Gastric insufflation during cardiopulmonary resuscitation: A study in human cadavers.
Bag-valve-mask ventilation is the first-line ventilation method during cardiopulmonary resuscitation (CPR). Risks include excessive volume delivery and gastric insufflation, the latter increasing the risk of pneumonia. The efficacy of ventilation can also be reduced by airway closure. We hypothesized that continuous chest compression (CC) could limit the risk of gastric insufflation compared to the recommended 30:2 interrupted CC strategy. This experimental study was performed in human "Thiel" cadavers to assess the respective impact of discontinuous vs. continuous chest compressions on gastric insufflation and ventilation during CPR. The 30:2 interrupted CC technique was compared to continuous CC in 5 non-intubated cadavers over a 6 min-period. Flow and Airway Pressure were measured at the mask. A percutaneous gastrostomy allowed measuring the cumulative gastric insufflated volume. Two additional cadavers were equipped with esophageal and gastric catheters instead of the gastrostomy. For the 7 cadavers studied (4 women) median age of death was 79 [74-84] years. After 6 min of CPR, the cumulative gastric insufflation measured in 5 cadavers was markedly reduced during continuous CC compared to the interrupted CC strategy: (1.0 [0.8-4.1] vs. 5.9 [4.0-5.6] L; p < 0.05) while expired minute ventilation was slightly higher during continuous than interrupted CC (1.9 [1.4-2.8] vs. 1.6 [1.1-2.7] L/min; P < 0.05). In 2 additional cadavers, the progressive rise in baseline gastric pressure was lower during continuous CC than interrupted CC (1 and 2 cmH2O vs. 12 and 5.8 cmH2O). Continuous CC significantly reduces the volume of gas insufflated in the stomach compared to the recommended 30:2 interrupted CC strategy. Ventilation actually delivered to the lung is also slightly increased by the strategy.


Optimizing monosaccharide production from liquid hot water pretreatment and enzymatic hydrolysis of grass-clover press cake.
In the present study, clover-grass press cake was treated by liquid hot water at temperatures of 180-200 °C for a reaction time of 5-10 min. Evaluation of pretreatments was based on the monosaccharide yield after enzymatic hydrolysis of the pretreated slurry and solid fraction, respectively. Extraction of up to 48% hemicellulose and 4% cellulose was observed during pretreatment. The optimal pretreatment conditions were identified as 190 °C and 10 min resulting in monosaccharide yields of 90% and 73% of the theoretical maximum by slurry and solid conversion, respectively. At optimal conditions, the C6 monosaccharide yield (83-90%) was fairly equal compared to the C5 monosaccharide yield (56-89%), which increased by slurry conversion due to near-complete monomerization of soluble xylo-oligosaccharides. In this study, we showed that clover-grass press cake possesses considerable potential as feedstock for production of fermentable sugars in a biorefinery context.


HSG1, a grape Bcl-2-associated athanogene, promotes floral transition by activating CONSTANS expression in transgenic Arabidopsis plant.
HSG1 (Heat shock-induced gene 1) is one of the high-temperature-induced proteins in grapevine. Sequence analysis has demonstrated that HSG1 is a grape Bcl-2-associated athanogene (BAG) that contains IQ and BAG domains in its sequence. HSG1 expression was not detected in leaves without heat treatment, while tendrils, stems, flowers, and berries expressed HSG1 even without heat treatment. By heat treatment at 45°C for 60 min, HSG1 expression was upregulated in both leaves and berries. HSG1-overexpressing Arabidopsis plant remained viable even after exposure to extremely high temperatures. Although no morphological changes were observed, the HSG1-overexpressing Arabidopsis plant exhibited faster floral transition than the control plant. Analysis of the transcription profile of HSG1-overexpressing seedling by cDNA microarray and quantitative RT-PCR demonstrated that the gene expression of the flowering promoter, CONSTANS (CO), in the photoperiod pathway was up-regulated in the seedling. Importantly, the overexpression of HSG1 increased CO expression by ~400% compared with the control seedling. Meanwhile, heat treatment upregulated grape CO expression in grape leaves. Our study provides the possibility that plant BAG protein may be related to the regulation of floral transition by activating CO expression in the photoperiod pathway.


Brown adipose tissue and regulation of human body weight.
Approximately 30% of the global population is affected by obesity. Traditional non-surgical measures for weight loss have limited efficacy and tolerability. Therefore, there is a need for novel, effective therapies. Brown adipose tissue (BAT) has been implicated in physiological energy expenditure, indicating that it could be targeted to achieve weight loss in humans. The use of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography-computed tomography-(PET-CT) imaging has enabled the discovery of functionally active BAT in the supraclavicular, subclavian, and thoracic spine regions of human adults. This review aims to discuss the reasons behind the renewed interest in BAT, assess whether it is metabolically important in humans, and evaluate its feasibility as a therapeutic target for treating obesity. PubMed Central, Europe PMC, Medline. In vivo studies have shown that BAT activity is regulated by thyroid hormones and the sympathetic nervous system. Furthermore, BAT uniquely contains uncoupling protein 1 (UCP1) that is largely responsible for non-shivering thermogenesis. Cold exposure can increase BAT recruitment through the browning of white adipose tissue (WAT); however, this technique has practical limitations that may preclude its use. Currently available medicines for humans, such as the β3-adrenergic receptor agonist mirabegron or the farnesoid X receptor agonist obeticholic acid, have generated excitement, although adverse effects are a concern. Capsinoids represent a tolerable alternative, which require further investigation. The use of currently available BAT-activating agents alone is unlikely to achieve significant weight loss in humans. A combination of BAT activation with physical exercise and modern, successful dietary strategies represents a more realistic option.


Lias overexpression alleviates pulmonary injury induced by fine particulate matter in mice.
Oxidative stress and inflammation are mechanisms underlying toxicity induced by fine particulate matter (PM2.5). The antioxidant baseline of the human body modulates the intensity of oxidative stress in vivo. This present study aimed to evaluate the role of endogenous antioxidants in alleviating PM2.5-induced pulmonary injury using a novel mouse model (LiasH/H) with an endogenous antioxidant capacity of approximately 150% of its wild-type counterpart (Lias+/+). LiasH/H and wild-type (Lias+/+) mice were randomly divided into control and PM2.5 exposure groups (n = 10), respectively. Mice in the PM2.5 group and the control group were intratracheally instilled with PM2.5 suspension and saline, respectively, once a day for 7 consecutive days. The metal content, major pathological changes in the lung, and levels of oxidative stress and inflammation biomarkers were examined. The results showed that PM2.5 exposure induced oxidative stress in mice. Overexpression of the Lias gene significantly increased the antioxidant levels and decreased inflammatory responses induced by PM2.5. Further study found that LiasH/H mice exerted their antioxidant function by activating the ROS-p38MAPK-Nrf2 pathway. Therefore, the novel mouse model is useful for the elucidation of the mechanisms of pulmonary injury induced by PM2.5.


Expression of a cysteine-rich protein (CRP) encoding gene during early development of the trout.
Members of the cysteine-rich protein (CRP) define a subclass of LIM-only proteins implicated mainly in muscle differentiation. Until now, very little is known concerning the expression of CRP encoding genes during vertebrate development. We describe here the isolation of a trout (Oncorhynchus mykiss) gene encoding a cysteine-rich protein (TCRP) and the pattern of its mRNA accumulation during embryogenesis, focusing on somitogenesis. TCRP encodes a putative protein with two LIM domains linked to a short glycine-rich region that displays 86%, 76%, 67% identity with chicken CRP2, CRP1 and MLP/CRP3 proteins, respectively. Whole-mount in situ hybridisation showed that TCRP transcript is first detected just before somitogenesis in the paraxial mesoderm, while it is absent in the axial structures. During somitogenesis, the expression of TCRP was observed caudally in the elongating presomitic mesoderm and in the last formed somites. The labelling for TCRP was found to fade as the somites mature. At the end of the somitogenesis, TCRP transcripts accumulation was restricted to pronephros and bronchial arches.


Endogenous lectins from cultured cells. Isolation and characterization of carbohydrate-binding proteins from 3T3 fibroblasts.
Extracts of cultured 3T3 fibroblasts, obtained by homogenization and Triton X-100 solubilization, were fractionated on Sepharose columns covalently derivatized with asialofetuin. Three distinct carbohydrate-binding proteins (CBPs) were purified from the material bound to the affinity column: CBP35 (Mr = 35,000), CBP16 (Mr = 16,000), and CBP13.5 (Mr = 13,500). These CBPs were similar in several key properties. (a) They showed agglutination activity when assayed with rabbit erythrocytes; (b) they all appear to specifically recognize galactose-containing glycoconjugates; (c) they have low isoelectric points, pI 4.5-4.7; (d) their binding activities are rapidly lost in the absence of beta-mercaptoethanol; (e) the CBPs do not interact with each other, and the fractionated proteins can bind to asialofetuin independent of associated polypeptides; and (f) none of the proteins tend to self-associate to form oligomers of identical subunits. Comparisons of these and other properties of the CBPs suggest that CBP16 and CBP13.5 may be the murine counterparts of lactose-specific lectins previously identified in electric eel and in several bovine and avian tissues. In contrast, it appears that CBP35 represents a newly identified protein capable of binding to galactose-containing carbohydrates.


Adolescent affective psychopathic traits: the long-term outcomes of mother-infant attachment across 14 years.
Affective psychopathic traits have been associated with increased violence and aggression. The scholarly interest in the pathways leading to affective psychopathic traits in adolescence has been growing. Infant attachment security may be one of the early life factors that contribute to the development of affective psychopathic traits. In this study, we test the infant attachment styles measured with the Strange Situation Procedure as a predictor of adolescent affective psychopathic traits measured in three dimensions: remorselessness, unemotionality, and callousness, among 1149 families in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (SECCYD). Propensity scores for the four attachment styles were estimated with iterative tree-based regression models. After accounting for the potential confounding effects of demographic characteristics and child temperament with the inverse probability of treatment weighting, weighted generalized linear models revealed the association between insecure/avoidant attachment style measured one year after childbirth and higher levels of remorselessness, unemotionality, and callousness at 15 years. These findings provide insights into the long-term outcomes for attachment relationships established in early life.


Phytochemical Analysis, GC-MS Profiling, and In Vitro Evaluation of Biological Applications of Different Solvent Extracts of Leonotis nepetifolia (L.) R.Br. Flower Buds.
Leonotis nepetifolia (L.) R.Br. is a medicinally important herb belonging to the family Lamiaceae. The plant is typically found in tropical regions, and its leaf and root extracts are renowned for their ethno-botanical and therapeutic applications. This study was designed to determine the presence of various bioactive components, and to evaluate antibacterial, antifungal, antioxidant, and anti-proliferative activities. The preliminary phytochemical screening and gas chromatography-mass spectrometry (GC-MS) analysis of different solvent extracts revealed the presence of various bioactive compounds, of which methanol extract showed 24 compounds, petroleum ether extract revealed 26 compounds, and 24 compounds in hexane extracts. The major bioactive components including λ-sitosterol (16.20 %) in methanol extract, 1-nonadecanol (15.48 %) in petroleum extract, and eicosane (13.22 %) in hexane extract have been reported with various bio-therapeutic applications. In addition, the flower bud methanolic extract of L. nepetifolia exhibited inhibitory potential against all tested bacterial and fungal pathogens. The DPPH radical scavenging assay revealed that methanolic extract possessed the highest antioxidant activity. The scavenging activity increased in a concentration-dependent manner, as indicated by a 74 % inhibition rate at 1000 µg/ml. Furthermore, the in vitro cytotoxic effects of the methanolic extract on the HepG2 cell line were evaluated. The IC50 value of methanolic extract against HepG2 cells was determined to be 83.28 µg/ml. The findings reveal that different solvent extracts of L. nepetifolia flower buds contain a significant amount of various bioactive phytochemicals with antioxidant and anticancer activities; and thus, the plant could serve as a potential source of pharmacological applications.


Hemophagocytic lymphohistiocytosis and congenital factor VII deficiency: a case report.
Hemophagocytic lymfohistiocytosis (HLH) is a rare, life-threatening hyperinflammation, characterized by immune system over-activation resulting in hemophagocytosis. HLH could appear as a primary disease caused by mutations of immune-regulatory genes, or develop as a result of viral or bacterial infections, or malignancy. Congenital factor VII (FVII) deficiency is a rare autosomal recessive disorder characterized by prolonged prothrombin time (PT) and low FVII, which may increase bleeding risk. A 50-year-old woman was admitted for a fever persisted for 20 days, presenting with cytopenia, high hyperferritinemia, low activity of NK cells. Bone marrow aspiration showed hemophagocytosis. CT scanning found pulmonary infection. EBV and CMV were not detected. Genetic scanning did not find pathogenic mutation of a HLH NGS panel including 26 genes. This patient was treated as recommended by the HLH 2004 Guidelines. Coagulation tests identified FVII deficiency. Genetic analysis of F7 gene in the patient and her family members identified recurrent compound heterozygous F7 c.64 + 5G > A and c.1224 T > G (p.His408Gln) mutations in this patient and her brother who showed postoperative hemorrhage after surgical resection of renal cell carcinoma. Heterozygotes in this family were asymptomatic. To our knowledge, this is the first report of HLH in combination with congenital FVII deficiency in Chinese population.


Dermatological indicators of coronary risk: a case-control study.
We examined the association of dermatological signs such as baldness, thoracic hairiness, hair greying and diagonal earlobe crease with the risk of myocardial infarction in men under the age of 60 years. A hospital-based, case-control study included 842 men admitted for the first non-fatal myocardial infarction, the controls were 712 men admitted with noncardiac diagnoses, without clinical signs of coronary disease. The relative risks were estimated as odds ratios. Logistic regression was used to control for the confounding variables. Baldness, thoracic hairiness and earlobe crease were approximately 40% more prevalent in cases (P<10(-6) in each case). In both cases and controls, baldness and thoracic hairiness were frequently coexistent, as well as hair greying and earlobe crease (P<10(-4) in each case). After allowing for age and other established coronary risk factors, the relative risk of myocardial infarction for fronto-parietal baldness compared with no hair loss was 1.77 (95% CI 1.27-2.45) and it was 1.83 (95 CI 1.4-2.3) for men with thick, extended thoracic hairiness. The presence of a diagonal earlobe crease yielded a relative risk of 1.37 (95% CI 1.25-1.5), while hair greying was associated with myocardial infarction only in men under the age of 50 years. It appears that baldness, thoracic hairiness and diagonal earlobe crease indicate an additional risk of myocardial infarction in men under the age of 60 years, independently of age and other established coronary risk factors.


The inappropriate application of the regression Langmuir Qm for adsorption capacity comparison.
The Langmuir equation, the best known adsorption model in the past century, was extensively applied to describe adsorption isotherms. The saturated adsorption amount (Qm) obtained from the Langmuir model is an essential index to evaluate the maximum adsorption capacity of the adsorbent, which was assumed to be irrelevant to the aqueous concentration of the adsorbate. Adsorption isotherms of cadmium onto soil and biochar were performed in the current study, and the regression Langmuir Qm was demonstrated to be highly dependent on the aqueous concentration. The regression Qm increased from 0.066 to 2.17 mg·g-1 (by ~3-fold) for the selected soil, and from 2.12 to 48.4 mg·g-1 (by ~23-fold) for the chosen biochar when the highest initial aqueous concentration increased from 2.34 to 887 mg·L-1. One inappropriate application for comparison of the regression Langmuir Qm as the adsorption capacity is found, i.e., it is difficult to directly compare the regression Qm without neither a saturated isotherm nor considering the experimental conditions. It is also very hard to accurately predict adsorption behavior by the regressed Langmuir model obtained from a partial adsorption isotherm. It is suggested to pay more attention to the difference between the saturated adsorption capacity and the regression Qm value derived from one unsaturated isotherm.


The Mechanism of SNHG8/Microrna-421-3p/Sorting Nexin 8 Axis on Dopaminergic Neurons in Substantia Nigra in a Mouse Model of Parkinson's Disease.
Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the aging population. Particularly, long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in PD, while the role of lncRNA SNHG8 in PD remains to be further explored. C57BL/6 mice were induced by rotenone to establish a PD model in vivo, and then the dopaminergic (DA) neuronal damage and locomotor dysfunction in rotenone-treated mice were evaluated. Murine DA cell line MN9D was treated with rotenone to establish a cellular PD model in vitro. Then, the viability, apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells were assessed. Expression levels of SNHG8, microRNA-421-3p (miR-421-3p), and sorting nexin 8 (SNX8) in the substantia nigra (SN) of PD mice and rotenone-treated MN9D cells were detected. The interaction between SNHG8 and miR-421-3p, and the targeting relationship between SNX8 and miR-421-3p were confirmed. SNHG8 and SNX8 expression levels were decreased while miR-421-3p expression level was increased in the SN of PD mice and rotenone-treated MN9D cells. Upregulated SNHG8 ameliorated dopaminergic neuron damage and locomotor dysfunction in PD mice. Meanwhile, upregulated SNHG8 enhanced viability, diminished apoptosis, and alleviated mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells. Mechanistically, SNHG8 bound to miR-421-3p, and miR-421-3p targeted SNX8. Overexpressed SNHG8 downregulates miR-421-3p to alleviate rotenone-induced dopaminergic neuron injury in PD via upregulating SNX8.


Ventral rupture of the penile tunica albuginea and urethra distal to the sigmoid flexure in a bull.
A 4-year-old Limousin bull sustained a rupture of the ventral aspect of the tunica albuginea of the penis, 20 cm distal to the distal bend of the sigmoid flexure. The corpus spongiosum penis and urethra apparently ruptured at the same time.


Infantile and Noninfantile Desmoplastic Astrocytoma and Ganglioglioma: Only Different Age of Onset?
The purpose of this study was to investigate clinical, pathological, and prognostic discrepancies between infantile and noninfantile desmoplastic astrocytoma/ganglioglioma patients. From January 2012 to December 2019, we retrospectively reviewed patients aged <18 years who underwent craniotomies at Beijing Tiantan Hospital. Patients diagnosed with desmoplastic infantile astrocytoma and ganglioglioma (DIA/DIG) were included. The group consisted of 9 infantile patients and 8 noninfantile patients. The mean age of onset was 30.11 months in infantile patients and 103.75 months in noninfantile patients. Comparing with infantile patients, noninfantile patients had a mild female predominance (P = 0.335). The most common presentation in noninfantile patients was seizure (n = 4, 50%), whereas abnormal head circumference (n = 3, 33.3%) was the most common presentation in the infantile group. All cases showed a ki-67 index <2%. Preoperative tumor volume in infantile patients (213.98 cm3) was larger than that in noninfantile patients (21.99 cm3) (P = 0.043). Gross total resection was achieved in 5 (55.6%) infantile patients and 6 (75%) noninfantile patients (P = 0.62). All patients are alive by last follow-up visit, and 1 infantile patient recurred 8 months postoperative. Infantile and noninfantile patients with DIA/DIGs share similar clinical and histopathological features. Compared with infantile patients, noninfantile patients tend to have different symptom predominance. Lesions in noninfantile patients are prone to present with different cystic-solid patterns and smaller volume. Patients with DIA/DIGs have favorable prognosis regardless of extent of resection.


Mucosal IgA response to rectally administered antigen formulated in IgA-coated liposomes.
Ferritin, a soluble model antigen, was used to test whether liposomes can provide an effective delivery vehicle for mucosal immunization via the rectum, and whether the local colonic/rectal secretory immune response to antigen in liposomes can be enhanced by immunoadjuvants. The colonic/rectal IgA response to liposomal ferritin was significantly enhanced over the response to free ferritin but only when cholera toxin (CT) was present as adjuvant. The presence of IgA on the liposome surface increased the uptake of liposomes into Peyer's patch mucosa, and the local rectal/colonic immune response to ferritin about 5-fold over uncoated liposomes. These results show that (1) liposomes co-administered with immunoadjuvants can be used for mucosal immunization via the rectum. (2) Cholera toxin is an effective immunoadjuvant in the rectal/colonic mucosa. (3) IgA can enhance the local secretory immune response to antigen in liposomes, apparently by increasing liposome uptake via M cells.


Chemical reduction of an unbuffered nitrate solution using catalyzed and uncatalyzed nanoscale iron particles.
Uncatalyzed and catalyzed nanoscale Fe(0) systems were employed for the denitrification of unbuffered 40 mgN L(-1) nitrate solutions at initial neutral pH. Compared to microscale Fe(0) (<100 mesh), the efficiency and rate of nitrate removal using uncatalyzed and catalyzed nano-Fe(0) were highly promoted, in which the maximum promoted rate was obtained using copper-catalyzed nano-Fe(0) (nano-Cu/Fe). Nitrate first-order degradation rate constants (k(obs)) decreased significantly (>70%) with aged nano-Fe(0) and aged nano-Cu/Fe, and were recovered with NaBH(4) as reductants at levels of about 85 and 75%, respectively. Activation energies (E(a)) of nitrate reduction over the temperature range of 10-60 degrees C were 42.5 kJ mol(-1) for microscale Fe(0), 25.8 kJ mol(-1) for nano-Fe(0) and 16.8 kJ mol(-1) for nano-Cu/Fe. Unlike microscale Fe(0), the kinetics of denitrification by nano-Fe(0) and nano-Cu/Fe began to show characteristics of mass transport in addition to chemical reaction control. Ammonium was the predominant end product in all the systems. However, as for nitrite, 40% of the degraded nitrate persisted in the nano-Cu/Fe system. Thus, relative to nano-Cu/Fe, nano-Fe(0) is a potential reductant for denitrification of groundwater as far as toxic nitrite generation is concern.


Association Between Lack of Insight and Prefrontal Serotonin Transporter Availability in Antipsychotic-Free Patients with Schizophrenia: A High-Resolution PET Study with [11C]DASB.
Previous studies suggested a link between serotonergic neurotransmission and impaired insight in schizophrenia. In this study, we examined the relationship between serotonin transporter (SERT) availability in regions of the prefrontal cortex (dorsolateral, ventrolateral, ventromedial, and orbitofrontal cortices) and insight deficits in antipsychotic-free patients with schizophrenia using high-resolution positron emission tomography (PET) with [11C]DASB. Nineteen patients underwent [11C]DASB PET and 7-Tesla magnetic resonance imaging scans. To assess SERT availability, the binding potential with respect to non-displaceable compartment (BPND) was derived using the simplified reference tissue model. Patients' level of insight was assessed using the Insight and Treatment Attitude Questionnaire (ITAQ). The relationship between ITAQ scores and [11C]DASB BPND values was examined using the region-of-interest (ROI)- and voxel-based analyses with relevant variables as covariates. The prefrontal cortex and its four subregions were selected as a priori ROIs since the prefrontal cortex has been implicated as the critical neuroanatomical substrate of impaired insight in schizophrenia. The ROI-based analysis revealed that the ITAQ illness insight dimension had significant negative correlations with the [11C]DASB BPND in the left dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ treatment insight dimension had significant negative correlations with the [11C]DASB BPND in the bilateral dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ total score showed significant negative correlations with the [11C]DASB BPND in the bilateral prefrontal cortex and three subregions (dorsolateral, ventrolateral, and orbitofrontal cortices). A supplementary voxel-based analysis corroborated a significant negative association between the ITAQ score and the [11C]DASB BPND in the prefrontal cortices. Our study provides in vivo evidence of significant negative correlations between insight deficits and prefrontal SERT availability in patients with schizophrenia, suggesting significant involvement of prefrontal serotonergic signaling in impaired insight, one of the core symptoms of schizophrenia.


Morphometry of the ear in Down's syndrome subjects. A three-dimensional computerized assessment.
The three-dimensional coordinates of 13 soft-tissue landmarks on the ears were obtained by a computerized digitizer in 28 subjects with Down's syndrome aged 12-45 years, and in 449 sex, age and ethnic group matched controls. From the landmarks, left and right linear distances (ear width and length), ratios (ear width-to-ear length), areas (ear area), angles (angle of the auricle versus the facial midplane) and the three-dimensional symmetry index were calculated. For both males and females, all linear dimensions and areas were significantly (Analysis of Variance, P < 0.001) larger in the reference subjects than in the subjects with Down's syndrome. All values significantly increased as a function of age (P < 0.05); the increment was larger in the reference subjects than in the subjects with Down's syndrome. On both sides of the face, the subjects with Down's syndrome had larger ear width-to-ear length ratios, and larger angles of the auricle versus the facial midplane than the reference subjects. The three-dimensional symmetry index was significantly larger in the reference subjects and in the older persons. In conclusion, ear dimensions, position and shape significantly differed in subjects with Down's syndrome when compared to sex, age and ethnic group matched controls. Some of the differences were sex and age related.


Translation, Cross-Cultural Adaptation, and Psychometric Evaluation of the Third Version of the Atlanta Heart Failure Knowledge Test.
Background and Purpose: This study is aimed at translating the third version of the Atlanta Heart Failure Knowledge Test (AHFKTv3) into the Persian language and evaluating its psychometric properties. Methods: In this methodological study, the AHFKTv3 was translated into Persian and its face, content, construct validity, and reliability were assessed. Results: The content validity of AHFKTv3 items was >0.78 and the validity of the instrument was 0.96. The standardized factor loading value of all items, except for item 16, was >0.3. The scores of the AHFKTv3 and European Heart Failure Self-Care Behavior Scale had a significant correlation with each other (p < .001). The AHFKTv3 score had a significant relationship with the educational level. The Kuder-Richardson Formula 20 coefficient was 0.908. Conclusion: The Persian AHFKTv3 is a valid and reliable instrument for assessing HF-related knowledge; therefore, it can be used in nursing practice to identify and address the deficits aiming for better patient care and in research to evaluate treatment and healthcare programs.


Amino-Acid-Assisted Synthesis of Hollow Hierarchical FER Zeolite with Improved Catalytic Performance.
Hierarchical zeolites are highly-desired catalysts in the petrochemical industry due to their shorter diffusion length, faster diffusion rate, and better accessibility to active acid sites compared with conventional zeolites. Herein, we report a simple amino-acid-assisted method to synthesize urchin-like hollow hierarchical FER zeolites with abundant mesopores and macroporous inner cavities. An amino acid (i. e. L-lysine) is used to facilitate the agglomeration of primary gel nanoparticles. The preferential nucleation and crystal growth at the external surfaces together with the lagged crystallization of the inner core of the agglomerates results in the formation of hollow inner cavities after the exhaustion of interior materials. Thanks to the unique hierarchical structure and more accessible acid sites, the hollow hierarchical FER zeolite exhibits improved catalytic performance over the conventional one in the skeletal isomerization of 1-butene to isobutene.


Glass-coated ferromagnetic microwire-induced magnetic hyperthermia for in vitro cancer cell treatment.
Limitations in effectiveness and the invasive nature of current cancer treatment options emphasize the need for further clinical advancements. Among other approaches, targeted hyperthermia is as a new strategy aimed at targeting cancerous cells to improve the efficacy of radiotherapy or cytotoxic drugs. However, the testing of magnetic vehicles has mainly focused on the use of nanoparticles. In this work, Fe77B10Si10C3 glass-coated amorphous magnetic microwires were assessed for the first time as magnetic vehicles with high potential for the localized heating of osteosarcoma cells by means of an AC magnetic field. The results from the in vitro assays performed inside a microfluidic device demonstrated the ability of these magnetic microwires to induce malignant cell death. Exposing the system to different magnetic fields for less than 1 h provoked a reduction up to 89% of the osteosarcoma cell population, whereas healthy myoblastoma cells remained nearly unaffected. The proposed technology demonstrates in vitro the effectiveness of these microwires as vehicles for targeted magnetic hyperthermia.


Relative frequencies of polymorphisms of variation in Block 2 repeats and 5' recombinant types of Plasmodium falciparum msp1 alleles.
The mechanisms producing the genetic polymorphism at Plasmodium falciparum merozoite surface antigen-1 locus (pfmsp1) include the insertion and deletion of the different type of dimorphic Block 2 9-nucleotide repeat units as well as the intragenic recombination. To study relative occurrence frequencies of these two distinct mechanisms, we have developed a sensitive PCR strategy to identify both 5' recombinant types and the number of Block 2 repeats from the same sample. This method can specifically detect the target 5' recombinant type (Blocks 2-6) at the sensitivity of 1-4 copies of the pfmsp1. Applying the new method to field isolates from the Solomon Islands enabled us to identify six different 5' recombinant types and variation in Block 2 repeat number in three of them, thus distinguishing 10 different alleles. Distribution of these alleles in local three villages in the study area suggests that frequencies of variation in the number of Block 2 9-bp repeats and recombination events within Blocks 2-6 are mutually independent and the frequency of repeat variation is relatively high as compared to that of recombination events at the pfmsp1 locus in P. falciparum populations from the Solomon Islands.


Structure of a peptide antifreeze and mechanism of adsorption to ice.
Sequence studies of an alpha-helical peptide antifreeze isolated from winter flounder have revealed the presence of clusters of polar amino acids separated by long sequences of alanine. Most of the polar residues are threonine and aspartate and are separated by 4.5 A, a repeat distance that also separates the oxygens in the ice lattice along the a-axis of an ice crystal. Such a lattice match suggests that the peptide binds to ice by means of hydrogen binding.


Electrocardiographic changes in combined electrolyte depletion.
Cardiac action potential is affected by extracellular gradients in potassium, calcium, and magnesium with resultant electrocardiographic changes varying from subtle findings to marked repolarization abnormalities. This report presents marked electrocardiographic changes resulting from a combination of electrolytes depletion in a patient with bulimia and anorexia nervosa.


Volumetric dimensional changes of dental light-cured dimethacrylate resins after sorption of water or ethanol.
This study evaluated the influence of water and ethanol sorption on the volumetric dimensional changes of resins prepared by light curing of Bis-GMA, Bis-EMA, UDMA, TEGDMA or D(3)MA. The resin specimens (15mm diameterx1mm height) were immersed in water or ethanol 37+/-1 degrees C for 30 days. Volumetric changes of specimens were obtained via accurate mass measurements using Archimedes principle. The specimens were reconditioned by dry storage in an oven at 37+/-1 degrees C until constant mass was obtained and then immersed in water or ethanol for 30 days. The volumetric changes of specimens were determined and compared to those obtained from the first sorption. Resins showed similar volume increase during the first and second sorptions of water or ethanol. The volume increase due to water absorption is in the following order: poly-TEGDMA>poly-Bis-GMA>poly-UDMA>poly-Bis-EMA>poly-D(3)MA. On the contrary, the order in ethanol is poly-Bis-GMA>poly-UDMA>poly-TEGDMA>poly-Bis-EMA approximately poly-D(3)MA. The volume increase was found to depend linearly on the amount of water or ethanol absorbed. In the choice of monomers for preparation of composite resin matrix the volume increase in the resin after immersion in water or ethanol must be taken into account. Resins of Bis-EMA and D(3)MA showed the lowest values.


Identification of diagnostic genes for both Alzheimer's disease and Metabolic syndrome by the machine learning algorithm.
Alzheimer's disease is the most common neurodegenerative disease worldwide. Metabolic syndrome is the most common metabolic and endocrine disease in the elderly. Some studies have suggested a possible association between MetS and AD, but few studied genes that have a co-diagnostic role in both diseases. The microarray data of AD (GSE63060 and GSE63061 were merged after the batch effect was removed) and MetS (GSE98895) in the GEO database were downloaded. The WGCNA was used to identify the co-expression modules related to AD and MetS. RF and LASSO were used to identify the candidate genes. Machine learning XGBoost improves the diagnostic effect of hub gene in AD and MetS. The CIBERSORT algorithm was performed to assess immune cell infiltration MetS and AD samples and to investigate the relationship between biomarkers and infiltrating immune cells. The peripheral blood mononuclear cells (PBMCs) single-cell RNA (scRNA) sequencing data from patients with AD and normal individuals were visualized with the Seurat standard flow dimension reduction clustering the metabolic pathway activity changes each cell with ssGSEA. The brown module was identified as the significant module with AD and MetS. GO analysis of shared genes showed that intracellular transport and establishment of localization in cell and organelle organization were enriched in the pathophysiology of AD and MetS. By using RF and Lasso learning methods, we finally obtained eight diagnostic genes, namely ARHGAP4, SNRPG, UQCRB, PSMA3, DPM1, MED6, RPL36AL and RPS27A. Their AUC were all greater than 0.7. Higher immune cell infiltrations expressions were found in the two diseases and were positively linked to the characteristic genes. The scRNA-seq datasets finally obtained seven cell clusters. Seven major cell types including CD8 T cell, monocytes, T cells, NK cell, B cells, dendritic cells and macrophages were clustered according to immune cell markers. The ssGSEA revealed that immune-related gene (SNRPG) was significantly regulated in the glycolysis-metabolic pathway. We identified genes with common diagnostic effects on both MetS and AD, and found genes involved in multiple metabolic pathways associated with various immune cells.


Emerging molecular mechanisms that power and regulate the anastral mitotic spindle of flowering plants.
Flowering plants, lacking centrosomes as well as dynein, assemble their mitotic spindle via a pathway that is distinct visually and molecularly from that of animals and yeast. The molecular components underlying mitotic spindle assembly and function in plants are beginning to be discovered. Here, we review recent evidence suggesting the preprophase band in plants functions analogously to the centrosome in animals in establishing spindle bipolarity, and we review recent progress characterizing the roles of specific motor proteins in plant mitosis. Loss of function of certain minus-end-directed KIN-14 motor proteins causes a broadening of the spindle pole; whereas, loss of function of a KIN-5 causes the formation of monopolar spindles, resembling those formed when the homologous motor protein (e.g., Eg5) is knocked out in animal cells. We present a phylogeny of the kinesin-5 motor domain, which shows deep divergence among plant sequences, highlighting possibilities for specialization. Finally, we review information concerning the roles of selected structural proteins at mitosis as well as recent findings concerning regulation of M-phase in plants. Insight into the mitotic spindle will be obtained through continued comparison of mitotic mechanisms in a diversity of cells.


An overview of thyroid eye disease.
Thyroid eye disease (also known as Graves' ophthalmopathy) is a complex orbital inflammatory disease, which can be sight threatening, debilitating and disfiguring. This overview discusses the epidemiology, risk factors, pathogenesis, presentation, ophthalmic clinical features, investigations and treatment of thyroid eye disease.


Muscle quality as a complementary prognostic tool in conjunction with sarcopenia assessment in younger and older individuals.
This pilot study investigated differences in lean tissue mass, muscle strength, muscle quality (strength per unit of muscle mass; MQ), and functional performance in healthy younger and older individuals. The most robust predictors of appendicular lean mass (ALM) were then determined in each group. Fifty younger (18-45 years) and 50 older (60-80 years) participants completed tests of upper and lower body strength alongside body composition by dual-energy X-ray absorptiometry from which upper- and lower-body MQ were estimated. Available cut-points for older people were used to determine low upper-body MQ in both groups. Low lower-body MQ was determined as at least two standard deviations below the mean of the younger group. Functional performance was assessed by gait speed. Sarcopenia was identified using two established definitions. Upper and lower body strength, ALM, lower-body MQ and gait speed were significantly higher in the younger group (all p < 0.002). Sarcopenia was identified in 2-4% of the older group. Low upper-body MQ was evident in 32% and 42% of the younger and older group, respectively. Low lower-body MQ was observed in 4% of younger participants, and 50% of older participants. In both groups, the most robust predictors of ALM were upper and lower body strength (young R2 = 0.74, 0.82; older R2 = 0.68, 0.72). Low MQ despite low prevalence rates of sarcopenia in both groups suggests a need for age-specific MQ cut-points. Muscle quality assessments might be useful complementary prognostic tools alongside existing sarcopenia definitions.


Involvement of H2 S, NO and BDNF-TrkB signalling pathway in the protective effects of simvastatin against pentylenetetrazole-induced kindling and cognitive impairments in mice.
Cognitive dysfunction was observed in pentylenetetrazole (PTZ)-kindled mice. The potential effectiveness of simvastatin (SIM) on PTZ-induced kindling and cognitive impairments in mice was evaluated. The influence of SIM on hydrogen sulphide (H2 S), nitric oxide (NO), reactive aldehydes and brain-derived neurotrophic factor/tyrosine receptor kinase B (BDNF-TrkB) signalling was also investigated. Kindling and cognitive impairments in mice were induced by 12 ip injections of PTZ (35 mg/kg) once every alternate day. The levels of reactive aldehydes and nitrite were increased while H2 S was decreased in PTZ-treated mice. These results were accompanied by a reduction in the gene expression of aldehyde dehydrogenase 2, cystathionine β-synthase, BDNF and TrkB. In PTZ-kindled mice, a rise in brain inducible nitric oxide synthase protein expression associated with histopathological changes was observed. SIM administration (1, 5 and 10 mg/kg, daily orally) along with alternate day of PTZ (35 mg/kg) resulted in a decrease in PTZ-induced kindling with a dose-dependent improvement in cognitive function. SIM (10 mg/kg) prevented, to variable extent, the disturbances associated with PTZ-kindled mice with cortical, cerebellar and hippocampal structural improvement. These results suggested that SIM triggers multiple mechanisms that improve cognitive function in PTZ-kindled mice through modulation of oxidative stress, H2 S, NO and BDNF-TrkB signalling pathway.


The combined effect of cisplatin and furosemide on hearing function in guinea pigs.
The effect of the combined administration of cisplatin and furosemide on the electrophysiological hearing thresholds and endocochlear DC potential (EP) was studied in guinea pigs. A lack of interaction was found in animals given repeated intraperitoneal injections of a low dose of cisplatin with a pharmacological dose of furosemide. An ototoxic interaction occurred when a moderately high dose of cisplatin was administered intravenously at a time when the strial function was most affected by a very high dose of furosemide. The interaction was seen both as a decreased EP and a pronounced shift of auditory thresholds. It is concluded that the stria vascularis plays a role in the ototoxic mechanism of cisplatin.


Antiproliferative activity and mode of action analysis of novel amino and amido substituted phenantrene and naphtho[2,1-b]thiophene derivatives.
Herein we present and describe the design and synthesis of novel phenantrene derivatives substituted with either amino or amido side chains and their biological activity. Antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity against cancer cells in comparison with 5-fluorouracile. Among all tested compounds, some compounds substituted with cyano groups showed a pronounced and selective activity in the nanomolar range of inhibitory concentrations against HeLa and HepG2. The strongest selective activity against HeLa cells was observed for acrylonitriles 8 and 11 and their cyclic analogues 15 and 17 substituted with two cyano groups with a corresponding IC50 = 0.33, 0.21, 0.65 and 0.45 μM, respectively. Compounds 11 showed the most pronounced selectivity being almost non cytotoxic to normal fibroblasts. Additionally, mode of biological action analysis was performed in silico and in vitro by Western blot analysis of HIF-1-α relative expression for compounds 8 and 11.


A knowledge-based approach to improving and homogenizing intensity modulated radiation therapy planning quality among treatment centers: an example application to prostate cancer planning.
Intensity modulated radiation therapy (IMRT) treatment planning can have wide variation among different treatment centers. We propose a system to leverage the IMRT planning experience of larger institutions to automatically create high-quality plans for outside clinics. We explore feasibility by generating plans for patient datasets from an outside institution by adapting plans from our institution. A knowledge database was created from 132 IMRT treatment plans for prostate cancer at our institution. The outside institution, a community hospital, provided the datasets for 55 prostate cancer cases, including their original treatment plans. For each "query" case from the outside institution, a similar "match" case was identified in the knowledge database, and the match case's plan parameters were then adapted and optimized to the query case by use of a semiautomated approach that required no expert planning knowledge. The plans generated with this knowledge-based approach were compared with the original treatment plans at several dose cutpoints. Compared with the original plan, the knowledge-based plan had a significantly more homogeneous dose to the planning target volume and a significantly lower maximum dose. The volumes of the rectum, bladder, and femoral heads above all cutpoints were nominally lower for the knowledge-based plan; the reductions were significantly lower for the rectum. In 40% of cases, the knowledge-based plan had overall superior (lower) dose-volume histograms for rectum and bladder; in 54% of cases, the comparison was equivocal; in 6% of cases, the knowledge-based plan was inferior for both bladder and rectum. Knowledge-based planning was superior or equivalent to the original plan in 95% of cases. The knowledge-based approach shows promise for homogenizing plan quality by transferring planning expertise from more experienced to less experienced institutions.


Evaluation of aeration strategy in moving bed sequencing batch reactor performing simultaneous 4-chlorophenol and nitrogen removal.
The aeration strategy ranging from intermittent to continuous aeration in the REACT period of moving bed sequencing batch reactor (MBSBR) was evaluated for simultaneous removal of 4-chlorophenol (4-CP) and nitrogen. The results show that the removal rates of 4-CP and ammonium nitrogen (NH(4)(+)-N) increased with the increase of continuous aeration period. In the presence of 4-CP, NH(4)(+)-N removal was mainly by the assimilation process. The removal of NH(4)(+)-N to oxidized nitrogen via oxidation was only observed after 4-CP was completely degraded with sufficient aeration period provided indicating the inhibitory effect of 4-CP on nitrification. As the intermittent aeration strategy would lead to slower 4-CP degradation resulting in the delay of nitrification process, continuous aeration would be the preferred strategy in the simultaneous removal of 4-CP and nitrogen in the MBSBR system.


LDL-C-lowering therapy: current and future therapeutic targets.
Recent trials have emphasized that more intensive low-density lipoprotein cholesterol (LDL-C) lowering results in a further reduction in cardiovascular disease risk. Uptitration of statins has limited incremental LDL-C-lowering effects and leads to an increased incidence of side effects. Therefore, attention has shifted toward alternative LDL-C-lowering modalities. Several promising compounds have entered the clinical trial arena, although with mixed results. Acyl-coenzyme A: cholesterol O-acyltransferase (ACAT) inhibitors failed to show benefit. Microsomal triglyceride transfer protein and squalene synthase inhibitors, in spite of beneficial lipid profile changes, have shown adverse event profiles. In contrast, inhibitors of intestinal cholesterol absorption have shown LDL-C-lowering efficacy associated with few side effects. The inhibition of apolipoprotein B100 synthesis by antisense oligonucleotides has now been tested in phase 2 clinical trials, with promising results. Finally, compounds modifying protein convertase subtilisin/kexin type 9 levels are currently in the preclinical phase. In the present article, we discuss these LDL-C-lowering strategies.


Decreased activities of thiamine diphosphatase in frontal and temporal cortex in Alzheimer's disease.
Thiamine diphosphatase (TDPase) activity was measured using a colorimetric assay in frontal and temporal cortex obtained at autopsy from eight patients with neuropathologically confirmed Alzheimer's disease (AD) and from an equal number of control patients matched for age and autopsy delay interval, free from neurological or psychiatric disorders. TDPase activities were significantly reduced in frontal cortex (by 28%, P < 0.05) and temporal cortex (by 62%, P < 0.01) of AD patients. These findings add to a growing body of evidence of altered thiamine neurochemistry in AD. Given the previous reports of an association of TDPase with cholinergic nerve terminals, loss of TDPase activities could reflect loss of cholinergic neurons in frontal and temporal cortex in AD.


Dutch survey of congenital coronary artery fistulas in adults: coronary artery-left ventricular multiple micro-fistulas multi-center observational survey in the Netherlands.
Congenital coronary artery-left ventricular multiple micro-fistulas (CA-LVMMFs) in adults are rare anomalies. They may cause angina pectoris and myocardial infarction in association with normal coronary arteries. From the medical databases of a Dutch Survey of coronary artery fistulas in adult cardiology population (30,829 patients), we identified 20 patients with CA-LVMMFs out of 71 fistula-subjects between 1996 and 2003. Clinical files and individual coronary angiograms were reviewed and analysed. There were 13 females and 7 males with a mean age of 67.3 years (range 49-82). The main presenting symptoms were angina pectoris and dyspnea in 70% of the patients. The ECG showed pathologic changes in 75%. Exercise tolerance test and 201-thallium stress scintigraphy were positive for myocardial ischemia in 29% and 50%, respectively of the tested patients. In the absence of significant atherosclerotic coronary artery disease, ipsilateral to the fistulas, myocardial infarction was documented in 15% of the patients. Chest X-ray revealed cardiomegaly in 38% of the patients. Congestive heart failure was documented in 10% of the patients. Uni-, bi- and multilateral fistulas were present in 50%, 45% and 5%, respectively. The origin was the LCA in 71% and the RCA in 29% of the fistulas. The majority (97%) originated from the mid or distal segments of the coronary vessels. Among those patients, the coronary arterial tree had single, dual, and triple vessel disease in 25%, 15% and 5%, respectively. Angiographic anatomy precludes surgical intervention; they were all followed by conservative medical management. Coronary artery-left ventricular multiple micro-fistulas are found more often in female patients. Furthermore, they originated from the distal segment of the coronary arteries. Coronary artery-left ventricular multiple micro-fistulas, in the presence of normal coronary arterial tree, may often lead to angina pectoris and coronary insufficiency.


Recommendations for primary care physicians to improve HPV vaccination rates during clinical encounters.
The availability of the human papillomavirus (HPV) vaccine has positioned primary care physicians to play an active role in ensuring its successful implementation. However, physicians must be aware of common knowledge, attitudes, and belief barriers associated with HPV and the vaccine that are often encountered during clinical visits. This editorial provides primary care physicians an overview of these barriers and realistic recommendations utilizing the "5A's" - Awareness, Assess, Address, Acceptability, and Activate. This mnemonic can help facilitate a physician's systematic approach to increasing HPV vaccination rates during the clinical encounter.


Development of tolerance to clobazam in fully kindled rats: effects of intermittent flumazenil administration.
The effects of acute and chronic treatment with the 1,5-benzodiazepine, clobazam, were studied on fully kindled amygdaloid seizures in rats. After acute dosing, clobazam significantly reduced all parameters of kindled seizures (seizure severity, seizure duration, duration of amygdalar afterdischarges) at doses of 7.5 or 10 mg/kg i.p. 'Active' plasma concentrations of clobazam ranged between 300-800 ng/ml. The elimination half-life of clobazam in plasma was about 1 h. Only very low (10-75 ng/ml) levels of the major metabolite, N-desmethylclobazam, were detected in rats. Administration of N-desmethylclobazam indicated that plasma concentrations of at least 300 ng/ml were necessary for anticonvulsant effects. During chronic administration of clobazam, 10 mg/kg 3 times daily, marked tolerance developed to the anticonvulsant and adverse (ataxiogenic and sedative) effects of the benzodiazepine. The experiment was repeated using a different protocol with minimized environmental stimuli and no amygdala stimulation during chronic clobazam administration. The loss of effects on seizure severity and motor function was similar to the first chronic experiment, whereas the loss of effects on seizure and afterdischarge duration was less marked. This indicates that conditioning of 'learned tolerance' is partly involved in clobazam tolerance in kindled rats. Intermittent injection of the benzodiazepine receptor antagonist, flumazenil, 5 mg/kg i.p. every third day, did not alter the loss of pharmacodynamic effects during chronic treatment with clobazam, but seemed to prevent hyperexcitation and other abstinence symptoms in the withdrawal period. The data indicate that periodic injection of a benzodiazepine receptor antagonist does not represent a possible therapeutic approach for preventing the development of tolerance during long-term benzodiazepine exposure.


Combined Toll-like receptor agonists synergistically increase production of inflammatory cytokines in human neonatal dendritic cells.
Dendritic cells (DC) are thought to be responsible for the reduced ability of human newborns to induce protective T-helper 1 (Th1) immune responses. The key player in Th1 differentiation, interleukin-12 (IL-12), is primarily produced in response to Toll-like receptor (TLR) binding by adult DC but not by neonatal DC. The potential use of various TLR agonist combinations for initiating neonatal monocyte-derived DC to prime Th1 responses was investigated. Single TLR ligands induced maturation only in adult DC; neonatal DC matured with combined targeting of TLR3/TLR8 or TLR4/TLR8, based on the expression of maturation markers. Similarly, the synergistic effects of combined TLR ligands could also be shown with adult and neonatal cytokine production, but different expression patterns were noted. In particular, IL-12p70 was produced by neonatal DC exclusively after combined TLR stimulation. Surprisingly, it was found that supernatants of combined stimulated neonatal DC could induce interferon-gamma production in autologous naïve T cells. Moreover, this interferon-gamma secretion was blocked by anti-IL-12p70 antibodies and increased after addition of recombined IL-12. In conclusion, these findings underline the differences between adult and neonatal DC and might suggest new strategies for promoting newborn Th1 immunity in response to pathogens and vaccine antigens.


Supercritical fluid in deep subduction zones as revealed by multiphase fluid inclusions in an ultrahigh-pressure metamorphic vein.
Due to their low viscosity, high mobility, and high element contents, supercritical fluids are important agents in the cycling of elements. However, the chemical composition of supercritical fluids in natural rocks is poorly understood. Here, we investigate well-preserved primary multiphase fluid inclusions (MFIs) from an ultrahigh-pressure (UHP) metamorphic vein of the Bixiling eclogite in Dabieshan, China, thus providing direct evidence for the components of supercritical fluid occurring in a natural system. Via the 3D modeling of MFIs by Raman scanning, we quantitatively determined the major composition of the fluid trapped in the MFIs. Combined with the peak-metamorphic pressure-temperature conditions and the cooccurrence of coesite, rutile, and garnet, we suggest that the trapped fluids in the MFIs represent supercritical fluids in a deep subduction zone. The strong mobility of the supercritical fluids with respect to carbon and sulfur suggests that such fluids have profound effects on global carbon and sulfur cycling.


The Regulatory Pathway for Advanced Cell Therapy and Gene Therapy Products in Brazil: A Road to Be Built.
The regulation of cell therapy and gene therapy products is a major challenge for the Brazilian state. From a legal point of view, the legislative apparatus, including constitutional, prohibits the marketing and patent of human substances. From the point of view of the organization of the state bureaucracy, the responsibilities for the regulation of research and application of these technologies in humans may involve up to four different institutions. The National Agency for Health Surveillance (ANVISA) has been the protagonist in structuring the regulation of cell therapy and gene therapy in Brazil, and steps have been taken to ensure quality of these products. However, obstacles such as the commercialization of these therapies and the need to determine whether these products will be regulated following the assumptions adopted in Brazil for drugs and biological products or for human blood and tissues still remain.


An adolescent treated with rapid maxillary expansion presenting with strabismus: a case report.
Few in vivo studies have investigated the effect of maxillary expansion on strabismus; however, some in vitro studies hypothesized that changes in the palatal width obtained with rapid maxillary expansion appliances could involve other bone structures that contain blood vessels and nerves conveying to the orbital cavity. The present case report seems to support that hypothesis, even if no analysis of pathogenetic mechanisms could be drawn. We present the case of a 14-year-old Caucasian girl affected by strabismus and referred for the treatment of a class III malocclusion with transverse maxillary deficiency, which was corrected by the application of a rapid maxillary expansion appliance (Haas type). At 2 months follow-up, the patient, who had not undergone any ophthalmologic treatment, was submitted to an ophthalmologic examination that revealed a marked change in the vision defect, which slightly relapsed at 6 months. The results of our clinical evaluation showed a remarkable modification of the oculomotor system of our patient as an outcome of the rapid maxillary expansion.Further studies are needed to clarify these findings and to investigate the clinical implications of these observations.


Modified transscleral fixation technique for refixation of dislocated intraocular lenses.
To evaluate the results of transscleral fixation of dislocated posterior chamber intraocular lenses (PC IOLs) by externalizing the haptics through a clear corneal incision. Department of Ophthalmology, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran. This retrospective interventional case series comprised 21 eyes (21 patients) in which a dislocated posterior chamber IOL was transsclerally refixated using a small superior clear corneal incision for externalization of the haptics. The suture was tied to the externalized haptic, after which the tied haptic was placed back in the anterior chamber and dialed to externalize the second haptic. After the second externalized haptic was tied, the IOL was reimplanted in the ciliary sulcus. The minimum follow-up was 6 months. The mean follow-up was 42.7 months +/- 21 (SD). The difference between the mean best corrected visual acuity before IOL dislocation (0.34 +/- 0.21 logMAR) and the mean after IOL refixation (0.38 +/- 0.19 logMAR) was not statistically significant (P = .16, t test). During follow-up, the PC IOL remained well centered in all eyes and no tilt or dislocation was observed. Scleral fixation of dislocated PC IOLs using temporary haptic externalization through a clear corneal incision minimized the need for complicated intraocular maneuvers, had a low incidence of complications, and provided an easy and effective way to reposition dislocated PC IOLs.


Sclerodermiform linear atrophy after the use of intralesional steroids for periorbital hemangiomas: a review of complications.
A 1-year-old girl developed a linear atrophy 3 months after a second injection of intralesional steroids for a periorbital hemangioma, followed by spontaneous resolution of the atrophy within 13 months. Reported and potential complications of intralesional steroids for periorbital hemangiomas are reviewed.


Reference materials for MS-based untargeted metabolomics and lipidomics: a review by the metabolomics quality assurance and quality control consortium (mQACC).
The metabolomics quality assurance and quality control consortium (mQACC) is enabling the identification, development, prioritization, and promotion of suitable reference materials (RMs) to be used in quality assurance (QA) and quality control (QC) for untargeted metabolomics research. This review aims to highlight current RMs, and methodologies used within untargeted metabolomics and lipidomics communities to ensure standardization of results obtained from data analysis, interpretation and cross-study, and cross-laboratory comparisons. The essence of the aims is also applicable to other 'omics areas that generate high dimensional data. The potential for game-changing biochemical discoveries through mass spectrometry-based (MS) untargeted metabolomics and lipidomics are predicated on the evolution of more confident qualitative (and eventually quantitative) results from research laboratories. RMs are thus critical QC tools to be able to assure standardization, comparability, repeatability and reproducibility for untargeted data analysis, interpretation, to compare data within and across studies and across multiple laboratories. Standard operating procedures (SOPs) that promote, describe and exemplify the use of RMs will also improve QC for the metabolomics and lipidomics communities. The application of RMs described in this review may significantly improve data quality to support metabolomics and lipidomics research. The continued development and deployment of new RMs, together with interlaboratory studies and educational outreach and training, will further promote sound QA practices in the community.


Characterization of Enterobacter cloacae BAGM01 Producing a Thermostable and Alkaline-Tolerant Rhamnolipid Biosurfactant from the Gulf of Mexico.
The search for novel biosurfactants (Bs) requires the isolation of microorganisms from different environments. The Gulf of Mexico (GoM) is a geographical area active in the exploration and exploitation of hydrocarbons. Recent metagenomic and microbiologic studies in this area suggested a potential richness for novel Bs microbial producers. In this work, nineteen bacterial consortia from the GoM were isolated at different depths of the water column and marine sediments. Bs production from four bacterial consortia was detected by the CTAB test and their capacity to reduce surface tension (ST), emulsion index (EI24), and hemolytic activity. These bacterial consortia produced Bs in media supplemented with kerosene, diesel, or sucrose. Cultivable bacteria from these consortia were isolated and identified by bacterial polyphasic characterization. In some consortia, Enterobacter cloacae was the predominant specie. E. cloacae BAGM01 presented Bs activity in minimal medium and was selected to improve its Bs production using a Taguchi and Box-Behnken experimental design; this strain was able to grow and presented Bs activity at 35 g L-1 of NaCl. This Bs decreased ST to around 34.5 ± 0.56 mNm-1 and presented an EI24 of 71 ± 1.27%. Other properties of this Bs were thermal stability, stability in alkaline conditions, and stability at high salinity, conferring important and desirable characteristics in multiple industries. The analysis of the genome of E. cloacae BAGM01 showed the presence of rhlAB genes that have been reported in the synthesis of rhamnolipids, and alkAB genes that are related to the degradation of alkanes. The bioactive molecule was identified as a rhamnolipid after HPLC derivatization, 1H NMR, and UPLC-QTOF-MS analysis.


Post-intensive care syndrome one month after discharge in surviving critically ill COVID-19 patients.
Incidence of post-intensive care syndrome at one month after hospital discharge in surviving critically ill COVID 19 patients and to identify associated factors. Prospective cohort study. Two multipurpose critical care units of the Araba University Hospital. Patients admitted to critical care units for severe acute respiratory failure secondary to COVID 19. None. Demographic variables, length of stay, Charlson index, APACHE II, SOFA, days of mechanical ventilation, tracheotomy, delirium, tetraparesis of the critical patient, EuroQol 5D5L, Minimental Test. A deterioration in the EuroQol health index (HI) from 90.9±16.9 to 70.9±24.7 (p<0.001) was observed. The impairment of the five EuroQol domains is: mobility (46.1%), usual activities (44.7%), discomfort/pain (30.7%), psychological domain (27.3%) and self-care (20.3%). The 61.5% suffer a significant decrease in their health index. Multivariate analysis by logistic regression shows us that delirium (OR=3.01; 95%CI: 1.01-8.9; p=0.047) and tracheostomy (OR=2.37; 95%CI: 1.09-5.14; p=0.029) show association with drop in EuroQoL 5D5L SI. The area under the ROC curve of the model is 67.3%, with a confidence interval between 58% and 76%. The model is calibrated using the Hosmer-Lemeshow test (χ2=0.468; p=0.792). Only 1.2% of patients showed a score ≤ 24, clearly pathological, on the Folstein's Minimental Test. Delirium and need for tracheostomy are associated with post-intensive care syndrome assessed by EuroQol 5D5L.


Doughnut sign of hepatic alveolar echinococcosis on FDG PET/CT: Clinical case report.
A characteristic metabolic finding of hepatic alveolar echinococcosis (HAE) on positron emission tomography/computed tomography (PET/CT) correlates with morphologic features on CT and magnetic resonance imaging (MRI). A young man from an endemic area was admitted to our hospital due to right upper quadrant pain for 2 months. CT and MRI revealed a heterogeneous mass with calcification, consisting of central necrosis and peripheral solid inflammatory tissues. Accordingly, FDG PET/CT demonstrated a characteristic metabolic finding of doughnut sign. Combining the above characteristic imaging features with positive serologic findings, the patient was diagnosed as HAE. He then underwent extracorporeal hepatectomy and liver autotransplantation followed by medical treatment of benzimidazoles. He remained asymptomatic without evidence of recurrence at 2-year follow-up. The characteristic metabolic appearance of HAE on FDG PET/CT, correlated with its morphologic features of CT and MRI, may allow to make accurate diagnoses.


Society of Gynecologic Oncology Journal Club: Controversial conversations in gynecologic cancer - Navigating maintenance therapy for homologous recombinant proficient ovarian cancer.
The Society of Gynecologic Oncology (SGO) Journal Club is an open forum to review pertinent studies relevant to controversial topics in the management of gynecologic cancers. On August 3rd, 2022, SGO hosted a Journal Club focused on the role of maintenance therapy for homologous recombinant proficient (HRP) patients with ovarian cancer. Navigating optimal therapies has become more complex with the emergence of new clinical trial data and the evolving understanding of how to classify ovarian cancers as HRP. Our speakers, Drs. Susan Modesitt, Barbara Norquist and Rodney Rocconi presented Gynecologic Oncology Group (GOG) 218 (Burger et al., 2011), the VITAL Trial (Rocconi et al., 2021), and the PRIMA study (Gonzalez-Martin et al., 2019). We asked our experts to discuss their opinions and interpretations on the application of these data to current clinical practice. Poll questions were presented to the audience for a pre- and post-webinar comparison (Table 1). Results of the poll questions are shown in Table 1.


Time of night and first night effects on arousal response in healthy adults.
Several factors, such as homeostatic and circadian influences, may affect the density of cortical and subcortical arousals (AR). The purpose of this study was to examine the time-of-night and the first night effect on AR response. AR were classified into microarousals (MA), phases of transitory activation (PAT), delta (D-burst) and K-complex burst (K-burst). The AR density and duration was analyzed during two consecutive nights with the analysis of sleep stage and sleep cycle in thirty-six healthy subjects. D- and K-burst showed a trend toward progressive decline across sleep cycles (p<0.0001). While MA rate was unaffected throughout sleep cycles, PAT index increased across the night (p=0.002). The density and duration of each group of AR exhibited reproducibility without significant differences between nights. An individual inter-night variability in AR density was found independently of night and sleep structure. While homeostatic and circadian influences affect nighttime subcortical and MA responses, a wakefulness drive modulates the occurrence of AR with movements. Although the pattern of AR responses was highly reliable from the first to second night, the substantial inter-individual variability suggests the existence of an individual susceptibility. The first night effect on arousal response is affected by individual susceptibility and circadian and homeostatic influences.


The History of MDMA as an Underground Drug in the United States, 1960-1979.
MDMA (3,4-methylenedioxy-methylamphetamine, a.k.a. "ecstasy") was first synthesized in 1912 and resynthesized more than once for pharmaceutical reasons before it became a popular recreational drug. Partially based on previously overlooked U.S. government documentation, this article reconstructs the early history of MDMA as a recreational drug in the U.S. from 1960 to 1979. According to the literature, MDMA was introduced as a street drug at the end of the 1960s. The first forensic detection of MDMA "on the street" was reported in 1970 in Chicago. It appears that MDMA was first synthesized by underground chemists in search of "legal alternatives" for the closely related and highly sought-after drug MDA, which was scheduled under the Controlled Substances Act (CSA) in 1970. Until 1974, nearly all MDMA street samples seized came from the U.S. Midwest, the first "hot region" of MDMA use. In Canada, MDMA was first detected in 1974 and scheduled in 1976. From 1975 to 1979, MDMA was found in street samples in more than 10 U.S. states, the West Coast becoming the major "hot region" of MDMA use. Recreational use of MDMA spread across the U.S. in the early 1980s, and in 1985 it was scheduled under the CSA.


Aerobiology and the global transport of desert dust.
Desert winds aerosolize several billion tons of soil-derived dust each year, including concentrated seasonal pulses from Africa and Asia. These transoceanic and transcontinental dust events inject a large pulse of microorganisms and pollen into the atmosphere and could therefore have a role in transporting pathogens or expanding the biogeographical range of some organisms by facilitating long-distance dispersal events. As we discuss here, whether such dispersal events are occurring is only now beginning to be investigated. Huge dust events create an atmospheric bridge over land and sea, and the microbiota contained within them could impact downwind ecosystems. Such dispersal is of interest because of the possible health effects of allergens and pathogens that might be carried with the dust.


The effect of spinally administered WIN 55,212-2, a cannabinoid agonist, on thermal pain sensitivity in diabetic rats.
Diabetic neuropathy (DN) is a common complication of diabetes that leads to allodynia, impaired nerve conduction, and progressive sensory loss. The aim of this study was to observe the effect of a high-affinity cannabinoid receptors agonist, WIN 55,212-2, on thermal hyperalgesia, nerve conduction velocity and sciatic nerve histopathology in diabetic rats. Diabetes was induced in rats using a single dose of streptozotocin (45 mg/kg IP). Intrathecal (IT) administration of WIN55, 212-2 (1, 10, 100 µg/10 µl, IT), produced antinociceptive effects in the hot plate test and also improved nerve conduction velocity (100 µg/10 µl, IT) and sciatic nerve histology. These data show that cannabinoids have potent antinociceptive effects through direct actions in the spinal dorsal horn of nociceptive pathway. This suggests that intrathecally administered cannabinoids may offer hopeful strategies for the treatment of diabetic neuropathic pain.


Biodegradation of ornithine-containing polylysine hydrogels.
The degradation of the cross-linked cationic poly(amino acid)-glutaraldehyde (GA) hydrogels by two kinds of proteolytic enzymes, trypsin and Aspergillus Protease Type XXIII, and by seven species of soil filamentous fungi has been investigated using homo- and copolypeptides of lysine (Lys) and ornithine (Orn). Trypsin degraded the hydrogels prepared from poly(Lys) and copoly(Lys Orn)s but not poly(Orn), while Aspergillus protease degraded all of them. Degradation time of hydrogels by the two proteases became longer with increasing Orn content in the gel. Seven species of soil filamentous fungi were cultured with hydrogels on Czapeck medium to evaluate the degree of microbial degradation of the hydrogels, and the three species of the fungi, Aspergillus oryzae, Penicillium citrinum and Curvularia sp., were grown in culture with an accompanying degradation of the gel matrix, while the other four species, Mucor sp., Rhizopus sp., Cladosporium sp., and Trichoderma sp., were not. The degree of degradation of gel matrix with growth of the three fungi became lower with increasing Orn content in the gel matrix. The results might offer some clues to the applications for the controlled biodegradation of cationic poly(amino acid) hydrogel by introduction of Orn, suggesting that unnatural amino acid resists hydrolysis by proteases or microorganisms.


Environmental specimen banking and poisons control--a new challenge.
Today clinical toxicology and poisons control are widely lacking objective criteria, e.g., analytical data, figures of kinetics and metabolism in acute and chronic poisoning. Co-operation between clinical toxicology and an environmental specimen bank for human tissue will help to overcome many difficulties and complement one another. The possible power of such a co-operation is demonstrated by the example of the institutions in Münster, Germany. The successful strategies used for setting-up an environmental specimen bank for human tissue may also be applied in clinical toxicology and experimental toxicology. The frame of a university medical clinic seems to be the ideal basis of an effective co-operation of an Environmental Specimen Bank for Human Tissue, a Poisons Control Centre and clinical toxicology. In general a co-operation of an environmental specimen bank for human tissue and a poisons control centre will be cost-saving and beneficial to both and an environmental specimen bank for human tissue will gain the status of a unique tool for risk assessment of xenobiotics.


Subsensitivity of P2X but not vanilloid 1 receptors in dorsal root ganglia of rats caused by cyclophosphamide cystitis.
The application of cyclophosphamide to rats was used to induce interstitial cystitis. Behavioural studies indicated a strong pain reaction that developed within 2 h and levelled off thereafter causing a constant pain during the following 18 h. Neurons prepared from L6/S1 dorsal root ganglia innervating the urinary bladder responded to the application of capsaicin or alpha,beta-methylene ATP (alpha,beta-meATP) with an increase of intracellular Ca2+ ([Ca2+]i). The [Ca2+]i responses to capsaicin were identical in the dorsal root ganglion cells of cyclophosphamide- and saline-treated rats, whereas alpha,beta-meATP induced less increase in [Ca2+]i in the cyclophosphamide-treated animals than in their saline-treated counterparts. Hence, alpha,beta-meATP-sensitive P2X3 and/or P2X2/3 receptors of L6/S1 dorsal root ganglion neurons were functionally downregulated during subacute pain caused by experimental cystitis. In contrast, capsaicin-sensitive vanilloid 1 receptors did not react to the same procedure. Thoracal dorsal root ganglia, not innervating the urinary bladder, were also unaltered in their responsiveness to alpha,beta-meATP by cyclophosphamide treatment.


Fungus-Based MnO/Porous Carbon Nanohybrid as Efficient Laccase Mimic for Oxygen Reduction Catalysis and Hydroquinone Detection.
Developing efficient laccase-mimicking nanozymes via a facile and sustainable strategy is intriguing in environmental sensing and fuel cells. In our work, a MnO/porous carbon (MnO/PC) nanohybrid based on fungus was synthesized via a facile carbonization route. The nanohybrid was found to possess excellent laccase-mimicking activity using 2,2'-azinobis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) as the substrate. Compared with the natural laccase and reported nanozymes, the MnO/PC nanozyme had much lower Km value. Furthermore, the electrochemical results show that the MnO/PC nanozyme had high electrocatalytic activity toward the oxygen reduction reaction (ORR) when it was modified on the electrode. The hybrid nanozyme could catalyze the four-electron ORR, similar to natural laccase. Moreover, hydroquinone (HQ) induced the reduction of oxABTS and caused the green color to fade, which provided colorimetric detection of HQ. A desirable linear relationship (0-50 μM) and detection limit (0.5 μM) were obtained. Our work opens a simple and sustainable avenue to develop a carbon-metal hybrid nanozyme in environment and energy applications.


Influence of Intensity-Modulated Radiation Therapy on the Life Quality of Patients with Nasopharyngeal Carcinoma.
The present study intends to explore the influence of intensity-modulated radiation therapy on the quality of life for patients with nasopharyngeal carcinoma, which provides a theoretical basis and practical foundation for clinical practice. The present study randomly enrolled 130 cases of patients with nasopharyngeal carcinoma (NPC) in different stages who were admitted in The Second Affiliated Hospital of Fujian Medical University and the First Affiliated Hospital of Chongqing Medical University from September 2007 to August 2012, including 65 cases in IMRT group who received intensity-modulated radiation therapy and 65 cases in CRT group who received conventional radiation therapy. The prescribed dose in the target region of radical radiation therapy was 72 Gy/36 f; the prescribed dose in the target region at high risk was 60-64 Gy/30-32 f; the prescribed dose in the target region at low risk was 50-54 Gy/25-27 f and 2 Gy/f, with conventional fractionated irradiation of 1 f/d and 5 f/w. The data of the quality of life for patients with NPC who received intensity-modulated radiation therapy and conventional radiation therapy were collected and analyzed by filling in the questionnaire survey, including the Quality of Life Questionnaire of Head and Neck 35 (QLQ-H&N35) and Shot Form 36 Health Survey Questionnaire (SF-36). RP, VT, BP, SF, and RE scores in eight fields in SF-36 Scale were declined during the radiation therapy and risen again after radiation therapy, and those measured at 6 months after radiation therapy were higher than those before radiation therapy (all P < 0.05). The scores in IMRT group measured at two and six months after radiation therapy were all higher than those in CRT group (all P < 0.05). The scores of head and neck pain, pararthria, dysphagia, social difficulty, sensory difficulty, difficulty in feeding, xerostomia, cough, sticky saliva, and sensory discomfort during the radiation therapy were lower than those before radiation therapy (all P < 0.05). Except for the scores of sticky saliva and xerostomia, the other scores measured at 6 months after radiation therapy were all lower than those before radiation therapy, and the scores of dysphagia, sticky saliva, and xerostomia in MRT group were lower than those in CRT group (all P < 0.05). Conventional radiation therapy and intensity-modulated radiation therapy can cause a decline the quality of life for the patient with head and neck cancer, but intensity-modulated radiation therapy can improve local tumor control rate and significantly reduce the incidence of adverse reactions.


Proliferation of human Schwann cells induced by neu differentiation factor isoforms.
Neu differentiation factor (NDF), a 44-kD polypeptide, is a member of the neuregulin family which also includes glial growth factor, heregulin and acetylcholine-receptor-inducing activity. Previous studies have demonstrated that NDF/glial growth factor/heregulin/acetylcholine-receptor-including activity are products of neurons and mediate proliferation, differentiation and gene expression in Schwann cells of experimental animals. In the present study, the efficacy of different isoforms of NDF in stimulating human Schwann cell proliferation is investigated in Schwann-cell-enriched cultures derived from fetal human dorsal root ganglia (15-20 weeks gestation). NDF isoforms examined include alpha1, alpha2, EGF-like domain alpha2 (EGFalpha2), alpha3, beta1, EGFbeta1, EGFbeta, beta2 and beta3. For the assessment of Schwann cell proliferation, double immunostaining using antibodies specific for S-100 protein and bromodeoxyuridine was used. While treatment of Schwann cells with NDF alpha isoforms (alpha1, alpha2, alpha3 and EGFalpha2) had little effect on Schwann cell proliferation, NDF beta isoforms (beta1, beta2, beta3, EGFbeta1 and EGFbeta) induced a greatly enhanced proliferation in Schwann cells. The proliferation index in unstimulated Schwann cells was 1.3 +/- 0.9%, whereas in Schwann cells treated with NDFbeta isoforms the proliferation index was 21.8 +/- 2.2%. The finding that the truncated beta isoforms such as EGFbeta1 and EGFbeta retain a mitogenic activity as potent as full-length beta isoform indicates that the C-terminal portion of the EGF-like domain is responsible for its receptor binding and subsequent biological activity.


Spectrophotometric assay for ornithine decarboxylase.
A rapid and sensitive spectrophotometric assay for ornithine decarboxylase is described. It is based on the observation that the product of ornithine decarboxylase, putrescine, reacts with 2,4,6-trinitrobenzenesulfonic acid to give a colored product soluble in 1-pentanol whereas ornithine does not. The amount of putrescine produced by the enzyme was determined by measuring the absorbance of the 1-pentanol extract of the reaction mixture at 420 nm, and by comparing the results to those obtained by the trapping of 14CO2 and by HPLC assays. The three assays were found to be equivalent in sensitivity, with the spectrophotometric assay having the advantages of being relatively rapid, requiring only common laboratory equipment, and not requiring the use of radioactive isotopes.


Spatial Relationship Between the Metanephros and Adjacent Organs According to the Carnegie Stage of Development.
The morphological changes in the metanephros and its spatial relationship to the adjacent organs was evaluated based on the Carnegie stages (CSs) from 14 through 23. The imaging modalities used included magnetic resonance imaging (N = 4), phase-contrast X-ray computed tomography (N = 11), and serial histological sections (N = 40), supplemented by three-dimensional image reconstruction. The orientation of the hilus of the metanephros changed significantly between CS17 (34.4 ± 13.7 degrees) and 18 (122.3 ± 38.1 degrees), with an increase in the number of branches of the urinary collecting system, from 1.61 ± 0.42 at CS17 to 3.20 ± 0.35 at CS18. This increase in the number of branches influenced the growth of the metanephros and the orientation of its hilus. The right and left metanephroses were in proximity throughout the embryonic period. The local maximum interpole distances were observed at CS18 (0.87 ± 0.11 mm for the upper and 0.50 ± 0.25 mm for the lower pole). Mesenchymal tissue was observed between the metanephros and iliac arteries, as well as between the right and left metanephros. Throughout development, the position of the lower pole of the metanephros remained adjacent to the aortic bifurcation. The position of the upper pole, referenced with respect to the aortic bifurcation, increased by >2.0 mm, reflecting the longitudinal growth of the metanephros. Our findings provide a detailed description of the morphogenesis of the metanephros and of its hilus, which might contribute to our understanding of congenital malformations and malpositions of the kidneys. Anat Rec, 302:1901-1915, 2019. © 2019 American Association for Anatomy.


Mitochondrial calcium uniporter blocker effectively prevents brain mitochondrial dysfunction caused by iron overload.
Although iron overload induces oxidative stress and brain mitochondrial dysfunction, and is associated with neurodegenerative diseases, brain mitochondrial iron uptake has not been investigated. We determined the role of mitochondrial calcium uniporter (MCU) in brain mitochondria as a major route for iron entry. We hypothesized that iron overload causes brain mitochondrial dysfunction, and that the MCU blocker prevents iron entry into mitochondria, thus attenuating mitochondrial dysfunction. Isolated brain mitochondria from male Wistar rats were used. Iron (Fe(2+) and Fe(3+)) at 0-286 μM were applied onto mitochondria at various incubation times (5-30 min), and the mitochondrial function was determined. Effects of MCU blocker (Ru-360) and iron chelator were studied. Both Fe(2+) and Fe(3+) entered brain mitochondria and caused mitochondrial swelling in a dose- and time-dependent manner, and caused mitochondrial depolarization and increased ROS production. However, Fe(2+) caused more severe mitochondrial dysfunction than Fe(3+). Although all drugs attenuated mitochondrial dysfunction caused by iron overload, only an MCU blocker could completely prevent ROS production and mitochondrial depolarization. Our findings indicated that iron overload caused brain mitochondrial dysfunction, and that an MCU blocker effectively prevented this impairment, suggesting that MCU could be the major portal for brain mitochondrial iron uptake.


Doppler ultrasound evaluation of extracranial cerebrovascular disease.
Carotid Doppler examination was compared with arteriographic findings in 125 patients. The results demonstrated exact correlation in 87% of vessels studied. Clinically significant errors occurred at a rate of 4.5%. Clinically insignificant errors (8.5%) were usually the result of wall disease being mistaken for nonhemodynamically significant stenosis.


Comparative analysis of the effects of OLIF and TLIF on adjacent segments after treatment of L4 degenerative lumbar spondylolisthesis.
The fusion of the lumbar spine may lead to the degeneration of the adjacent segments. In this study, the effects of OLIF and TLIF on adjacent segments after treatment of L4 degenerative lumbar spondylolisthesis (DLS) were compared and analysed. This was a retrospective analysis of the medical records of consecutive patients treated with OLIF or TLIF for L4DLS. They were divided into the OLIF group and TLIF group based on different treatment methods. Cage height, segmental lordosis (SL), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were compared between the two groups, and the postoperative biomechanical changes were analysed by establishing the disc angle (DA). The clinical outcomes were analysed by comparing the visual analogue scale (VAS), Oswestry Disability Index (ODI) and incidence of adjacent segment disease (ASDis) between the two groups. The intervertebral disc height (IDH), intervertebral foramen height (IDH), intervertebral foramen area (IFA), sliding distance (SD), and angular displacement (AD) in L3-4 and L5-S1 were compared between the two groups. The incidence of aggravated disc degeneration (ADD), the incidence of aggravated zygapophyseal joint degeneration (AJD) and the incidence of adjacent segment degeneration (ASDeg) were compared between the two groups for radiological degeneration. At the last follow-up, there was one case of ASDis in the OLIF group (2.78%) and two cases in the TLIF group (5.56%). At the last follow-up, compared with the preoperative values, IDH, IFH, and IFA of the adjacent segments above and below L4-5 decreased in both groups (P < 0.05); the SD and AD increased in both groups (P < 0.05). The cage height and L4-5 IDH in the OLIF group were significantly higher than those in the TLIF group (P < 0.05). SL, LL, PT, SS, and L5- S1DA were significantly improved in the OLIF group compared with the TLIF group (P < 0.05). The incidence of L3-4ASDeg in the two groups was higher than that of L5-S1. The incidence of ASDeg and the incidence of L5-S1ADD in the OLIF group were lower than those in the TLIF group, but the incidence of L5-S1AJD was higher than that in the TLIF group. L4DLS after OLIF and TLIF treatment will cause adjacent segment degeneration, and L3-4 degeneration is more obvious than L5-S1 degeneration. OLIF has more advantages in restoring lumbar sagittal balance. Compared with TLIF, OLIF can weaken the degeneration of the L5-S1 disc and increase the degeneration of the L5-S1 zygapophyseal joints.


Femtosecond covariance spectroscopy.
The success of nonlinear optics relies largely on pulse-to-pulse consistency. In contrast, covariance-based techniques used in photoionization electron spectroscopy and mass spectrometry have shown that a wealth of information can be extracted from noise that is lost when averaging multiple measurements. Here, we apply covariance-based detection to nonlinear optical spectroscopy, and show that noise in a femtosecond laser is not necessarily a liability to be mitigated, but can act as a unique and powerful asset. As a proof of principle we apply this approach to the process of stimulated Raman scattering in α-quartz. Our results demonstrate how nonlinear processes in the sample can encode correlations between the spectral components of ultrashort pulses with uncorrelated stochastic fluctuations. This in turn provides richer information compared with the standard nonlinear optics techniques that are based on averages over many repetitions with well-behaved laser pulses. These proof-of-principle results suggest that covariance-based nonlinear spectroscopy will improve the applicability of fs nonlinear spectroscopy in wavelength ranges where stable, transform-limited pulses are not available, such as X-ray free-electron lasers which naturally have spectrally noisy pulses ideally suited for this approach.


The neonatal recognition of partial 11q trisomy (previously 'trisomy 22').
The recognition of chromosomal abnormalities in the neonatal period is important. Paediatricians should be aware that the partial 'Trisomy 22' (now partial 11q trisomy) syndrome has a recognizable phenotypic expression and is relatively common. The distinctive facies with a long philtrum, micrognathia, beaked nose and cleft palate, associated with hypotonia and other congenital abnormalities, should make early postnatal diagnosis possible so that parental counselling can be given without delay.


Zirconium-modified biochar as the efficient adsorbent for low-concentration phosphate: performance and mechanism.
Achieving advanced treatment of phosphorus (P) to prevent water eutrophication and meet increasingly stringent wastewater discharge standard is an important goal of water management. In this study, a low-cost, high-efficiency phosphate adsorbent zirconium-modified biochar (ZrBC) was successfully synthesized through co-precipitation method, in which the biochar was prepared from the pyrolysis of peanut shell powder. ZrBC exhibited strong adsorption ability to low-concentration phosphate (< 1 mg·L-1) in water, and the phosphate removal reached 100% at the investigated dosage range (0.1-1.0 mg·L-1). The adsorption process could be described well by pseudo-second-order model and Langmuir isotherm model, indicating that the phosphate adsorption by ZrBC was mainly a chemical adsorption and single-layer adsorption process. The calculated static maximum phosphate adsorption capacity was 58.93 mg·g-1 at 25 °C. The ligand exchange between surface hydroxyl groups and phosphate was the main mechanism for the phosphate adsorption on ZrBC. The presence of coexisting anions except for SO42- had little effect on the phosphate removal. At the column experiment, ZrBC showed superior treatment capacities for simulated secondary effluents and the breakthrough time for 0.5 mg·L-1 effluent phosphate concentration reached 190 h. ZrBC highlights the potential as an effective and environment-friendly adsorbent for the removal of low-concentration phosphate from secondary effluents of municipal wastewater treatment plants (WWTPs).


Acute epidermal necrolysis or Lyell syndrome.
Acute epidermal necrolysis may be caused by staphylococcal toxins (staphylococcal scalded skin syndrome and toxic shock syndrome) or may be related to usually drug-induced hyper-sensitivity mechanisms (toxic epidermal necrolysis). Diagnostic certainty can only be obtained by histologic localisation of a cleavage plane which is intraepidermal in staphylococcal scalded skin syndrome but situated at the dermo-epidermal junction in toxic epidermal necrolysis. Steroid therapy is indicated in toxic epidermal syndrome. This report of two cases of acute epidermal necrolysis emphasizes the importance of an early skin biopsy for accurate diagnosis and appropriate treatment.


Acetylmethylcarbinol production and the classification of aeromonads associated with ulcerative diseases of ectothermic vertebrates.
Page, L. A. (Biological Research Institute, San Diego, and University of California, Davis). Acetylmethylcarbinol production and the classification of aeromonads associated with ulcerative diseases of ectothermic vertebrates. J. Bacteriol. 84:772-777. 1962.-Quantitative colorimetric tests were made for acetylmethylcarbinol (AMC) production by 14 Aeromonas isolates from ulcerous lesions of snakes, lizards, frogs, and other animals, and by 27 cultures of "identified" aeromonads. The tests revealed that: (i) some strains failed to produce AMC, while the other strains produced AMC in amounts of 5 to > 100 mug/ml of culture; (ii) the reagents employed in the standard method of Barritt failed to detect AMC in concentrations below 35 mug/ml; and (iii) certain strains reported as producing AMC at 23 C and not at 37 C (or vice versa) produced AMC at both temperatures, but at one temperature produced AMC at a level below the sensitivity of the qualitative test. The strains representing the two biotypes could not be distinguished on the basis of their morphology, habitat, pathogenicity for mice or snakes, or serological specificity. Therefore, the Aeromonas classification proposed by Ewing, Hugh, and Johnson, who incorporated the two biotypes into one species, was followed, and the new isolates were designated A. hydrophila.


Neonatal radiofrequency catheter ablation of junctional tachycardias.
Junctional tachycardias comprise several arrhythmia types with differing mechanisms, principally involving the region of the atrioventricular (A-V) junction. Neonatal radiofrequency catheter ablation has typically been reserved for life-threatening, drug-refractory cases due to the unique concerns regarding patient size and development. We performed radiofrequency catheter ablation on two neonates with incessant, rapid junctional tachycardias and hemodynamic compromise after failing conventional medical therapy. This report describes 2 neonates who underwent emergent radiofrequency catheter ablation, and compares these two patients to a larger pediatric catheter ablation patient cohort. Both neonates had an acutely successful outcome and were able to be discharged within a week of the ablation procedure. Fluoroscopy time and total procedure time were shorter in these two patients than in the course of the average pediatric catheter ablation. Though long-term developmental consequences of neonatal catheter ablation are yet unknown, in unique extreme situations, radiofrequency catheter ablation can be performed in neonates, as in older children and adults, without excessive acute morbidity.