular pathology of the single gene disorder CADASIL to understand the function of Notch3 in VSMCs.


Association of prenatal sex steroid exposure estimated by the digit ratio (2D:4D) with birth weight, BMI and muscle strength in 6- to 13-year-old Polish children.
The aim of this paper was to provide evidence for the impact of prenatal sex steroid exposure on prenatal and postnatal body size parameters, and muscle strength in children. The following anthropometric data were studied in a group of 1148 children (536 boys and 612 girls) aged 6-13 years: the 2D:4D digit ratio, birth weight and length, and birth head and chest circumference. Postnatal parameters (6-13 years) included body weight and height, BMI, waist and hip circumference, WHR, as well as grip strength in both hands. All parameters that required it were adjusted for sex and gestational or chronological age. A general linear model, Pearson's correlation, t-statistics and Cohen's Δ were used in statistical analysis. Among birth size parameters, only birth weight was significantly negatively correlated with the 2D:4D digit ratio in children. Higher (feminized) digit ratios were significantly correlated with postnatal parameters such as body weight, BMI, and waist and hip circumference (positively), as well as hand grip strength-a proxy for muscular strength (negatively). Problems with maintaining adequate body size parameters and muscle strength may be programmed in fetal life and predicted on the basis of the 2D:4D digit ratio. Body weight at birth and in early ontogenesis are additive correlates of the 2D:4D ratio. The present findings suggest that the 2D:4D digit ratio is related to postnatal phenotypes such as birth weight, overweight, and obesity as well as muscle strength in 6-13-year-old children of both sexes.


Filter lifespan, treatment effect, and influencing factors of continuous renal replacement therapy for severe burn patients.
Continuous renal replacement therapy (CRRT) is often disrupted due to various factors, such as patient-related issues, vascular access complications, treatment plans, and medical staff factors. This unexpected interruption is referred to as non-selective filter stoppage and can result in additional treatment expenses. This study retrospectively analyzed 501 CRRT filters used in 62 patients with severe burns, lifespan and therapeutic effect of all filters were mainly analyzed, used logistic regression analysis was performed to identify risk factors associated with non-selective cessation filter. Out of 493 filters, 279 cases received heparin (56.60%), the median lifespan of the filter was 14.08 hours (25th,75th quantile:7.30,21.50); 128 cases were treated with nafamostat mesylate (26.00%), and the median lifespan of the filter was 16.42 hours (10.49,22.76); 86 cases were treated with sodium citrate (17.40%), and the median lifespan of the filter was 31.06 hours (19.25,48.75). In addition, significant differences were observed in the electrolyte index, renal function index, and procalcitonin levels before and after treatment with a single filter (P<0.001). Multivariate logistic regression showed that the risk of non-selective cessation of sodium citrate anticoagulants was lower than that of heparin anticoagulation. Overall, CRRT is progressively becoming more prevalent in the treatment of severe burn patients. The lifespan of individual filters and total patient treatment duration showed a consistent upward trend. The filter's lifespan was notably greater during sodium citrate anticoagulation when compared to nafamostat mesylate and heparin, meanwhile notably reducing the risk of non-selective cessation. Therefore, we recommend sodium citrate for anticoagulation on patients without any contraindications.


[Community health: integration of primary care and public health competencies. SESPAS report 2010].
Primary care and public health have run on parallel tracks with scarce points of contact or coordination in community action to improve the population's health. If community health is defined as the "health of individuals and groups in a defined community, determined by the interaction of personal and familial factors and by the socioeconomic-cultural and physical environments" and of community intervention is defined as local action to improve community health, primary care and public health are the key players to implement this aim. However, their actions should take into account other local actors, including the population. The inclusion of community health as an objective of the health system highlights the need to achieve more coordinated and comprehensive action, and to introduce advances in several areas, which include training for health professionals, contracts to service providers, systems for defining service portfolios, and organizational aspects of services.


Effects of barbiturates on ATP-sensitive K channels in rat substantia nigra.
ATP-sensitive K channels are widely expressed in cytoplasmic membranes of neurons, and they couple cell metabolism to excitability. They are thought to be involved in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity by hyperpolarizing neurons and reducing excitability. Although barbiturates are often used in patients with brain ischemia, the effects of these agents on neuronal ATP-sensitive K channels have not been clarified. We studied the effects of thiopental and pentobarbital on surface ATP-sensitive K channels in principal neurons of rat substantia nigra pars compacta. Whole cell voltage- and current-clamp recordings were made using rat midbrain slices. ATP-sensitive K channels were activated by intracellular dialysis with an ATP-free pipette solution during perfusion with a glucose-free solution. When the pipette solution contained 4mM ATP and the perfusing solution contained 25 mM glucose, the membrane current at -60 mV remained stable. When intracellular ATP was depleted, hyperpolarization and an outward current developed slowly. Although thiopental did not affect the membrane current in the presence of ATP and glucose, it reversibly inhibited the hyperpolarization and outward current induced by intracellular ATP depletion at 100 and 300 microM. Thiopental reduced the ATP depletion-induced outward current by 4.7%, 36.7% and 87% at 30, 100 and 300 microM, respectively. The high dose of pentobarbital also exhibited similar effects on ATP-sensitive K channels. These results suggest that barbiturates at high concentrations but not at clinically relevant concentrations inhibit ATP-sensitive K channels activated by intracellular ATP depletion in rat substantia nigra.


Advances in Research on Chemical Constituents and Their Biological Activities of the Genus Actinidia.
Kiwi, a fruit from plants of the genus Actinidia, is one of the famous fruits with thousand years of edible history. In the past twenty years, a great deal of research has been done on the chemical constituents of the Actinidia species. A large number of secondary metabolites including triterpenoids, flavonoids, phenols, etc. have been identified from differents parts of Actinidia plants, which exhibited significant in vitro and in vivo pharmacological activities including anticancer, anti-inflammatory, neuroprotective, anti-oxidative, anti-bacterial, and anti-diabetic activities. In order to fully understand the chemical components and biological activities of Actinidia plants, and to improve their further research, development and utilization, this review summarizes the compounds extracted from different parts of Actinidia plants since 1959 to 2020, classifies the types of constituents, reports on the pharmacological activities of relative compounds and medicinal potentials.


Identifying Blunt Force Traumatic Injury on Thermally Altered Remains: A Pilot Study Using Sus scrofa.
In forensic scenarios involving homicide, human remains are often exposed to fire as a means of disposal and/or obscuring identity. Burning human remains can result in the concealment of traumatic injury, the creation of artifacts resembling injury, or the destruction of preexisting trauma. Since fire exposure can greatly influence trauma preservation, methods to differentiate trauma signatures from burning artifacts are necessary to conduct forensic analyses. Specifically, in the field of forensic anthropology, criteria to distinguish trauma from fire signatures on bone is inconsistent and sparse. This study aims to supplement current forensic anthropological literature by identifying criteria found to be the most diagnostic of fire damage or blunt force trauma. Using the skulls of 11 adult pigs (Sus scrofa), blunt force trauma was manually produced using a crowbar and flat-faced hammer. Three specimens received no impacts and were utilized as controls. All skulls were relocated to an outdoor, open-air fire where they were burned until a calcined state was achieved across all samples. Results from this experiment found that blunt force trauma signatures remained after burning and were identifiable in all samples where reassociation of fragments was possible. This study concludes that distinct patterns attributed to thermal fractures and blunt force fractures are identifiable, allowing for diagnostic criteria to be narrowed down for future analyses.


Subject versus experimenter control in the reaction to pain.
Although perceived control has been used as a means of reducing the reaction to pain, conceptually, much is still unclear. The purpose of this study was to clarify the effects of control as a mediating variable in the reaction to pain as a function of the predispositional variables of perceived self-efficacy and trait anxiety. Self-efficacy refers to the subject's premeasured, perceived ability to control his pain. The type of control provided either to the subject or the experimenter was varied over 5 independent groups. Predictability of occurrence of the pain stimulation was varied on a within-subject basis. Results mirrored the complexity of the problem. Overall, when subjects were given decisional control alone the largest reactions to pain were obtained. Subjects given decisional plus behavioral control yielded the lowest reactions to pain. Both self-efficacy and trait anxiety significantly were predictive of outcomes. Unexpectedly, experimenter control reduced the reaction to pain among those with high self-efficacy, but increased the reaction among those with low self-efficacy. Results of trait anxiety appear to indicate the need to keep anxiety within bounds. Adding responsibility such as control to an individual who is already anxious may increase the reaction to pain. In general, it appears that control that is perceived as inadequate may be worse than not having any control. The theoretical and methodological implications of these results were discussed.


Preferential blood flow to brainstem during generalized seizures in the newborn marmoset monkey.
The effect of generalized seizures on local cerebral blood flow was studied autoradiographically in 21 immature marmoset monkeys, using either [123I]- or [131I]isopropyliodoamphetamine. Generalized convulsions were induced in ketamine-anesthetized and awake monkeys with bicuculline and continued for 4-59 min. During convulsions in marmosets less than 3 weeks of age, there was a striking rearrangement of blood flow in favor of the brainstem pontomedullary region. The ratios of blood flow in pons-medulla to blood flow in cerebral cortex, putamen, ventroposterior thalamic nuclei, lateral geniculate nuclei, cerebellum and hemispheric white matter increased 1 1/2 to 2 times compared to controls. In seizure animals 4-8 weeks of age, the redistribution of blood flow to brainstem did not occur. Although metabolic acidosis developed after 30 min of bicuculline-induced seizures, mean arterial blood pressure, temperature, arterial pO2 and pCO2 did not differ significantly from controls, indicating that hypoxemia, hypercapnia and hypotension cannot explain the altered cerebral blood flow pattern. The redistribution phenomenon could be explained by more pronounced vasodilatation in brainstem than many other brain regions during generalized seizures in newborn monkeys. Lack of significant vasodilatation in forebrain structures such as cerebral cortex could contribute to neuronal damage by limiting substrate supply at a time of increased metabolic activity.


Benefits of bariatric surgery on spinal epidural lipomatosis: case report and literature review.
Spinal epidural lipomatosis is an abnormal accumulation of unencapsulated epidural fat causing compression of the neural elements. It can be divided into idiopathic and secondary. Secondary is often associated with chronic steroid use and endocrinopathies. Idiopathic has been associated with obesity. We report a 48-year-old man with obesity and a history of chronic back pain who developed idiopathic spinal epidural lipomatosis diagnosed by magnetic resonance imaging, which subsequently resolved completely after sleeve gastroplasty over a 6-month follow-up period.


Nonoperative Options for Management of Articular Cartilage Disease.
Nonoperative options for articular cartilage injury are pervasive but have not shown to be curative. Recommendations for low-impact exercise and weight loss provide benefit and are a foundation for the treatment of osteoarthritis. Judicious use of NSAIDs and acetaminophen can be appropriate for pain management. Topical NSAIDs may be a treatment option with fewer side effects than its oral counterpart. Additionally, viscosupplementation injections are useful for mild to moderate knee osteoarthritis, whereas short-term pain relief is provided by intra-articular corticosteroid injections. Future studies to individualize treatment options based on patient phenotype and genotype may hold promise.


[Modification of DNA damage in rat hepatocytes following whole-body roentgen radiation using cysteamine and 8-bromocaffeine].
Using the elastoviscosimetric method it was shown that the level of residual DNA double-strand breaks in rat hepatocytes depended on conditions of total-body X-irradiation: it increased in the presence of a sensitizer, 8-bromocaffeine and decreased in the presence of a protector, cysteamine. This correlation confirms a major role of fixed DNA double-strand breaks in the formation of a lethal effect in a cell.


Effects of nifedipine on forearm vascular resistance and venous capacitance in normal subjects and in patients with congestive heart failure.
The effects of oral nifedipine on limb hemodynamics were studied in 7 normal subjects, 8 patients with congestive heart failure and 2 patients who underwent sympathectomy of unilateral limb. Forearm venous capacitance remained unchanged both in normal subjects and in patients with congestive heart failure. In normal subjects, systemic vascular resistance decreased without change in forearm vascular resistance. On the other hand, both systemic and forearm vascular resistance decreased simultaneously in patients with congestive heart failure. In 2 patients with normal left ventricular function undergoing sympathectomy, limb vascular resistance decreased in the denervated side and increased in the contralateral innervated side. These findings indicate that the effects of nifedipine on forearm vascular resistance are dependent upon the circulatory state of the patient at the time the drug is administered, while venous dynamics were not changed by nifedipine, and that the difference in the density of sympathetic innervation results in a reordering of territorial blood flow by modifying the vasodilatation due to the calcium antagonistic action of nifedipine.


Paired-associate versus cross-situational: How do verbal working memory and word familiarity affect word learning?
Word learning is one of the first steps into language, and vocabulary knowledge predicts reading, speaking, and writing ability. There are several pathways to word learning and little is known about how they differ. Previous research has investigated paired-associate (PAL) and cross-situational word learning (CSWL) separately, limiting the understanding of how the learning process compares across the two. In PAL, the roles of word familiarity and working memory have been thoroughly examined, but these same factors have received very little attention in CSWL. We randomly assigned 126 monolingual adults to PAL or CSWL. In each task, names of 12 novel objects were learned (six familiar words, six unfamiliar words). Logistic mixed-effects models examined whether word-learning paradigm, word type and working memory (measured with a backward digit-span task) predicted learning. Results suggest better learning performance in PAL and on familiar words. Working memory predicted word learning across paradigms, but no interactions were found between any of the predictors. This suggests that PAL is easier than CSWL, likely because of reduced ambiguity between the word and the referent, but that learning across both paradigms is equally enhanced by word familiarity, and similarly supported by working memory.


Trajectories of urinary incontinence in childhood and bladder and bowel symptoms in adolescence: prospective cohort study.
To identify different patterns (trajectories) of childhood urinary incontinence and examine which patterns are associated with bladder and bowel symptoms in adolescence. Prospective cohort study. General community. The starting sample included 8751 children (4507 men and 4244 women) with parent-reported data on frequency of bedwetting and daytime wetting for at least three of five time points (4½, 5½, 6½, 7½ and 9½ years-hereafter referred to as 4-9 years). Study children provided data on a range of bladder and bowel symptoms at age 14 (data available for 5899 participants). Self-reported bladder and bowel symptoms at 14 years including daytime wetting, bedwetting, nocturia, urgency, frequent urination, low voided volume, voiding postponement, passing hard stools and low stool frequency. We extracted 5 trajectories of urinary incontinence from 4 to 9 years using longitudinal latent class analysis: (1) normative development of daytime and night-time bladder control (63.0% of the sample), (2) delayed attainment of bladder control (8.6%), (3) bedwetting alone (no daytime wetting) (15.6%), (4) daytime wetting alone (no bedwetting) (5.8%) and (5) persistent wetting (bedwetting with daytime wetting to age 9) (7.0%). The persistent wetting class generally showed the strongest associations with the adolescent bladder and bowel symptoms: OR for bedwetting at 14 years=23.5, 95% CI (15.1 to 36.5), daytime wetting (6.98 (4.50 to 10.8)), nocturia (2.39 (1.79 to 3.20)), urgency (2.10 (1.44 to 3.07)) and passing hard stools (2.64 (1.63 to 4.27)) (reference category=normative development). The association with adolescent bedwetting was weaker for children with bedwetting alone (3.69 (2.21 to 6.17)). Trajectories of childhood urinary incontinence are differentially associated with adolescent bladder and bowel symptoms. Children exhibiting persistent bedwetting with daytime wetting had the poorest outcomes in adolescence.


Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited.
Clinical practice reveals that therapy with angiogenesis inhibitors often does not prolong survival of cancer patients for more than months, because tumors elicit evasive resistance. In this issue of Cancer Cell, two papers report that VEGF inhibitors reduce primary tumor growth but promote tumor invasiveness and metastasis. These perplexing findings help to explain resistance to these drugs but raise pertinent questions of how to best treat cancer patients with antiangiogenic medicine in the future. We discuss here how VEGF inhibitors can induce such divergent effects on primary tumor growth and metastasis.


Perceptions About the Efficacy and Acceptability of Telephone and Video-Delivered Allied Health Care for Adults With Disabilities During the COVID-19 Pandemic: A Cross-sectional National Survey.
To investigate and compare perceptions about the efficacy and acceptability of allied health care delivered via telephone and video call for adults with disabilities during the COVID-19 pandemic. Cross-sectional national survey. Participants who accessed occupational therapy, physiotherapy, psychology, or speech pathology care via telephone or via video call from June to September 2020. Five hundred eighty-one adults with permanent or significant disabilities, or their carers, partners, or family members, who were funded by the Australian National Disability Insurance Scheme. Not applicable. Experiences (eg, safety, efficacy, ease of use) with telephone and video-delivered care. Data were analyzed by calculating response proportions and chi-square tests to evaluate differences in experiences between allied health professions and between telephone and video modalities. Responses were obtained for 581 adults with disabilities. There was no evidence of differences between experiences with telephone or video-delivered services or across allied health professions. Overall, 47%-56% of respondents found telehealth technology easy to use (vs 17%-26% who found it difficult), 51%-55% felt comfortable communicating (vs 24%-27% who felt uncomfortable), 51%-67% were happy with the privacy and/or security (vs 6%-9% who were unhappy), 74% were happy with the safety (vs 5%-7% who were unhappy), and 56%-64% believed the care they received was effective (vs 17% who believed it was ineffective). Despite this, 48%-51% were unlikely to choose to use telephone or video consultations in the future (vs 32%-36% who were likely). Adults with disabilities in Australia had generally positive experiences receiving allied health care via telehealth during the COVID-19 pandemic, although some experienced difficulties using and communicating via the technology. Findings indicated no differences between satisfaction with telephone or video modalities, or between physiotherapy, speech pathology, occupational therapy, or psychology services.


Clinical and molecular characterization of pediatric mitochondrial disorders in south of China.
Mitochondrial disorders (MDs) are genetic ailments affecting all age groups. Epidemiological data and frequencies of gene mutations in pediatric patients in China are scarce. This retrospective study assessed 101 patients with suspected MDs treated at the Neurology Department of Children's Hospital, Fudan University, in 2011-2017. Mitochondrial (mtDNA) and nuclear (nDNA) samples were assessed by long-range polymerase chain reaction (PCR)-based whole mtDNA sequencing and whole exome sequencing (WES) for identifying pathogenic mutations. Muscle samples underwent various staining protocols and immunofluorescence for detecting selected proteins. Seventeen mutations in the MT-TL1, MT-COX2, MT-ND4, MT, tRNA TRNE, MT-TN, MT-TK, MT-ATP6, MT-ND6, MT-ND3 and MT-CO3 genes were identified in 39 patients, of which m.3243A > G, m.3303C > T, m.8993T > C/G, m.9176T > C, and m.10191T > C were most common. Mitochondrial myopathy and MELAS were most common for m.3243A > G mutation. Four novel mutations were detected, including m.9478insT, m.5666T > C, m.8265T > C, and m.8380-13600 deletion mutations related to Leigh syndrome, mitochondrial myopathy and KSS, respectively. Thirty-three mutations in the TK2, POLG, IBA57, HADHB, FBXL4, ALDH5A1, FOXRED1, TPK1, NDUFAF5, NDUFAF7, NDUFV1, CARS2, PDHA1, and HIBCH genes were identified in 19 patients, including 23 currently unknown. Higher rates of TK2, POLG, IBA57, and HADHB mutations were found in nDNA-mutated MD compared with the remaining individuals. Besides, IBA57 c.286T > C (p.Y96H), TK2 c.497A > T (p.D166V) founder mutations critically contributed to MDs. Comprehensive genomic analysis plays a critical role in pediatric MD diagnosis. These data summarize the relative frequencies of different gene mutations in a large Chinese population, and identified 23 novel MD-associated nDNA and 4 novel mtDNA mutations.


The impact of national energy structure on the concentrations, environmental behavior, and sources of polycyclic aromatic hydrocarbons in riverine and coastal sediments of the Beibu Gulf, China.
In this study, polycyclic aromatic hydrocarbons (PAHs) were measured in sediments of the Beibu Gulf in 2017 to investigate sources and a risk assessment. The results showed the total PAH concentration (∑16PAHs) in sediments of the Beibu Gulf in 2017 (17.6 ± 16.7 ng g-1) was significantly lower than that in 2010 (47.8 ± 27.4 ng g-1). The ∑16PAHs concentrations varied spatially within the Beibu Gulf, impacted by point source pollution. The results of adsorption/desorption and water-air partitioning suggest that the environmental behavior of PAHs in the Beibu Gulf is affected by atmospheric deposition and sediment-water partitioning. A risk assessment showed that the PAHs in sediments were within a safety threshold. Three source apportionment methods show that oil spills and oil and biomass burning were the most important (>83.8%) sources of PAHs in sediments of the Beibu Gulf.


How to use biomarkers efficiently in acute kidney injury.
We discuss the performance of novel biomarkers in acute kidney injury (AKI). Comparison of the areas under the receiver operating characteristic curves of several biomarkers with some clinical and/or routine biochemical outcome parameters reveals that none of the biomarkers has demonstrated a clear additional value beyond the traditional approach in clinical decision making in patients with AKI. Unscrutinized use of these biomarkers may distract from adequate clinical evaluation and carries the risk of worse instead of better patient outcome.


Mediator subunit Med15 dictates the conserved "fuzzy" binding mechanism of yeast transcription activators Gal4 and Gcn4.
The acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in transcription repression and activation through binding to Gal80 repressor and Mediator subunit Med15. The activation function of Gal4 arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds the Mediator subunit Med15 using a "fuzzy" protein interface. Remarkably, comparison of chemical shift perturbations shows that Gal4 and Gcn4, two intrinsically disordered ADs of different sequence, interact nearly identically with Med15. The finding that two ADs of different sequence use an identical fuzzy binding mechanism shows a common sequence-independent mechanism for AD-Mediator binding, similar to interactions within a hydrophobic cloud. In contrast, the same region of Gal4 AD interacts strongly with Gal80 via a distinct structured complex, implying that the structured binding partner of an intrinsically disordered protein dictates the type of protein-protein interaction.


The amount of metastatic melanoma in a sentinel lymph node: does it have prognostic significance?
The amount of metastatic disease in the sentinel lymph node (SLN) is examined as a prognostic factor in malignant melanoma. SLN mapping was performed on 592 patients with stage I and II malignant melanoma from March 1, 1994, through December 31, 1999. One hundred four patients were found to have 134 sentinel SLNs containing metastatic melanoma. The slides were reviewed, and the size of the metastatic melanoma in each SLN was measured. The size of the metastatic deposit was defined as macrometastasis (>2 mm), micrometastasis (< or =2 mm), a cluster of cells (10-30 grouped cells) in the subcapsular space or interfollicular zone, or isolated melanoma cells (1 to > or =20 individual cells) in subcapsular sinuses. The number of metastases in each SLN was isolated melanoma cells, n = 5 (3.7%); cluster of cells, n = 35 (26.1%); < or =2 mm, n = 45 (33.6%); and >2 mm, n = 49 (36.7%). Seventy-nine patients (76%) had a single positive SLN. The size of the largest nodal metastasis was used to stratify patients with multiple positive SLNs. The overall 3-year survival for patients with SLN micrometastases was 90%, versus 58% for patients with SLN macrometastases (P =.004). The amount of metastatic melanoma in an SLN is an independent predictor of survival. Patients with SLN metastatic deposits >2 mm in diameter have significantly decreased survival.


Recovery High Schools: Students and Responsive Academic and Therapeutic Services.
This article reviews findings from the authors' studies of recovery high schools (RHS), including a 1995 program evaluation of a school in New Mexico (Moberg and Thaler, 1995), a 2006-09 descriptive study of 17 recovery high schools (Moberg and Finch, 2008), and presents early findings from a current study of the effectiveness of recovery high schools. Descriptive and qualitative findings are presented. The focus is on characteristics of RHS students and, in light of those student characteristics, findings regarding academic and recovery support programming in recovery high schools.