Comprehensive analysis of the mutation spectrum in 301 German ALS families.

Abstract:
OBJECTIVES
Recent advances in amyotrophic lateral sclerosis (ALS) genetics have revealed that mutations in any of more than 25 genes can cause ALS, mostly as an autosomal-dominant Mendelian trait. Detailed knowledge about the genetic architecture of ALS in a specific population will be important for genetic counselling but also for genotype-specific therapeutic interventions.

METHODS
Here we combined fragment length analysis, repeat-primed PCR, Southern blotting, Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of genetic variants in ALS disease genes in 301 German pedigrees with familial ALS. We report C9orf72 mutations as well as variants in consensus splice sites and non-synonymous variants in protein-coding regions of ALS genes. We furthermore estimate their pathogenicity by taking into account type and frequency of the respective variant as well as segregation within the families.

RESULTS
49% of our German ALS families carried a likely pathogenic variant in at least one of the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1, whereas the relative contribution of the other ALS genes in this familial ALS cohort was 4%. We identified several previously unreported rare variants and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes.

CONCLUSIONS
We here present a comprehensive genetic characterisation of German familial ALS. The present findings are of importance for genetic counselling in clinical practice, for molecular research and for the design of diagnostic gene panels or genotype-specific therapeutic interventions in Europe.

Müller|Kathrin|K|
Brenner|David|D|
Weydt|Patrick|P|
Meyer|Thomas|T|
Grehl|Torsten|T|
Petri|Susanne|S|
Grosskreutz|Julian|J|
Schuster|Joachim|J|
Volk|Alexander E|AE|
Borck|Guntram|G|
Kubisch|Christian|C|
Klopstock|Thomas|T|
Zeller|Daniel|D|
Jablonka|Sibylle|S|
Sendtner|Michael|M|
Klebe|Stephan|S|
Knehr|Antje|A|
Günther|Kornelia|K|
Weis|Joachim|J|
Claeys|Kristl G|KG|
Schrank|Berthold|B|
Sperfeld|Anne-Dorte|AD|
Hübers|Annemarie|A|
Otto|Markus|M|
Dorst|Johannes|J|
Meitinger|Thomas|T|
Strom|Tim M|TM|
Andersen|Peter M|PM|
Ludolph|Albert C|AC|
Weishaupt|Jochen H|JH|
|||

D020022:Genetic Predisposition to Disease

amyotrophic lateral sclerosis
genetics
whole exome sequencing


Study of luminescence properties of dysprosium-doped CaAl12 O19 phosphor for white light-emitting diodes.

Abstract: Dy3+ -doped CaAl12 O19 phosphors were synthesized utilizing a combustion method. Crystal structure and morphological examinations were performed respectively using X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques to identify the phase and morphology of the synthesized samples. Fourier transform infrared spectroscopy (FTIR) estimations were carried out using the KBr method. Photoluminescence properties (excitation and emission) were recorded at room temperature. CaAl12 O19 :Dy3+ phosphor showed two emission peaks respectively under a 350-nm excitation wavelength, centered at 477 nm and 573 nm. Dipole-dipole interaction via nonradiative energy shifting has been considered as the major cause of concentration quenching when Dy3+ concentration was more than 3 mol%. The CIE chromaticity coordinates positioned at (0.3185, 0.3580) for the CaAl12 O19 :0.03Dy3+ phosphor had a correlated color temperature (CCT) of 6057 K, which is situated in the cool white area. Existing results point out that the CaAl12 O19 :0.03Dy3+ phosphor could be a favorable candidate for use in white light-emitting diodes (WLEDs).

photoluminescence
concentration quenching
WLEDs
Dy3 +
aluminate


Restoring lumbar lordosis: a systematic review of controlled trials utilizing Chiropractic Bio Physics® (CBP®) non-surgical approach to increasing lumbar lordosis in the treatment of low back disorders.

Abstract: [Purpose] To systematically review controlled trial evidence for the use of lumbar extension traction by Chiropractic BioPhysics® methods for the purpose of increasing lumbar lordosis in those with hypolordosis and low back disorders. [Methods] Literature searches were performed in Pubmed, PEDro, CINAHL, Cochrane, and ICL databases. Search terms included iterations related to the lumbar spine, low back pain and extension traction rehabilitation. [Results] Four articles detailing 2 randomized and 1 non-randomized trial were located. Trials demonstrated increases in radiographic measured lordosis of 7-11°, over 10-12 weeks, after 30-36 treatment sessions. Randomized trials demonstrated traction treated groups mostly maintained lordosis correction, pain relief, and disability after 6-months follow-up. The non-randomized trial showed lordosis and pain intensity were maintained with periodic maintenance care for 1.5 years. Importantly, control/comparison groups had no increase in lumbar lordosis. Randomized trials showed comparison groups receiving physiotherapy-less the traction, had temporary pain reduction during treatment that regressed towards baseline levels as early as 3-months after treatment. [Conclusion] Limited but good quality evidence substantiates that the use of extension traction methods in rehabilitation programs definitively increases lumbar hypolordosis. Preliminarily, these studies indicate these methods provide longer-term relief to patients with low back disorders versus conventional rehabilitation approaches tested.

Oakley|Paul A|PA|
Ehsani|Niousha Navid|NN|
Moustafa|Ibrahim M|IM|
Harrison|Deed E|DE|

Lumbar lordosis
Low back pain
Spine traction


Are Eating Disorders Risk Factors for Type 2 Diabetes? A Systematic Review and Meta-analysis.

Abstract:
RECENT FINDINGS
Eating disorders (ED) affect energy intake modifying body fat depots. Prior evidence suggests that binge eating disorder (BED) and bulimia nervosa (BN) could increase the risk for type 2 diabetes (T2D), while anorexia nervosa (AN) could reduce it.

PURPOSE OF REVIEW
A systematic review and meta-analysis were conducted to evaluate if ED are risk factors for T2D. Ten studies were selected out of 1057 screened. Meta-analysis of six studies with T2D as outcome is reported. Among cross-sectional studies, both BED (OR 3.69, 95% CI [1.12-12.12]) and BN (OR 3.45 [1.92-6.1]) increased the risk of T2D, while AN was not associated with lower risk (OR 0.87 [0.40-1.88]). Cohort studies showed increased risk of T2D with BN (RR 1.7 [1.2-2.5]), and decreased risk with AN (RR 0.71 [0.52-0.98]), but for BED the association was less clear (OR 3.34 [0.85-13.12]). Limitations of studies and recommendations for future research are presented.

Nieto-Martínez|Ramfis|R|
González-Rivas|Juan P|JP|
Medina-Inojosa|José R|JR|
Florez|Hermes|H|

D003430:Cross-Sectional Studies
D003924:Diabetes Mellitus, Type 2
D001068:Feeding and Eating Disorders
D005260:Female
D006801:Humans
D012307:Risk Factors

Eating disorders
Binge eating disorder
Bulimia nervosa
Anorexia nervosa
Diabetes mellitus type 2
Night eating syndrome


Molecular Mechanisms of Sexually Dimorphic Nervous System Patterning in Flies and Worms.

Abstract: Male and female brains display anatomical and functional differences. Such differences are observed in species across the animal kingdom, including humans, but have been particularly well-studied in two classic animal model systems, the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans. Here we summarize recent advances in understanding how the worm and fly brain acquire sexually dimorphic features during development. We highlight the advantages of each system, illustrating how the precise anatomical delineation of sexual dimorphisms in worms has enabled recent analysis into how these dimorphisms become specified during development, and how focusing on sexually dimorphic neurons in the fly has enabled an increasingly detailed understanding of sex-specific behaviors.

sexual dimorphisms
Drosophila
Caenorhabditis elegans
behavior
differentiation


Blunt Craniofacial Trauma as a Manifestation of Excited Delirium Caused by New Psychoactive Substances.

Abstract: The body of a 19-year-old male was found apparently concealed underneath bushes with recent head and facial trauma, and multiple superficial abrasions. Subsequently, it was discovered that the decedent had been running into objects and buildings following the ingestion the evening before of what was thought to be lysergic acid diethylamide (LSD). Blood staining of a nearby wall close to where the body was lying was in keeping with the described behavior. Toxicology revealed 3,4-methylenedioxymethamphetamine (Ecstasy), in addition to two only recently available drugs 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, (25B-NBOMe), and 1-(3,4-methylenedioxyphenyl)-2-(1-pyrrolidinyl)-1-butanone, (MDPBP). At autopsy, the skull was fractured with cerebral swelling, contusions, and subarachnoid hemorrhage. Death was due to blunt cranial trauma against a background of mixed drug toxicity. The case demonstrates a rare cause of death in a drug-induced acute delirium, as well as highlighting two new designer street drugs that may result in significant aberrant behavior.

Byard|Roger W|RW|
Cox|Matthew|M|
Stockham|Peter|P|


Use of Butorphanol as Treatment for Cholestatic Itch.

Abstract:
BACKGROUND
Pruritus is a debilitating symptom of cholestatic diseases such as primary biliary cholangitis and primary sclerosing cholangitis and often results in major reduction in quality of life for afflicted patients. Classic treatment options for the treatment of cholestatic pruritus include antihistamines, bile acid resins, serotonin reuptake inhibitors, and mu-opioid antagonists. Unfortunately, these drugs are not always successful in treating pruritus of cholestasis and may be associated with adverse effects. Recent advances in our understanding of itch pathophysiology have led to the use of butorphanol, a kappa-opioid agonist and mu-opioid antagonist, for the treatment of various forms of pruritus. Reports of butorphanol to treat cholestatic itch specifically are rare.

AIMS
To better understand the role of butorphanol in the treatment of cholestatic pruritus, including characterization of its side effect profile.

METHODS
We present a case series of eight adult patients with cholestatic disease who were treated with butorphanol in hopes of alleviating intractable pruritus. Patients were identified through a clinical data request form serviced by University of Miami Information Technology.

RESULTS
Five out of eight patients (62.5%) reported successful reductions in itch severity after treatment with butorphanol, two patients reported no (or transient) change in itch severity, and one patient reported a paradoxical increase in itching. Side effects included somnolence, sedation, nausea, vomiting, and dizziness.

CONCLUSIONS
Butorphanol was safe and leads to clinically significant symptomatic improvement. Clinicians should be aware of butorphanol as an off-label treatment option for pruritus of cholestasis. Further studies are needed to better characterize the effect of butorphanol on cholestatic itch.

Golpanian|Rachel Shireen|RS|
Yosipovitch|Gil|G|
Levy|Cynthia|C|

Butorphanol
Treatment
Pruritus
Primary biliary cholangitis
Primary sclerosing cholangitis
Cholestasis


Listening to motivational music while walking elicits more positive affective response in patients with cystic fibrosis.

Abstract:
OBJECTIVE
The purpose of this study was to investigate the effects of motivational and relaxation music on affective responses during exercise in patients with cystic fibrosis (CF).

METHODS
Thirty-seven patients with CF performed the 6-min walk test (6MWT) under three experimental conditions: listening to no music, relaxation music, and motivational music. 6-min distance × body weight product (6MWORK) was calculated for each trial. Patients' affective responses during exercise was evaluated with Feeling Scale (FS). The motivational qualities of music were evaluated with the Brunel Music Rating Inventory-2 (BMRI-2).

RESULTS
6MWORK was significantly lower while listening to relaxation music compared to 6MWORK without music (p < 0.05). FS and BMRI-2 scores were significantly higher during 6MWT with motivational music than 6MWT with relaxation music (p < 0.05).

CONCLUSIONS
Carefully selected motivational music can lead to positive affective response during exercise and increase the enjoyment of patients from exercises in CF.

Calik-Kutukcu|Ebru|E| Saglam|Melda|M| Vardar-Yagli|Naciye|N| Cakmak|Aslihan|A| Inal-Ince|Deniz|D| Bozdemir-Ozel|Cemile|C| Sonbahar-Ulu|Hazal|H| Arikan|Hulya|H| Yalcin|Ebru|E| Karakaya|Jale|J|

Motivational music
Affect
Cystic fibrosis
Exercise
RPE


Maternal obesity alters brain derived neurotrophic factor (BDNF) signaling in the placenta in a sexually dimorphic manner.

Abstract:
INTRODUCTION
Obesity is a major clinical problem in obstetrics being associated with adverse pregnancy outcomes and fetal programming. Brain derived neurotrophic factor (BDNF), a validated miR-210 target, is necessary for placental development, fetal growth, glucose metabolism, and energy homeostasis. Plasma BDNF levels are reduced in obese individuals; however, placental BDNF has yet to be studied in the context of maternal obesity. In this study, we investigated the effect of maternal obesity and sexual dimorphism on placental BDNF signaling.

METHODS
BDNF signaling was measured in placentas from lean (pre-pregnancy BMI < 25) and obese (pre-pregnancy BMI>30) women at term without medical complications that delivered via cesarean section without labor. MiRNA-210, BDNF mRNA, proBDNF, and mature BDNF were measured by RT - PCR, ELISA, and Western blot. Downstream signaling via TRKB (BDNF receptor) was measured using Western blot.

RESULTS
Maternal obesity was associated with increased miRNA-210 and decreased BDNF mRNA in placentas from female fetuses, and decreased proBDNF in placentas from male fetuses. We also identified decreased mature BDNF in placentas from male fetuses when compared to female fetuses. Mir-210 expression was negatively correlated with mature BDNF protein. TRKB phosphorylated at tyrosine 817, not tyrosine 515, was increased in placentas from obese women. Maternal obesity was associated with increased phosphorylation of MAPK p38 in placentas from male fetuses, but not phosphorylation of ERK p42/44.

DISCUSSION
BDNF regulation is complex and highly regulated. Pre-pregnancy/early maternal obesity adversely affects BDNF/TRKB signaling in the placenta in a sexually dimorphic manner. These data collectively suggest that induction of placental TRKB signaling could ameliorate the placental OB phenotype, thus improving perinatal outcome.

Prince|Calais S|CS|
Maloyan|Alina|A|
Myatt|Leslie|L|

D039382:Maternal Nutritional Physiological Phenomena

Obesity
Placenta
Sexual dimorphism
Neurotrophin
microRNA


Symptoms of depression and cognitive impairment in young adults after stroke/transient ischemic attack.

Abstract: Depression and cognitive complaints are common after stroke; these issues have been studied in older populations, but not in the young. Two hundred and seventy four eligible stroke and TIA patients consented to participate and complete the Center for Epidemiologic Studies Depression Scale, and National Institute of Neurological Disorders and Stroke - Canadian Stroke Network 30-min neuropsychological battery; 57 (21%) were ≤ 50 years of age. Younger patients reported greater symptoms of depression and less executive dysfunction than older patients. This study highlights age differences in post-stroke depression symptoms and cognitive impairment, and emphasizes the need for screening across ages.

Kapoor|Arunima|A|
Scott|Courtney|C|
Lanctot|Krista L|KL|
Herrmann|Nathan|N|
Murray|Brian J|BJ|
Thorpe|Kevin E|KE|
Lien|Karen|K|
Sicard|Michelle|M|
Swartz|Richard H|RH|


Bacteremia because of Streptococcus pseudoporcinus in a Syphilis-HIV co-infected patient: A case report.

Abstract: A 43 year old male patient came to the emergency department with complaints of severe breathlessness and pedal edema with on & off fever since 15 days. The patient also gave history of sexual exposures with multiple partners. ECHO revealed moderate LV dysfunction, severe aortic regurgitation (AR), trivial mitral regurgitation (MR) with mild pulmonary edema. The patient was diagnosed as a case of severe Aortic regurgitation with atrial fibrillation. The patient was found sero-positive for HIV and Syphilis. His blood cultures obtained prior to initiation of antibiotics showed growth of small 0.5-1mm in diameter, β- hemolytic colonies on blood agar The isolate was identified to be Streptococcus pseudoporcinous by VITEK2 Compact system and was sensitive to vancomycin, linezolid, penicillin, cotrimoxazole and ciprofloxacin. Streptococcus pseudoporcinus is usually found as colonizer of female genital tract has been rarely associated with bacteremia. In the present report the patient possibly has acquired the infection from female genital tract because of his abnormal sexual behaviour. Association of Streptococcus pseudoporcinus with increased numbers of sexual partners and sexually transmitted infections suggests that further studies of this organism are warranted.

Bacteremia
streptococcus pseudoporcinus
HIV
syphilis


Screen use among young children and parental concern.

Abstract:
INTRODUCTION
An excessive technology use among young children is a cause for concern in pediatric practice.

OBJECTIVE
To assess screen use among children < 4 years old and its relation to parental concern about psychomotor development regarding motor, language, cognitive, and personal-social skills.

POPULATION AND METHODS
Survey administered to mothers and/or fathers of children aged ≥ 18 months and < 4 years seen at the outpatient office between February and May 2018. Descriptive, cross-sectional study.

RESULTS
A total of 150 surveys were completed. Combined device use in 100 %: TV, 98 %; smartphones, 80 %; tablets, 52.7 %; computers, 24 %. Average use: 2.25 h/day across all ages (standard deviation: 1.2). Use and quality: games, 60 % (non-educational, 23 %); videos, 88 % (non-educational, 20 %). Parental concern about development: 82 % had no concerns; 8.7 % was concerned about language; 9.3 %, about attention deficit; the latter two were consistent with a longer exposure time: 2.92 h/day (p = 0.0024). Parental opinion about use and effects on development: 52 %, beneficial; 12 %, no effect; 25.3 %, harmful; and 10.7 %, harmful due to excessive use; the latter two were consistent with a shorter exposure time: 1.8 h/day (p = 0.0023).

CONCLUSION
The 100 % of children use devices in combination. Parental concern about psychomotor development is expressed when exposure exceeds the current recommendations for age.

Pedrouzo|Silvina B|SB|
Peskins|Valeria|V|
Garbocci|Ana M|AM|
Sastre|Sergio G|SG|
Wasserman|Jorge|J|

parents
awareness
child
media
mobile devices


Lactic acid 5% mouth wash vs Kenalog in Orabase 0.1% for treatment and prophylaxis of recurrent aphthous ulcer.

Abstract:
BACKGROUND
The outcomes of most therapeutic modalities for recurrent aphthous ulcer (RAU) are still unsatisfactory.

AIM
To evaluate lactic acid 5% mouth wash vs Kenalog in Orabase for treatment and prophylaxis of RAU.

PATIENTS/METHODS
Forty cases with early-onset idiopathic RAU were enrolled in this study. Patients were divided into two equal groups; group A patients had used Kenalog in Orabase twice daily, and group B patients had used lactic acid 5% mouth wash 3 times daily. All patients had used the therapy for 1-2 weeks according to patients' clinical response that was evaluated according to oral clinical manifestations index (OCMI); before therapy, during course of treatments and in follow-up visits.

RESULTS
At the ends of both first and second weeks, from beginning of therapy, OCMI was reduced more in group B patients than in group A with statistically significant results. These results revealed that group B achieved more reduction in the size, pain, and healing time of RAU. During the follow-up period, group A showed 40% recurrence rate while group B showed 5% only.

CONCLUSIONS
Lactic acid 5% mouth wash is natural, safe, and effective so it is better alternative to corticosteroids for treatment and prophylaxis of RAU without any side effects.

lactic acid
Kenalog
recurrent aphthous ulcer
oral clinical manifestation index
herpetiform aphthous ulceration
vascular endothelial growth factor


Targeted doxorubicin nanotherapy strongly suppressing growth of multidrug resistant tumor in mice.

Abstract: The rational design of nanomedicine to treat multidrug resistant (MDR) tumors in vivo is described in the study. We prepared multifunctionalized Pluronic micelles that are already well-established to be responsive to low pH and redox in order to systemically deliver doxorubicin (DOX) to MDR tumors. Folic acids (FAs) were introduced on the micelle surface as tumor-targeting molecules. In vitro, the DOX-loaded micelles exerted high cytotoxicity in the DOX-resistant cells by bypassing MDR efflux. Cellular uptake studies clearly demonstrated that FA-conjugated DOX micelles (FA/DOX micelles) were efficiently internalized and accumulated in the MDR cells. In vivo studies indicated significant efficacy of FA/DOX micelles for MDR tumors in mice, and that the volume of tumors was 3 times smaller in this group than that of tumors in the free DOX group, and 8 times smaller than the tumors in the saline group. To the best of our knowledge, this methodology has been recognized to have significantly high efficacy, compared to previously reported DOX nanoparticle formulations. This superior anti-tumor efficacy of FA/DOX micelles in MDR tumor-bearing mice can be attributed to FA-targeted and -mediated endocytosis, inhibition of MDR effect, and subsequent DOX release triggered by dual stimuli (low pH and redox) inside the tumor. Given the promise of the multifunctional micelle mediated delivery on inhibition of MDR tumor growth, FA/DOX micelle platform is a much sought after goal for cancer chemotherapy, especially for cancers resistant to anticancer drugs.

Nguyen|Dai Hai|DH|
Lee|Jung Seok|JS|
Bae|Jin Woo|JW|
Choi|Jong Hoon|JH|
Lee|Yunki|Y|
Son|Joo Young|JY|
Park|Ki Dong|KD|

Doxorubicin
Pluronic micelles
Multidrug-resistant tumor
Redox-sensitive
pH-sensitive
targeted chemotherapy


Synthesis of 99mTc-labeled 2-Mercaptobenzimidazole as a novel radiotracer to diagnose tumor hypoxia.

Abstract: Discovery of 99mTc-labeled imidazole derivatives as a potential radiotracer for hypoxic tumor imaging is considered to be of great interest because of non-invasive detection capabilities. 2-Mercaptobenzimidazole (2-MBI) was successfully synthesized, characterized and radiolabeled with [99mTc (CO)3(H2O)3]+ intermediate to form 99mTc-2-MBI complex with radiochemical purity of ≥95% yield as observed by instant-thin layer chromatography (ITLC) and radio-high performance liquid chromatography (radio-HPLC). The 99mTc-2-MBI complex was observed to be stable in saline and serum with no noticeable decomposition at room temperature and 37 °C, respectively, over a time period of 24 h. Biodistribution results in Balb/c mice bearing S180 tumor show that 99mTc-2-MBI highly internalized in tumor tissue, also possess preferably high tumor/muscle and tumor/blood ratios 4.14 ± 0.77 and 3.91 ± 0.63, respectively at 24 h incubation. Scintigraphic imaging study shows 99mTc-2-MBI is visibly accumulated in hypoxic tumor tissue, suggesting it would be a promising radiotracer for early stage diagnosis of tumor hypoxia.

Rizvi|Syed Faheem Askari|SFA|
Zhang|Haixia|H|
Mehmood|Sajid|S|
Sanad|Mahmoud|M|

Radiotracer
Tumor hypoxia
Imidazole
S180 Tumor
(99m)Tc-2-MBI
Scintigraphy study


Guided Assembly of Block Copolymers in Three-Dimensional Woodpile Scaffolds.

Abstract: Three-dimensional (3D) nanofabrication using the directed self-assembly of block copolymers (BCPs) holds great promise for the nanoscale device fabrication and integration into 3D architectures over large areas with high element densities. In this work, a robust platform is developed for building 3D BCP architectures with tailored functionality using 3D micron-scale woodpile structures (WPSs), fabricated by a multiphoton polymerization technique. By completely filling the spaces of the WPSs and using the interactions of the blocks of the BCPs with the struts of the WPS, well-developed 3D nanoscopic morphologies are produced. Metal ion complexation with one block of the copolymer affords a convenient stain to highlight one of the microdomains of the copolymer for electron microscopy studies but also, with the reduction of the complexing salt to the corresponding metal, a simple strategy is shown to produce 3D constructs with nanoscopic domain resolution.

block copolymers
directed self-assembly
woodpile structures
multiphoton polymerization
laser direct writing


Management of critically ill patients with COVID-19 in ICU: statement from front-line intensive care experts in Wuhan, China.

Abstract:
BACKGROUND
The ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept all over the world, posing a great pressure on critical care resources due to large number of patients needing critical care. Statements from front-line experts in the field of intensive care are urgently needed.

METHODS
Sixteen front-line experts in China fighting against the COVID-19 epidemic in Wuhan were organized to develop an expert statement after 5 rounds of expert seminars and discussions to provide trustworthy recommendation on the management of critically ill COVID-19 patients. Each expert was assigned tasks within their field of expertise to provide draft statements and rationale. Parts of the expert statement are based on epidemiological and clinical evidence, without available scientific evidences.

RESULTS
A comprehensive document with 46 statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill COVID-19 patients. Among them, 5 recommendations were strong (Grade 1), 21 were weak (Grade 2), and 20 were experts' opinions. A strong agreement from voting participants was obtained for all recommendations.

CONCLUSION
There are still no targeted therapies for COVID-19 patients. Dynamic monitoring and supportive treatment for the restoration of tissue vascularization and organ function are particularly important.

Shang|You|Y| Pan|Chun|C| Yang|Xianghong|X| Zhong|Ming|M| Shang|Xiuling|X| Wu|Zhixiong|Z| Yu|Zhui|Z| Zhang|Wei|W| Zhong|Qiang|Q| Zheng|Xia|X| Sang|Ling|L| Jiang|Li|L| Zhang|Jiancheng|J| Xiong|Wei|W| Liu|Jiao|J| Chen|Dechang|D|


Chemical Space Charting of Different Parts of Inula nervosa Wall.: Upregulation of Expression of Nrf2 and Correlated Antioxidants Enzymes.

Abstract: The edible and medicinal part of Inula nervosa Wall. (Xiaoheiyao) is confined to its root without sufficient phytochemical and biological investigation. In this study, the secondary metabolites of root, stem, leaf, and flower of I. nervosa Wall. were visualized using Global Natural Products Social Molecular Networking (GNPS), MolNetEnhancer, XCMS(xcmsonline.scripps.edu) analysis, and `ili mapping based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) data to reveal their chemical differences. Among the 11 kinds of chemical repertoires annotated by MolNetEnhancer and 16 hits against the GNPS library, 10-isobutyryloxy-8,9-epoxythymol isobutyrate (1) was revealed as the most dominant and responsible marker between the roots and the other parts. Moreover, a battery of unique MS features as well as differential markers were discovered from different parts of the plant. The chemical differences contribute to the bioactivity differences, which presented in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH)assay and H2O2-insulted HepG2 cells and were in significant correlations with the contents of 1. real-time reverse transcription polymerase chain reaction (RT-PCR)results demonstrated that I. nervosa Wall. extracts upregulated the mRNA expression of nuclear factor E2-related factor 2(Nrf2), heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), manganese superoxide dismutase (MnSOD), and glutamate-cysteine ligase catalytic subunit (GCLC) actors involved in antioxidative response in H2O2-challenged HepG2 cells. These findings support the roots of I. nervosa Wall. as active parts of Xiaoheiyao, and also indicate the potential antioxidant activities of other parts.

Cheng|Xiang-Rong|XR|0000-0002-5553-3758 Zhao|Wei|W| Dong|Wen-le|WL| Le|Guo-Wei|GW|

D061745:Antioxidant Response Elements
D000975:Antioxidants
D001688:Biological Products
D001713:Biphenyl Compounds
D035264:Flowers
D005786:Gene Expression Regulation
D005721:Glutamate-Cysteine Ligase
D051547:Heme Oxygenase-1
D006801:Humans
D006861:Hydrogen Peroxide
D038143:Inula
D016660:NAD(P)H Dehydrogenase (Quinone)
D051267:NF-E2-Related Factor 2
D010851:Picrates
D010936:Plant Extracts
D018517:Plant Roots
D013482:Superoxide Dismutase

Nrf2
Xiaoheiyao
MolNetEnhancer
GNPS molecular networking
XCMS online


Glucocorticoid-induced CREB activation and myostatin expression in C2C12 myotubes involves phosphodiesterase-3/4 signaling.

Abstract: Muscle atrophy in metabolic conditions like chronic kidney disease (CKD) and diabetes are associated with glucocorticoid production, dysfunctional insulin/Akt/FoxO3 signaling and increased myostatin expression. We recently found that CREB, a transcription factor proposed to regulate myostatin expression, is highly phosphorylated in some wasting conditions. Based on a novel Akt-PDE3/4 signaling paradigm, we hypothesized that reduced Akt signaling contributes to CREB activation and myostatin expression. C2C12 myotubes were incubated with dexamethasone (Dex), an atrophy-inducing synthetic glucocorticoid. Akt/CREB signaling and myostatin expression were evaluated by immunoblot and qPCR analyses. Inhibitors of Akt, phosphodiesterase (PDE)-3/4, and protein kinase A (PKA) signaling were used to test our hypothesis. Incubating myotubes with Dex for 3-24 h inhibited Akt phosphorylation and enhanced CREB phosphorylation as well as myostatin mRNA and protein. Inhibition of PI3K/Akt signaling with LY294002 similarly increased CREB phosphorylation. Isobutyl-methylxanthine (IBMX, a pan PDE inhibitor), milrinone (PDE3 inhibitor) and rolipram (PDE4 inhibitor) augmented CREB phosphorylation and myostatin expression. Inhibition of protein kinase A by PKI reverted Dex- or IBMX-induced CREB phosphorylation and myostatin expression. Our study provides evidence supporting a newly identified mechanism by which a glucocorticoid-related reduction in Akt signaling contributes to myostatin expression via CREB activation.

Xie|Yang|Y|
Perry|Ben D|BD|
Espinoza|Daniel|D|
Zhang|Peng|P|
Price|S Russ|SR|

D017362:Cyclic AMP Response Element-Binding Protein

D054684:Cyclic Nucleotide Phosphodiesterases, Type 3

D054703:Cyclic Nucleotide Phosphodiesterases, Type 4

CREB
Myostatin
Glucocorticoid
Gene expression regulation
Insulin resistance
Skeletal muscle


Case Report: Induced Lactation in a Transgender Woman.

Abstract: Objective: Our report describes a case of nonpuerperal induced lactation in a transgender woman. Methods: We present the relevant clinical and laboratory findings, along with a review of the relevant literature. Results: A 30-year-old transgender woman who had been receiving feminizing hormone therapy for the past 6 years presented to our clinic with the goal of being able to breastfeed her adopted infant. After implementing a regimen of domperidone, estradiol, progesterone, and breast pumping, she was able to achieve sufficient breast milk volume to be the sole source of nourishment for her child for 6 weeks. This case illustrates that, in some circumstances, modest but functional lactation can be induced in transgender women.

induced lactation
transgender
breastfeeding
gender dysphoria


HDAC inhibitor ameliorates behavioral deficits in Mecp2308/y mouse model of Rett syndrome.

Abstract: Rett syndrome (RTT) is a rare X-linked neurodevelopmental disorder. More than 95% of classic RETT syndrome cases result from pathogenic variants in the methyl-CpG binding protein 2 (MECP2) gene. Nevertheless, it has been established that a spectrum of neuropsychiatric phenotypes is associated with MECP2 variants in both females and males. We previously reported that microtubule growth velocity and vesicle transport directionality are altered in Mecp2-deficient astrocytes from newborn Mecp2-deficient mice compared to that of their wild-type littermates suggesting deficit in microtubule dynamics. In this study, we report that administration of tubastatin A, a selective HDAC6 inhibitor, restored microtubule dynamics in Mecp2-deficient astrocytes. We furthermore report that daily doses of tubastatin A reversed early impaired exploratory behavior in male Mecp2308/y mice. These findings are a first step toward the validation of a novel treatment for RTT.

Lebrun|Nicolas|N| Delépine|Chloé|C| Selloum|Mohamed|M| Meziane|Hamid|H| Nectoux|Juliette|J| Herault|Yann|Y| Bienvenu|Thierry|T|

Rett syndrome
MeCP2
Microtubules
Astrocytes
Tubastatin A
HDAC6


Influence of Plasma Concentration of Hsa-Mir-370-3p and Cyp2d6*4 On Equilibrium Concentration of Phenazepam in Patients with Recurrent Depressive Disorder.

Abstract:
Introduction
Phenazepam is commonly administered to patients diagnosed with major depressive disorder. Some proportion of such patients do not show adequate response to treatment regimen containing phenazepam, whereas many of them experience type A adverse drug reactions. Previous studies showed that CYP2D6 IS involved in the biotransformation of phenazepam, the activity of which is highly dependent on the polymorphism of the gene encoding it. Objective. The objective of the study was to evaluate the impact of 1846G>A polymorphism of the CYP2D6 gene on the concentration/dose indicator of phenazepam, using findings on enzymatic activity of CYP2D6 (as evaluated by the 6M-THBC/pinoline ratio measurement) and on CYP2D6 expression level obtained by measuring the hsa-miR-370-3p plasma concentration levels in patients suffering from major depressive disorder.

Material and methods
The study enrolled 191 patients with recurrent depressive disorder (age -40.0 ± 16.3 years). Treatment regimen included phenazepam in an average daily dose of 6.0 ± 2.3 mg per day. Treatment efficacy was assessed using the validated psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels we performed the real-time polymerase chain reaction (PCR Real-time). The activity of CYP2D6 was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6M-THBC/pinoline). Therapeutic drug monitoring has been performed using HPLC-MS/MS.

Results
Our findings didn't reveal the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 6.0 [4.0; 8.0] and (GA) 6.0 [5.0; 7.8], p > 0.999; the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 4.0] and (GA) 3.0 [3.0; 3.0], p > 0.999. We didn't reveal a statistical significance for concentration/dose indicator of phenazepam in patients with different genotypes: (GG) 0.812 [0.558; 1.348] and (GA) 0.931 [0.630; 1.271], p = 0.645). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 22.5 [16.9; 29.8], (GA) 22.7 [15.7; 31.5], p = 0.695. At the same time, correlation analysis didn't reveal a statistically significant relationship between the phenazepam efficacy profile evaluated by changes in HAMA scale scores and the hsa-miR-370-3p plasma concentration: rs = -0.01, p = 0.866. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.07, p = 0.348. Also we did not reveal the relationship between the CYP2D6 enzymatic activity (as evaluated by 6M-THBC/pinoline ratio measurement) and the hsa-miR-370-3p plasma concentration: rs = -0.14, p = 0.056. At the same time, correlation analysis did not reveal a statistically significant relationship between the phenazepam concentration and the hsa-miR-370-3p plasma concentration: rs = -0.05, p = 0.468.

Conclusion
The effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of phenazepam was not demonstrated in a group of 191 patients with recurrent depressive disorder. At the same time, hsa-miR-370-3p does not remain a promising biomarker for assessing the level of CYP2D6 expression, because it does not correlate with encoded isoenzyme activity.

Zastrozhin|M S|MS|
Efimova|A V|AV|
Skryabin|VYu|V|
Smirnov|V V|VV|
Petukhov|A E|AE|
Pankratenko|E P|EP|
Pozdniakov|S A|SA|
Kaverina|E V|EV|
Klepikov|D A|DA|
Grishina|E A|EA|
Ryzhikova|K A|KA|
Bure|I V|IV|
Bryun|E A|EA|
Sychev|D A|DA|

CYP2D6
phenazepam
biotransformation
alcohol use disorder
depressive spectrum disorders
personalized medicine
pharmacogenetics


Early brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study.

Abstract:
BACKGROUND
Traumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not.

DESIGN
Multicentre prospective cohort study starting in 2018. Imaging data are acquired around day 14 post-injury, detection of seizure events occurred early (within 1 week) and late (up to 90 days post-TBI).

RESULTS
From a sample of 96 patients surviving moderate-to-severe TBI, we performed shape analysis of local volume deficits in subcortical areas (analysable sample: 57 patients; 35 no seizure, 14 early, 8 late) and cortical ribbon thinning (analysable sample: 46 patients; 29 no seizure, 10 early, 7 late). Right hippocampal volume deficit and inferior temporal cortex thinning demonstrated a significant effect across groups. Additionally, the degree of left frontal and temporal pole thinning, and clinical score at the time of the MRI, could differentiate patients experiencing early seizures from patients not experiencing them with 89% accuracy.

CONCLUSIONS AND RELEVANCE
Although this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.

Lutkenhoff|Evan S|ES|
Shrestha|Vikesh|V|
Ruiz Tejeda|Jesus|J|
Real|Courtney|C|
McArthur|David L|DL|
Duncan|Dominique|D|
La Rocca|Marianna|M|
Garner|Rachael|R|
Toga|Arthur W|AW|
Vespa|Paul M|PM|
Monti|Martin M|MM|0000-0001-5511-3780
|||


Prazosin for Trauma Nightmares and Sleep Disturbances in Combat Veterans with Post-Traumatic Stress Disorder.

Abstract:
BACKGROUND
Prazosin is significantly effective to reduce sleep disturbance and trauma nightmare in patients with post-traumatic stress disorder (PTSD); however, results of different studies were evaluated.

OBJECTIVES
The current randomized clinical trial aimed to assess the effects of prazosin on sleep parameters and nightmares among veterans with chronic PTSD.

MATERIALS AND METHODS
Thirty-two veterans with chronic war-induced PTSD and distressing nightmares were randomized into prazosin and placebo groups for eight weeks. The main symptoms were qualified using the recurrent distressing dreams item of the clinician administered PTSD scale (CAPS) and the daytime symptom severity was measured by PTSD checklist (PCL) and the objective sleep quality assessment by actigraphy.

RESULTS
Compared with placebo, prazosin had no significant effects on reduction of daytime symptoms (P = 0.69) and frequency and intensity of trauma-related nightmares. Also, there were no significant differences between pre- and post-treatment actigraphy measurements (P > 0.05).

CONCLUSIONS
The study findings showed that prazosin had no significant effect on reduction of PTSD symptoms as well as nightmares among veterans with chronic PTSD. Further clinical trials are needed to define the effect of prazosin on sleep physiology and whether such effects regarding the therapeutic response.

Khazaie|Habibolah|H|
Nasouri|Marzie|M|
Ghadami|Mohammad Rasoul|MR|

Prazosin
Nightmare
Sleep Disturbance
Post-Traumatic Stress Disorder


Diversification of Fungal Chitinases and Their Functional Differentiation in Histoplasma capsulatum.

Abstract: Chitinases enzymatically hydrolyze chitin, a highly abundant and utilized polymer of N-acetyl-glucosamine. Fungi are a rich source of chitinases; however, the phylogenetic and functional diversity of fungal chitinases are not well understood. We surveyed fungal chitinases from 373 publicly available genomes, characterized domain architecture, and conducted phylogenetic analyses of the glycoside hydrolase (GH18) domain. This large-scale analysis does not support the previous division of fungal chitinases into three major clades (A, B, C) as chitinases previously assigned to the "C" clade are not resolved as distinct from the "A" clade. Fungal chitinase diversity was partly shaped by horizontal gene transfer, and at least one clade of bacterial origin occurs among chitinases previously assigned to the "B" clade. Furthermore, chitin-binding domains (including the LysM domain) do not define specific clades, but instead are found more broadly across clades of chitinases. To gain insight into biological function diversity, we characterized all eight chitinases (Cts) from the thermally dimorphic fungus, Histoplasma capsulatum: six A clade, one B clade, and one formerly classified C clade chitinases. Expression analyses showed variable induction of chitinase genes in the presence of chitin but preferential expression of CTS3 in the mycelial stage. Activity assays demonstrated that Cts1 (B-I), Cts2 (A-V), Cts3 (A-V), Cts4 (A-V) have endochitinase activities with varying degrees of chitobiosidase function. Cts6 (C-I) has activity consistent with N-acetyl-glucosaminidase exochitinase function and Cts8 (A-II) has chitobiase activity. These results suggest chitinase activity is variable even within subclades and that predictions of functionality require more sophisticated models.

Goughenour|Kristie D|KD|
Whalin|Janice|J|
Slot|Jason C|JC|
Rappleye|Chad A|CA|

D002688:Chitinases
D019143:Evolution, Molecular
D005656:Fungal Proteins
D016681:Genome, Fungal
D006658:Histoplasma
D000072417:Protein Domains


Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma.

Abstract: Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18-25 year old controls and 50-80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.

Kohli|Manish|M|0000-0002-9735-6614 Tan|Winston|W| Vire|Bérengère|B| Liaud|Pierre|P| Blairvacq|Mélina|M| Berthier|Frederic|F| Rouison|Daniel|D| Garnier|George|G| Payen|Léa|L| Cousin|Thierry|T| Joubert|Dominique|D| Prieur|Alexandre|A|

hPG80
circulating progastrin
IMDC
blood-based prognostic biomarker
metastatic renal cell carcinoma (mRCC)


Population segmentation of type 2 diabetes mellitus patients and its clinical applications - a scoping review.

Abstract:
BACKGROUND
Population segmentation permits the division of a heterogeneous population into relatively homogenous subgroups. This scoping review aims to summarize the clinical applications of data driven and expert driven population segmentation among Type 2 diabetes mellitus (T2DM) patients.

METHODS
The literature search was conducted in Medline®, Embase®, Scopus® and PsycInfo®. Articles which utilized expert-based or data-driven population segmentation methodologies for evaluation of outcomes among T2DM patients were included. Population segmentation variables were grouped into five domains (socio-demographic, diabetes related, non-diabetes medical related, psychiatric / psychological and health system related variables). A framework for PopulAtion Segmentation Study design for T2DM patients (PASS-T2DM) was proposed.

RESULTS
Of 155,124 articles screened, 148 articles were included. Expert driven population segmentation approach was most commonly used, of which judgemental splitting was the main strategy employed (n = 111, 75.0%). Cluster based analyses (n = 37, 25.0%) was the main data driven population segmentation strategies utilized. Socio-demographic (n = 66, 44.6%), diabetes related (n = 54, 36.5%) and non-diabetes medical related (n = 18, 12.2%) were the most used domains. Specifically, patients' race, age, Hba1c related parameters and depression / anxiety related variables were most frequently used. Health grouping/profiling (n = 71, 48%), assessment of diabetes related complications (n = 57, 38.5%) and non-diabetes metabolic derangements (n = 42, 28.4%) were the most frequent population segmentation objectives of the studies.

CONCLUSIONS
Population segmentation has a wide range of clinical applications for evaluating clinical outcomes among T2DM patients. More studies are required to identify the optimal set of population segmentation framework for T2DM patients.

Population segmentation
Scoping review
Cluster analysis
Data analysis
Diabetes mellitus, type 2
Latent class analysis
Outcome assessment, health care
Patient outcome assessment


Renal histopathology in critically ill patients with Septic Acute Kidney Injury(S-AKI).

Abstract:
PURPOSE
To describe the kidney histopathology of patients with S-AKI and correlate the histological findings with AKI severity, presence of septic shock, and the degree of multiple organic dysfunction (MOD) using the SOFA score.

MATERIALS AND METHODS
This was a prospective, observational, and analytical study of a cohort of critically ill patients with S-AKI who died from sepsis at the "Hospital Español" intensive care unit (ICU). Kidney necropsies were performed within 2 h after death.

RESULTS
We considered twenty (20) patients, with all of them exhibiting S-AKI stage 3 at the same time. In renal histopathology analysis, nonspecific tubulointerstitial (TI) lesions were found in almost all patients (95%). The more frequently found nonspecific TI lesions involved leukocyte infiltration (85%). Necrotic TI lesions were found in 6 patients (30%), and necrotic tubular cell casts were the most frequent lesions (50% of patients). It was not possible to demonstrate an association between the presence of necrotic TI lesions and factors such as the APACHE II score, the global SOFA score, ICU stays, AKI length and renal replacement therapy (RRT).

CONCLUSIONS
The main histopathological findings in kidney necropsies in patients with S-AKI KDIGO 3, showed nonspecific TI lesions, and TI necrosis was only observed in 30% of the cases; therefore, S-AKI cannot be considered to be synonymous with acute tubular necrosis (ATN).

Tenzi|Jordán|J| Hurtado|Javier|J| Nin|Nicolás|N| Rodriguez|Fernando|F| Molina|Claudia|C| Aunchayna|Maria|M|

Renal histopathology
Septic acute kidney injury


Soil humic-like organic compounds in prescribed fire emissions using nuclear magnetic resonance spectroscopy.

Abstract: Here we present the chemical characterization of the water-soluble organic carbon fraction of atmospheric aerosol collected during a prescribed fire burn in relation to soil organic matter and biomass combustion. Using nuclear magnetic resonance spectroscopy, we observed that humic-like substances in fire emissions have been associated with soil organic matter rather than biomass. Using a chemical mass balance model, we estimated that soil organic matter may contribute up to 41% of organic hydrogen and up to 27% of water-soluble organic carbon in fire emissions. Dust particles, when mixed with fresh combustion emissions, substantially enhances the atmospheric oxidative capacity, particle formation and microphysical properties of clouds influencing the climatic responses of atmospheric aeroso. Owing to the large emissions of combustion aerosol during fires, the release of dust particles from soil surfaces that are subjected to intense heating and shear stress has, so far, been lacking.

Chalbot|M-C|MC|
Nikolich|G|G|
Etyemezian|V|V|
Dubois|D W|DW|
King|J|J|
Shafer|D|D|
Gamboa da Costa|G|G|
Hinton|J F|JF|
Kavouras|I G|IG|

Nuclear magnetic resonance
Organic carbon
Aerosol
Biomass burning
Mineral dust
Wildfires


The impact of insecticide-treated cloth targets on the survival of Stegomyia polynesiensis (= Aedes polynesiensis) under laboratory and semi-field conditions in French Polynesia.

Abstract: The impact of deltamethrin-impregnated cloth targets on Stegomyia polynesiensis (= Aedes polynesiensis) (Marks) (Diptera: Culicidae) was assessed under laboratory and semi-field settings in French Polynesia. Stegomyia polynesiensis females were released into small laboratory cages and large field cages containing either a deltamethrin-treated or an untreated navy blue cloth, and mosquito knock-down and mortality were assessed. The 24-h mortality rate in mosquitoes exposed to the insecticide-treated target in small cages was 98.0%. These mosquitoes also demonstrated significantly higher levels of knock-down than those exposed to the untreated target. Mortality in field cages was assessed at 24 and 48 h. The 24-h mortality rate in mosquitoes exposed to the control target was 31.2%, whereas that in those exposed to the deltamethrin-treated target was 54.3%. The 48-h mortality rate was also elevated in mosquitoes exposed to the deltamethrin-treated target, but this result did not differ significantly from that observed in mosquitoes exposed to the control target. The significant suppression of female S. polynesiensis by deltamethrin-treated resting targets in this study indicates that these targets could play a role in the control of an important disease vector in the South Pacific region.

Chambers|E W|EW|
Bossin|H C|HC|
Ritchie|S A|SA|
Russell|R C|RC|
Dobson|S L|SL|


Nucleotide polymorphism and copy number variant detection using exome capture and next-generation sequencing in the polyploid grass Panicum virgatum.

Abstract: Switchgrass (Panicum virgatum) is a polyploid, outcrossing grass species native to North America and has recently been recognized as a potential biofuel feedstock crop. Significant phenotypic variation including ploidy is present across the two primary ecotypes of switchgrass, referred to as upland and lowland switchgrass. The tetraploid switchgrass genome is approximately 1400 Mbp, split between two subgenomes, with significant repetitive sequence content limiting the efficiency of re-sequencing approaches for determining genome diversity. To characterize genetic diversity in upland and lowland switchgrass as a first step in linking genotype to phenotype, we designed an exome capture probe set based on transcript assemblies that represent approximately 50 Mb of annotated switchgrass exome sequences. We then evaluated and optimized the probe set using solid phase comparative genome hybridization and liquid phase exome capture followed by next-generation sequencing. Using the optimized probe set, we assessed variation in the exomes of eight switchgrass genotypes representing tetraploid lowland and octoploid upland cultivars to benchmark our exome capture probe set design. We identified ample variation in the switchgrass genome including 1,395,501 single nucleotide polymorphisms (SNPs), 8173 putative copy number variants and 3336 presence/absence variants. While the majority of the SNPs (84%) detected was bi-allelic, a substantial number was tri-allelic with limited occurrence of tetra-allelic polymorphisms consistent with the heterozygous and polyploid nature of the switchgrass genome. Collectively, these data demonstrate the efficacy of exome capture for discovery of genome variation in a polyploid species with a large, repetitive and heterozygous genome.

Evans|Joseph|J|
Kim|Jeongwoon|J|
Childs|Kevin L|KL|
Vaillancourt|Brieanne|B|
Crisovan|Emily|E|
Nandety|Aruna|A|
Gerhardt|Daniel J|DJ|
Richmond|Todd A|TA|
Jeddeloh|Jeffrey A|JA|
Kaeppler|Shawn M|SM|
Casler|Michael D|MD|
Buell|C Robin|CR|

copy number variant
exome
Panicum virgatum
switchgrass
presence/absence variant
polyploidy


Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure.

Abstract:
WHAT IS KNOWN AND OBJECTIVE
Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist.

METHODS
A literature review was conducted using MEDLINE, Ovid, Science Direct, Web of Science and Cochrane Database of Systematic Reviews databases with keywords:hypertension, hypotension, renin-angiotensin-aldosterone system, dopaminergic receptors, blood pressure, antipsychotics. Inclusion criteria were human or animal studies, systematic reviews, meta-analyses, randomized controlled trials, case report/series, published in selected for inclusion.

RESULTS AND DISCUSSION
All 5 dopamine receptor subtypes (ie D1, D2, D3, D4 and D5) regulate sodium excretion and BP. The D1, D3 and D4 receptors interact directly with the renin-angiotensin-aldosterone system, whereas D2 and D5 receptors directly interact with the sympathetic nervous system to regulate BP. Use of dopaminergic agonists or antagonists could therefore disturb the regulation of BP by dopamine receptors.

WHAT IS NEW AND CONCLUSION
Based upon this review, individuals on antipsychotic agents, particularly clozapine, should be routinely monitored for hypertension, and addition of antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is indicated if hypertension occurs.

D000818:Animals
D000959:Antihypertensive Agents
D014150:Antipsychotic Agents
D001794:Blood Pressure
D018492:Dopamine Antagonists
D006801:Humans
D011954:Receptors, Dopamine

antipsychotics
blood pressure
hypertension
anti-hypertensives
cardiology
neuropharmacology


Small peptides hydrolysis in dry-cured meats.

Abstract: Large amounts of different peptides are naturally generated in dry-cured meats as a consequence of the intense proteolysis mechanisms which take place during their processing. In fact, meat proteins are extensively hydrolysed by muscle endo-peptidases (mainly calpains and cathepsins) followed by exo-peptidases (mainly, tri- and di-peptidyl peptidases, dipeptidases, aminopeptidases and carboxypeptidases). The result is a large amount of released free amino acids and a pool of numerous peptides with different sequences and lengths, some of them with interesting sequences for bioactivity. This manuscript is presenting the proteomic identification of small peptides resulting from the hydrolysis of four target proteins (glyceraldehyde-3-phosphate dehydrogenase, beta-enolase, myozenin-1 and troponin T) and discusses the enzymatic routes for their generation during the dry-curing process. The results indicate that the hydrolysis of peptides follows similar exo-peptidase mechanisms. In the case of dry-fermented sausages, most of the observed hydrolysis is the result of the combined action of muscle and microbial exo-peptidases except for the hydrolysis of di- and tri-peptides, mostly due to microbial di- and tri-peptidases, and the release of amino acids at the C-terminal that appears to be mostly due to muscle carboxypeptidases.

Mora|Leticia|L| Gallego|Marta|M| Escudero|Elizabeth|E| Reig|Milagro|M| Aristoy|M-Concepción|MC| Toldrá|Fidel|F|

Peptides Proteolysis Peptidases Proteomics Enzymes


The Lytic Siphophage vB_StyS-LmqsSP1 Reduces the Number of Salmonella enterica Serovar Typhimurium Isolates on Chicken Skin.

Abstract: Phage-based biocontrol of bacteria is considered a natural approach to combat foodborne pathogens. Salmonella spp. are notifiable and highly prevalent pathogens that cause foodborne diseases worldwide. In this study, six bacteriophages were isolated and further characterized that infect food-derived Salmonella isolates from different meat sources. The siphovirus VB_StyS-LmqsSP1, which was isolated from a cow's nasal swab, was further subjected to in-depth characterization. Phage-host interaction investigations in liquid medium showed that vB_StyS-LmqsSP1 can suppress the growth of Salmonella species isolates at 37°C for 10 h and significantly reduce the bacterial titer at 4°C. A reduction of 1.4 to 3 log units was observed in investigations with two food-derived Salmonella isolates and one reference strain under cooling conditions using multiplicities of infection (MOIs) of 104 and 105. Phage application on chicken skin resulted in a reduction of about 2 log units in the tested Salmonella isolates from the first 3 h throughout a 1-week experiment at cooling temperature and with an MOI of 105. The one-step growth curve analysis using vB_StyS-LmqsSP1 demonstrated a 60-min latent period and a burst size of 50 to 61 PFU/infected cell for all tested hosts. Furthermore, the genome of the phage was determined to be free from genes causing undesired effects. Based on the phenotypic and genotypic properties, LmqsSP1 was assigned as a promising candidate for biocontrol of Salmonella enterica serovar Typhimurium in food. IMPORTANCE Salmonella enterica is one of the major global causes of foodborne enteritis in humans. The use of chemical sanitizers for reducing bacterial pathogens in the food chain can result in the spread of bacterial resistance. Targeted and clean-label intervention strategies can reduce Salmonella contamination in food. The significance of our research demonstrates the suitability of a bacteriophage (vB_StyS-LmqsSP1) for biocontrol of Salmonella enterica serovar Typhimurium on poultry due to its lytic efficacy under conditions prevalent in food production environments.

Shakeri|Golshan|G|0000-0001-7709-7611
Hammerl|Jens A|JA|0000-0002-6930-4358
Jamshidi|Abdollah|A|
Ghazvini|Kiarash|K|
Rohde|Manfred|M|
Szabo|Istvan|I|
Kehrenberg|Corinna|C|
Plötz|Madeleine|M|
Kittler|Sophie|S|0000-0001-6295-5935

chicken
biocontrol
phage
Salmonella Typhimurium
foodborne zoonoses
phage biocontrol
phage therapy


Testing for Hepatitis C in Pregnancy: the Time has Come for Routine Rather than Risk-based.

Abstract:
Purpose of review
The purpose of this review is to discuss the reasons for HCV testing during pregnancy and to review what is known about antiviral treatment during pregnancy.

Recent findings
Hepatitis C virus affects over 3 million persons in the United States and is one of the leading infectious causes of death. While HCV is most commonly transmitted via parenteral exposures, thus affecting people who inject drugs, it is also transmitted from mother-to-child. Due to an expanding opioid crisis, an increasing number of women of childbearing age are now infected, resulting in transmission to infants. Risk-based screening has never been proven effective and thus universal screening of pregnant women for HCV infection has been recommended.

Summary
Obstetricians may play a key role in the U.S. by implementing universal testing for HCV in pregnant women, thereby enhancing the health of mothers and identifying children at risk.

Kushner|Tatyana|T|
Chappell|Catherine A|CA|
Kim|Arthur Y|AY|

testing
pregnancy
antiviral treatment
hepatitis C virus
perinatal transmission


Hydroxyl radical-based and sulfate radical-based photocatalytic advanced oxidation processes for treatment of refractory organic matter in semi-aerobic aged refuse biofilter effluent arising from treating landfill leachate.

Abstract: In this study, three photolytic advanced oxidation processes (AOPs) were applied to the treatment of refractory organic matter in semi-aerobic aged refuse biofilter (SAARB) effluent, and the treatment efficiencies of the three AOPs were systematically compared. The AOPs combined ultraviolet (UV) radiation with either hydrogen peroxide (UV-H2O2), peroxymonosulfate (UV-PMS) or both oxidants (UV-PMS/H2O2). The effects of key parameters on degradation characteristics of refractory organics, and the contribution of reactive oxygen species were systematically studied. Results indicated that UV radiation can greatly enhance treatment efficiencies of both PMS and H2O2. Furthermore, decreasing n(H2O2)/n(PMS) ratio and decreasing the reaction pH can increase treatment efficiency for refractory organics. Compared on the basis of chemical oxygen demand (COD), treatment efficiency followed the order UV-PMS (COD removal 37.39%) > UV-PMS/H2O2 (30.51%) > UV-H2O2 (28.59%) which is consistent with results from ultraviolet-visible spectra analysis. HO• and SO4•- were both identified in the UV-PMS/H2O2 and UV-PMS processes. In the UV-PMS process, SO4•- was the dominant ROS, which suggested that SO4•--based AOPs are better than HO•-based AOPs for degrading refractory organics contained in SAARB effluent. Parallel factor (PARAFAC) analysis indicated that UV-based AOPs were effective in degrading humic- and fulvic-like substances in the SAARB leachate, and the UV-PMS process achieved a much better degradation efficiency of refractory organics in the leachate than did the UV-PMS/H2O2 and the UV-H2O2 processes. Furthermore, the best treatment efficiency was achieved by the UV-PMS process and this process also consumed the least electrical energy. This study provides a theoretical reference for refractory organics degradation in SAARB effluent by UV-catalyzed AOPs.

Guo|Shengpeng|S| Wang|Qing|Q| Luo|Chengjie|C| Yao|Jiangang|J| Qiu|Zhongping|Z| Li|Qibin|Q|

Refractory organic matter
Semi-aerobic aged refuse biofilter
AOPs
UV
PMS
H(2)O(2)


Chiral Recognition of Carboxylate Anions by (R)-BINOL-Based Macrocyclic Receptors.

Abstract: Three (R)-BINOL-based macrocyclic receptors obtained via double-amidation reaction were used for chiral recognition of four anions derived from α-hydroxy and α-amino acids. The structural factors of hosts and guests that affect chiral recognition processes were also investigated, indicating that the proper geometry of both receptor and guest molecules plays a crucial role in effective enantio-discrimination.

chiral recognition
macrocyclic receptors
BINOL
chiral anions
coalescence


Transcriptomic responses in rainbow trout gills upon infection with viral hemorrhagic septicemia virus (VHSV).

Abstract: It has been previously demonstrated that even though the fin bases constitute the main portal of entry of viral hemorrhagic septicemia virus (VHSV) in rainbow trout (Oncorhynchus mykiss), an important number of chemokine genes are up-regulated in the gills upon bath exposure to the virus. Because chemokines mediate the recruitment of leukocytes through the action of specific chemokine receptors, in the current study, we have studied the transcription of several immune genes in response to a VHSV bath infection in the gills, focusing both on chemokine receptor genes and on genes characteristic of distinct leukocyte populations such as IgM, IgD, IgT, CD4, CD8, perforin and MHC-II. We have studied the response to the virus in naïve fish as well as in fish that had been previously intramuscularly (i.m.) injected with a VHSV DNA vaccine. Additionally, we have sorted both IgM(+) and CD8(+) cells from the gills of naïve and infected animals to study some of these up-regulated genes in specific leukocyte populations. Our results indicate that despite the low replication level, VHSV provokes an up-regulation of IgM, IgT, CD3 and perforin transcription together with the up-regulation of CCR7, CCR9, CXCR3B and CXCR4 mRNA levels. Interestingly, MHC-II mRNA was up-regulated and CCR7 was down-modulated in IgM(+) cells from infected gills, whereas perforin, CCR7 and CXCR4 mRNA levels were higher in sorted CD8(+) cells from infected animals. Surprisingly, when fish had been previously injected with either the empty plasmid or the VHSV DNA vaccine, these up-regulations in immune gene transcription were no longer observed. Our results point to the gills as an important site for innate and acquired viral defense.

Aquilino|Carolina|C| Castro|Rosario|R| Fischer|Uwe|U| Tafalla|Carolina|C|

Viral hemorrhagic septicemia virus (VHSV)


Primary Cilia as Signaling Hubs in Health and Disease.

Abstract: Primary cilia detect extracellular cues and transduce these signals into cells to regulate proliferation, migration, and differentiation. Here, the function of primary cilia as signaling hubs of growth factors and morphogens is in focus. First, the molecular mechanisms regulating the assembly and disassembly of primary cilia are described. Then, the role of primary cilia in mediating growth factor and morphogen signaling to maintain human health and the potential mechanisms by which defects in these pathways contribute to human diseases, such as ciliopathy, obesity, and cancer are described. Furthermore, a novel signaling pathway by which certain growth factors stimulate cell proliferation through suppression of ciliogenesis is also described, suggesting novel therapeutic targets in cancer.

ciliopathy
obesity
cancer
receptor tyrosine kinases
ubiquitin‐mediated protein degradation


Functional Morphology of Thecal Glands in the Ovary of Japanese Quails (Coturnix japonica).

Abstract: The role of thecal glands in the ovary of birds remains controversial. Using transmission electron microscopy and immunohistochemistry, immunohistochemical localisation of cyclooxygenase I and II (COX-1 and COX-2), oestrogen receptor α and β (ER-α and ER-β), androgen receptor (AR) and progesterone receptor (PR), a detailed analysis of the thecal glands was performed. Our ultrastructural studies revealed that the thecal glands of the quail ovary consist of 2 cell types, steroid-producing cells (SPCs) and enclosing cells (ENCs). The SPCs are large, light cells containing a varying number of lipid droplets. Their cytoplasm is characterised by a large amount of smooth endoplasmic reticulum. The ENCs are always located at the periphery of the gland. Some ENCs contain an abundant number of microfilaments, but lipid droplets and dense bodies were rare. Within 1 gland, SPCs with distinct COX-2 immunostaining were interspersed between usually larger numbers of moderately COX-2-positive cells. A completely different staining pattern was observed for COX-1, where the cytoplasm of the ENCs was distinctly immunopositive. The SPCs stained only weakly with antibodies to COX-1. The thecal glands showed distinct reactions for ER-β but only a weak to negative one for ER-α, PR, and AR. Our immunohistochemical and ultrastructural data support our hypothesis that the thecal glands of the quail are involved in steroid hormone and prostaglandin synthesis. The prostaglandins secreted by the thecal glands probably contribute to the ovulation of the follicle first in the hierarchy.

Thecal glands
Ovary
Quail
Immunohistochemistry
Ultrastructure


De novo screening of disease-resistant genes from the chromosome-level genome of rare minnow using CRISPR-cas9 random mutation.

Abstract:
BACKGROUND
Mutants are important for the discovery of functional genes and creation of germplasm resources. Mutant acquisition depends on the efficiency of mutation technology and screening methods. CRISPR-Cas9 technology is an efficient gene editing technology mainly used for editing a few genes or target sites, which has not been applied for the construction of random mutant libraries and for the de novo discovery of functional genes.

RESULTS
In this study, we first sequenced and assembled the chromosome-level genome of wild-type rare minnow (Gobiocypris rarus) as a susceptible model of hemorrhagic disease, obtained a 956.05 Mb genome sequence, assembled the sequence into 25 chromosomes, and annotated 26,861 protein-coding genes. Thereafter, CRISPR-Cas9 technology was applied to randomly mutate the whole genome of rare minnow with the conserved bases (TATAWAW and ATG) of the promoter and coding regions as the target sites. The survival rate of hemorrhagic disease in the rare minnow gradually increased from 0% (the entire wild-type population died after infection) to 38.24% (F3 generation). Finally, 7 susceptible genes were identified via genome comparative analysis and cell-level verification based on the rare minnow genome.

CONCLUSIONS
The results provided the genomic resources for wild-type rare minnow, and confirmed that the random mutation system designed using CRISPR-Cas9 technology in this study is simple and efficient and is suitable for the de novo discovery of functional genes and creation of a germplasm resource related to qualitative traits.

genome
rare minnow
CRISPR-Cas9
mutant
germplasm resource


Establishing versus preserving impressions: Predicting success in the multiple audience problem.

Abstract: People sometimes seek to convey discrepant impressions of themselves to different audiences simultaneously. Research suggests people are generally successful in this "multiple audience problem." Adding to previous research, the current research sought to examine factors that may limit this success by measuring social anxiety and placing participants into situations requiring them to either establish or preserve multiple impressions simultaneously. In general, participants were more successful when preserving previously conveyed impressions than when establishing impressions for the first time. In contrast, social anxiety did not affect multiple audience success. In all, this research offers valuable insight into potential challenges that people face in many social situations.

Nichols|Austin Lee|AL|
Cottrell|Catherine A|CA|

Multiple audience problem
Social anxiety
Audience familiarity
Impression management
Self-presentation


[Retracted] Upregulation of microRNA‑27b contributes to the migration and invasion of gastric cancer cells via the inhibition of sprouty2‑mediated ERK signaling.

Abstract: Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the Transwell cell migration assay data shown in Fig. 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 13: 2267‑2272, 2016; DOI: 10.3892/mmr.2016.4779].

Jiang|Juan|J| Yi|Bo|B| Qin|Chunxiang|C| Ding|Siqing|S| Cao|Wei|W|


Screen-Printed Electrode-Based Sensors for Food Spoilage Control: Bacteria and Biogenic Amines Detection.

Abstract: Food spoilage is caused by the development of microorganisms, biogenic amines, and other harmful substances, which, when consumed, can lead to different health problems. Foodborne diseases can be avoided by assessing the safety and freshness of food along the production and supply chains. The routine methods for food analysis usually involve long analysis times and complex instrumentation and are performed in centralized laboratories. In this context, sensors based on screen-printed electrodes (SPEs) have gained increasing importance because of their advantageous characteristics, such as ease of use and portability, which allow fast analysis in point-of-need scenarios. This review provides a comprehensive overview of SPE-based sensors for the evaluation of food safety and freshness, focusing on the determination of bacteria and biogenic amines. After discussing the characteristics of SPEs as transducers, the main bacteria, and biogenic amines responsible for important and common foodborne diseases are described. Then, SPE-based sensors for the analysis of these bacteria and biogenic amines in food samples are discussed, comparing several parameters, such as limit of detection, analysis time, and sample type.

bacteria
biogenic amines
food analysis
screen-printed electrode
biosensor
electroanalysis
electrochemical sensor
histamine
immunosensor


Can teaching hospitals use serial formative OSCEs to improve student performance?

Abstract:
BACKGROUND
We report on interns' clinical competence and experiences of an objective structured clinical examination (OSCE) training program over 3 years. We aimed to determine whether repeated formative OSCEs allow teaching hospitals to improve the effectiveness of clinical training and help interns to achieve high scores in the national summative OSCE.

METHODS
This study included 207 participants, among whom 82 were interns who had completed four mock OSCEs and a national OSCE at the clinical center of Cathay General Hospital (CGH). The other 125 participants were final-year medical students from Fu-Jen University who had completed the national OSCE between 2013 and 2015 at one of four teaching hospitals (including CGH). CGH interns were categorized into three groups according to the medical school attended and Fu-Jen University students were grouped according to their training hospitals. CGH held four mock OSCEs (30 stations), whereas each of the four training hospitals for Fu-Jen students each held one or two OSCEs (6-12 stations) annually. Differences in the mean OSCE scores among groups were analyzed. The medical school attended, pre-internship OSCE experience and the frequency of mock OSCEs held by training hospitals were independent factors in this study.

RESULTS
The cumulative mean scores for five OSCEs among three groups of students trained at CGH tended to increase from the first OSCE (OSCE1) to the fifth (OSCE5). The mean score of the students who attended Fu-Jen Medical School was higher than that of students who graduated from foreign medical schools in all five OSCEs; however, the differences were significant only for OSCE2 (P = 0.022) and OSCE3 (P = 0.027). The mean national OSCE scores of FJU students showed no statistically significant differences among the four training hospitals for 2013; however, students training at CGH had significantly higher mean scores in the 2014 (P = 0.001) and 2015 (P = 0.005) OSCEs compared with students training at the other three hospitals.

CONCLUSIONS
Serial administration of formative OSCEs by teaching hospitals enhances the performance of students on the sequential summative OSCE. Such programs provide multiple opportunities for students to practice their clinical skills, and for faculty to develop their teaching, assessment and consensus building skills.

D006784:Hospitals, Teaching
D006801:Humans
D007396:Internship and Residency
D010808:Physical Examination


Gauging megadiversity with optimized and standardized sampling protocols: A case for tropical forest spiders.

Abstract: Characterizing and monitoring biodiversity and assessing its drivers require accurate and comparable data on species assemblages, which, in turn, should rely on efficient and standardized field collection. Unfortunately, protocols that follow such criteria remain scarce and it is unclear whether they can be applied to megadiverse communities, whose study can be particularly challenging. Here, we develop and evaluate the first optimized and standardized sampling protocol for megadiverse communities, using tropical forest spiders as a model taxon. We designed the protocol COBRA-TF (Conservation Oriented Biodiversity Rapid Assessment for Tropical Forests) using a large dataset of semiquantitative field data from different continents. This protocol combines samples of different collecting methods to obtain as many species as possible with minimum effort (optimized) and widest applicability and comparability (standardized). We ran sampling simulations to assess the efficiency of COBRA-TF (optimized, non-site-specific) and its reliability for estimating taxonomic, phylogenetic, and functional diversity, and community structure by comparing it with (1) commonly used expert-based ad hoc protocols (nonoptimized, site-specific) and (2) optimal protocols (optimized, site-specific). We then tested the performance and feasibility of COBRA-TF in the field. COBRA-TF yielded similar results as ad hoc protocols for species (observed and estimated) and family richness, phylogenetic and functional diversity, and species abundance distribution. Optimal protocols detected more species than COBRA-TF. Data from the field test showed high sampling completeness and yielded low numbers of singletons and doubletons. Optimized and standardized protocols can be as effective in sampling and studying megadiverse communities as traditional sampling, while allowing data comparison. Although our target taxa are spiders, COBRA-TF can be modified to apply to any highly diverse taxon and habitat as long as multiple collecting techniques exist and the unit effort per sample is comparable. Protocols such as COBRA-TF facilitate studying megadiverse communities and therefore may become essential tools for monitoring community changes in space and time, assessing the effects of disturbances and selecting conservation areas.

Malumbres-Olarte|Jagoba|J|
Scharff|Nikolaj|N|
Pape|Thomas|T|
Coddington|Jonathan A|JA|
Cardoso|Pedro|P|

Araneae
Arthropoda
Udzungwa Mountains
optimization algorithm
rapid biodiversity assessment
sampling methodology
species richness


Effects of Losartan vs. Enalapril on the Markers of Metabolic Syndrome.

Abstract:
OBJECTIVE
To compare the effects of losartan and enalapril on the markers of metabolic syndrome.

METHODS
One hundred and twenty six newly diagnosed hypertensive patients having other markers of metabolic syndrome participated in this study. The study was performed in the department of pharmacology, college of medicine at Ibn-Sina Teaching Hospital in Mosul city, Iraq, during the period between December 2007 and June 2009. The patients were divided into 2 main groups: 1) Losartan group: consisted of 60 patients, and 2) enalapril group: Consisted of 66 patients. Waist circumference, weight, Body mass index, blood pressure, serum glucose concentration, triglyceride and HDL-cholestrol were measured before and after administration of therapy. The effects of therapy were assessed by statistically comparing the results before and after the drug administration.

RESULTS
Comparison of waist circumference, blood pressure, FSG, triglycerides of the patients before drug administration (baseline data), with those of the controls showed a significant elevation, while HDL-cholesterol showed a significant reduction. A significant reduction of waist circumference, BP, FSG and a significant elevation of HDL-cholesterol were also noted after therapy with both losartan and enalapril.

CONCLUSION
Both losartan and enalapril produced a significant reduction of markers of metabolic syndrome and may be regarded as effective drugs for treatment of hypertension in patients with markers of metabolic syndrome.

Al-Thanoon|Zeina A|ZA|
Mahmood|Isam H|IH|

Losartan
Enalapril
Metabolic syndrome
Hypertension


LGR5 overexpression confers poor relapse-free survival in breast cancer patients.

Abstract:
BACKGROUND
Cancer stem cells (CSCs) are believed to promote the malignant transformation of breast cancer via multiple signaling pathways, including the Wnt/β-catenin pathway. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has been identified as a CSC-associated Wnt-regulated target gene, but its clinical significance in the context of breast cancer remains elusive. Therefore, the purpose of this study was to investigate the clinical significance of the LGR5-β-catenin axis in breast cancer.

METHODS
Breast cancer tissue blocks from 126 patients were used to construct a tissue microarray (TMA). Histopathological and clinical data including age; tumor size; estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) level; tumor grade; lymph node (LN) status; and survival were obtained from the cancer registry database and patients' medical records. Tissue on the breast TMA was scored for LGR5 and β-catenin expression using semi-quantitative immunohistochemical (IHC) staining. We also analyzed LGR5 expression in cellular datasets available through ONCOMINE, a web-based cancer microarray database.

RESULTS
Immunohistochemical staining revealed that 58 tumors (46%) exhibited high LGR5 expression, whereas 56 tumors (47%) displayed high β-catenin expression. High levels of LGR5 expression were significantly associated with tumor size (p = 0.002), LN metastasis status (p = 0.044), and triple-negative breast cancer (p = 0.029), consistent with our findings from the ONCOMINE database. In addition, we also found that β-catenin -expressing breast cancers were positive correlated with HER2 overexpression. Finally, with respect to clinical outcomes, patients with high levels of LGR5-β-catenin axis expression exhibited poorer relapse-free survival (RFS) compared to patients with low levels of LGR5-β-catenin axis expression (p = 0.027).

CONCLUSION
LGR5 overexpression was significantly associated with high T stage and LN metastasis status. High LGR5 expression was also associated with reduced RFS, indicating that LGR5 may represent a promising prognostic marker for breast cancer patients.

D015972:Gene Expression Regulation, Neoplastic


Smoking Cessation and Adolescent Treatment Response With Comorbid ADHD.

Abstract: Minors entering treatment for alcohol and other drug (AOD) use disorders tend to smoke at high rates, and many have comorbid attention deficit hyperactivity disorder (ADHD). Clear-air laws force patients to refrain from smoking on the premises of AOD treatment facilities, which may hinder the progress of treatment-seeking populations who smoke and struggle with ADHD comorbidity in particular. This study explores clinical characteristics associated with smoking among youths presenting for residential treatment, clinical characteristics associated with smoking cessation, and the impact of smoking cessation with ADHD comorbidity on AOD treatment response. Participants were 195 adolescents (52% female, aged 14-18 years) court-referred to residential treatment. Data were collected at intake, prospectively each week for the 10-week treatment period, and at discharge. Two-thirds (67%) of the enrollment sample entered treatment smoking half a pack a day on average, a large proportion (50%) of which did not smoke during treatment. ADHD patients were more likely to smoke before and during treatment except for those who got active in service and step-work. Quitting smoking did not adversely affect AOD outcomes and was associated with better prognosis of lowered AOD cravings for youths with and without ADHD. Smoking cessation during adolescent AOD treatment is recommended with provision of pharmaceutical and/or behavioral modalities that reduce nicotine withdrawal.

Pagano|Maria E|ME|
Delos-Reyes|Christina M|CM|
Wasilow|Sherry|S|
Svala|Kathleen M|KM|
Kurtz|Steven P|SP|

D001289:Attention Deficit Disorder with Hyperactivity

Smoking cessation
Adolescents
ADHD
Service
Substance abuse treatment


A rise in births following contraceptive failure in France between 2010 and 2016: results from the French national perinatal surveys.

Abstract:
BACKGROUND
In France, while the prevalence of contraception is high, a significant proportion of pregnancies are unintended. Following the 2012 pill scare, the contraceptive method mix, which was mostly comprised of pills and intrauterine devices (IUD), has become more diversified. In this changing landscape, our objective was to describe trends in live births resulting from contraceptive failure and evaluate how patterns of contraceptive use have contributed to observed changes between 2010 and 2016.

METHODS
We used data from the 2010 and the 2016 French National Perinatal surveys which included all births from all maternity units in France over a one-week period. Interviews collecting information about pre-conception contraceptive practices were conducted in the maternity ward post-delivery. Women were classified as having a contraceptive failure if they discontinued contraception because they were pregnant. Our study sample included adult women who had a live birth, had ever used contraception and did not undergo infertility treatment (n = 11,590 in 2010 and n = 9703 in 2016). We evaluated changes in contraceptive failure over time using multivariate Poisson regressions to adjust for sociodemographic characteristics and pre-pregnancy contraceptive methods.

RESULTS
Pre-pregnancy contraception evolved between 2010 and 2016 with a 12.3% point-drop in pill use, and conversely, 4.6%- and 3.2%-point increases in IUD and condom use, respectively. Use of other barrier or natural methods doubled between 2010 and 2016 but remained marginal (1.4% in 2010 vs 3.6% in 2016). Between 2010 and 2016, the proportion of live births resulting from contraceptive failure rose from 7.8 to 10.0%, with higher risks among younger, parous and socially disadvantaged mothers. The risk ratio of contraceptive failure in 2016 compared to 2010 remained higher after sociodemographic adjustments (aRR = 1.34; 95% CI; 1.23-1.47) and after adjusting for pre-pregnancy contraceptive method mix (aRR = 1.35; 95% CI; 1.25-1.49). Increases in contraceptive failures were concentrated among pill and condom users.

CONCLUSIONS
Recent shifts in contraceptive behaviors in France following the 2012 pill scare may be associated with a subsequent increase in births resulting from short acting contraceptives failures.

Contraceptive failure
France
Perinatal survey
Pill scare
Contraceptive behaviors


The critical role of primer pheromones in maintaining insect sociality.

Abstract: Primer pheromones play a pivotal role in the biology and social organization of insect societies. Despite their importance, they have been less studied because of the complexity of the required bioassays and, consequently, only a few of them have been chemically identified to date. The major primer pheromones are that of the queen pheromones that regulate reproductive skew and maintain colony cohesion and function. From a theoretical viewpoint, several features regarding the chemistry of queen pheromones can be predicted. They should be generally nonvolatile in order to avoid saturation of the colony space, which might otherwise hamper their perception because of sensory habituation. Accordingly, they should be actively dispersed throughout the colony by workers. The queen pheromone should also be caste-specific, qualitatively different from any worker pheromone, and preferably multicomponent, to allow unequivocal identification of the queen. The bi-potency of the female larvae in social Hymenoptera to become queen or worker necessitates strict regulation over pheromone production. Indeed, in the honeybee, the biosynthetic pathways as well as the genomic expressions are completely disparate between queens and workers. Future advances in chemical analyses, transcriptomics, proteomics, and metabolomics will enrich our understanding of the chemistry, mechanisms, and crucial role that primer pheromones play in social evolution.

queen pheromones
social behavior
social insects


Taking another's perspective promotes right parieto-frontal activity that reflects open-minded thought.

Abstract: Critical thinking (CT) is important for consensus building. Although the practice of CT using debate is widely used to improve open-minded thought, the cognitive processes underlying this improvement remain poorly understood. Here, functional magnetic resonance imaging (fMRI) was employed to assess how neural responses while considering another's opinion are changed by CT practice and to determine whether the cortical network showing activation changes related to personality traits is relevant to consensus building. A total of 52 healthy participants were divided into three groups for an intervention; the participants read another's reasoning regarding a controversial issue and judged whether this person's viewpoint was affirmative during fMRI measurements. The intervention required them to prepare speech texts from a designated viewpoint based on both themselves and others. Compared to the control group, the group who took another's perspective showed enhanced activation of the right parieto-frontal network, that has been implicated in belief update, cognitive reappraisal of emotion, and self-perspective inhibition. Additionally, activation of the orbitofrontal cortex was negatively correlated with a stubbornness index. The results provide the first neural evidence of the effects of CT practice and support the notion that open-minded thought underlies the benefits of this practice.

Miura|Naoki|N|0000-0001-6676-9734 Sugiura|Motoaki|M| Nozawa|Takayuki|T| Yamamoto|Yuki|Y| Sasaki|Yukako|Y| Hamamoto|Yumi|Y| Yamazaki|Shohei|S| Hirano|Kanan|K| Takahashi|Makoto|M| Kawashima|Ryuta|R|

open-minded thought
critical thinking
fMRI
right parieto-frontal network
debate practice


Nocturia in Patients With Parkinson's Disease.

Abstract:
Background
Waking up from sleep more than once to pass urine, known as nocturia, is an important nonmotor symptom in Parkinson's disease (PD). Very little is known about the cause for nocturia. The aim of this work was to evaluate lower urinary tract (LUT) symptoms in patients with PD reporting nocturia using standardized validated questionnaires and bladder diaries and to assess the impact of nocturia on quality of life and sleep.

Methods
Twenty-three consecutive patients with PD (17 males, 6 females; mean age: 68.5 years; range, 50-85) referred to a specialist uro-neurology clinic reporting nocturia according to the International Continence Society definition were included. Patients measured their daily fluid intake, urinary output per void, and recorded these with the timing of voids on a 3-day bladder diary. Standardized questionnaires were used to assess LUT symptoms (Urinary Symptom Profile, International Prostate Symptom Score, and Qualiveen Short Form) and sleep quality (Parkinson's Disease Sleep Scale).

Results
Mean duration of PD was 10.1 years, and mean severity on H & Y scale was 3.0 (range, 1.0-5.0). Median duration of LUT symptoms was 6.0 years. Mean night-time urinary frequency was 3.5 (range, 1.0-7.3), and mean nocturnal maximum voided volume was 242 mL. Mean Nocturnal Polyuria Index (NPi) was 0.4 (range, 0.13-0.75), and 13 patients (56.5%) had nocturnal polyuria (NPi > 0.33). Patients with nocturnal polyuria reported more-severe LUT symptoms that impacted quality of life and sleep.

Conclusions
In this preliminary study, nocturnal polyuria seems to be common in patients with PD reporting nocturia and appears to affect quality of life and sleep, though this was not statistically significant. The bladder diary is an essential tool in the assessment of nocturia in patients with PD.

Smith|Matthew|M|
Seth|Jai|J|
Batla|Amit|A|
Hofereiter|Johann|J|
Bhatia|Kailash P|KP|
Panicker|Jalesh N|JN|

nocturia
Parkinson's disease
sleep
nocturnal polyuria


Bioconversion of essential oil components of Perilla frutescens by Saccharomyces cerevisiae.

Abstract: The essential oil of perilla (Perilla frutescens) contains volatile low molecular weight compounds such as monoterpenes and phenylpropenes. The composition of the essential oil is classified into about ten chemotypes. The biosynthesis of these constituents is strictly controlled genetically. Among the compounds contained in perilla essential oil, the bioconversion of pure compounds such as perillaldehyde, limonene, and citral has been reported, but that of many other components has not. In addition, changes in the volatile components of raw plant material during brewing have also been investigated for wine and beer. In this study, we examined the bioconversion of perilla essential oil components by Saccharomyces cerevisiae during the brewing of liquor with perilla leaves. S. cerevisiae was added to the ethanol-water extract of dried leaves of P. frutescens and P. citriodora for seven essential oil types: perillaldehyde type, piperitenone type, perillene type, perillaketone type, elsholtziaketone type, citral type, and phenylpropanoid type. Volatile compounds in the reaction mixtures were analyzed by solid-phase microextraction (SPME)-GC-MS, revealing bioconversion of perillaldehyde, isoegomaketone, neral, and geranial by S. cerevisiae. Analysis of the conversion products suggests that they were formed by the reduction of C=C bonds and aldehydes, as well as by esterification and dehydration reactions.

Bioconversion
Perilla frutescens
Saccharomyces cerevisiae
Monoterpenoids
Perillyl alcohol
Trans-shisool


Brain Network to Placebo and Nocebo Responses in Acute Experimental Lower Back Pain: A Multivariate Granger Causality Analysis of fMRI Data.

Abstract: Background and Objective: Placebo and nocebo responses are widely observed. Herein, we investigated the nocebo hyperalgesia and placebo analgesia responses in brain network in acute lower back pain (ALBP) model using multivariate Granger causality analysis (GCA). This approach analyses functional magnetic resonance imaging (fMRI) data for lagged-temporal correlation between different brain areas. Method: After completing the ALBP model, 20 healthy subjects were given two interventions, once during a placebo intervention and once during a nocebo intervention, pseudo-randomly ordered. fMRI scans were performed synchronously during each intervention, and visual analog scale (VAS) scores were collected at the end of each intervention. The fMRI data were then analyzed using multivariate GCA. Results: Our results found statistically significant differences in VAS scores from baseline (pain status) for both placebo and nocebo interventions, as well as between placebo and nocebo interventions. In placebo network, we found a negative lagged-temporal correlation between multiple brain areas, including the dorsolateral prefrontal cortex (DLPFC), secondary somatosensory cortex area, anterior cingulate cortex (ACC), and insular cortex (IC); and a positive lagged-temporal correlation between multiple brain areas, including IC, thalamus, ACC, as well as the supplementary motor area (SMA). In the nocebo network, we also found a positive lagged-temporal correlation between multiple brain areas, including the primary somatosensory cortex area, caudate, DLPFC and SMA. Conclusion: The results of this study suggest that both pain-related network and reward system are involved in placebo and nocebo responses. The placebo response mainly works by activating the reward system and inhibiting pain-related network, while the nocebo response is the opposite. Placebo network also involves the activation of opioid-mediated analgesia system (OMAS) and emotion pathway, while nocebo network involves the deactivation of emotional control. At the same time, through the construction of the GC network, we verified our hypothesis that nocebo and placebo networks share part of the same brain regions, but the two networks also have their own unique structural features.

Shi|Yu|Y| Cui|Shaoye|S| Zeng|Yanyan|Y| Huang|Shimin|S| Cai|Guiyuan|G| Yang|Jianming|J| Wu|Wen|W|

nocebo hyperalgesia
placebo analgesia
GCA
reward system
anxiety
dopamine
opioid


Environmental bottlenecks in children's genetic potential for adult socio-economic attainments: Evidence from a health shock.

Abstract: This paper explores gene-environment interactions-interactions between family environments and children's genetic predispositions-in determining educational attainment. The central question is whether poor childhood family environments reduce children's ability to leverage their genetic gifts to achieve high levels of educational attainment-are there important 'bottlenecks' for poor children? The multigenerational information and genetic data contained in the United States' Health and Retirement Study are used to separate two mechanisms for intergenerational transmission of socio-economic status: genetic endowments and family environments. Using parental in utero exposure to the 1918-19 influenza pandemic as a source of quasi-experimental variation in family environments (that did not affect children's genetic endowments), I estimate interactions between parental investments and children's genetic potential. The main finding suggests that girls with high genetic potential whose fathers were exposed to influenza face reduced educational attainments-a gene-environment interaction-but there is no similar effect for boys.

educational attainment
foetal origins
gene–environment interactions
multigenerational analysis
social mobility