The effect of minimal invasive techniques and physiotherapy on pain and disability in elderly: A retrospective study.

Abstract:
BACKGROUND
Low back pain is one of the major musculoskeletal problems seen in elderly, and it's the fifth common cause for hospitalization.

OBJECTIVE
This retrospective study has determined whether minimal invasive techniques or physiotherapy methods are effective for decreasing pain and improving functions in the geriatric population.

METHODS
A retrospective design was used in this study. Sixty-one patients aged ⩾ 65, who were referred to physiotherapy enrolled in the study. The patients were divided into 2 groups; Group 1 received minimal invasive techniques, whereas Group 2 had no surgery or no minimal invasive application. Pressure Pain Threshold (PPT) was used for perceived pain intensity, Semmes Weinstein Monofilaments (SWM) was used to assess tactile sensitivity, and Oswestry Disability Index (ODI) was used to determine perceived functional disability. Physiotherapy methods including soft tissue mobilizations, muscle-energy techniques and spinal stabilization exercises were used in the treatment of all patients. The outcomes were evaluated pre- and post-physiotherapy applications.

RESULTS
Significant improvements in PPT were shown in both groups after physiotherapy treatment as to baseline (p< 0.05). Despite the significant improvements in PPT values of all muscles in Group 1, Group 2 had significant improvements in PPT except Hamstring muscles (p< 0.05). Functional disability levels of both groups reduced acc. to ODI, improvement in disability scores was only significant in Group 1 (p< 0.05).

CONCLUSION
Although both treatments showed pain relief, functional restoration and improvement in hypoesthesia existence; there was no superiority of physiotherapy alone over physiotherapy added minimal invasive treatments in terms of parameters.

D019060:Minimally Invasive Surgical Procedures

Low back pain
geriatrics
exercise
facet denervation
rehabilitation


Psychopathological constellation in patients with PNES: A new hypothesis.

Abstract: Depression symptoms have often reported in patients with psychogenic nonepileptic seizures (PNES), although the underlying psychopathological symptomatology has been poorly understood. Our aim was to compare constellations of psychological and behavioral disturbance in PNES with respect to patients with mild-major depressive disorder (MDD), hypothesizing that the construct of depression might be different in the two groups. Ten patients with PNES and ten sex-/age-matched patients with mild-MDD newly-diagnosed, were enrolled in this study. A wide neuropsychiatric battery was employed including the following: symptoms checklist 90-R (SCL-90-R), Toronto alexithymia scale (TAS-20), Hamilton anxiety rating scale (HAMA), Beck depression inventory (BDI II), dissociative experiences scale (DES), traumatic experience checklist (TEC), somatoform dissociation questionnaire (SDQ-20), and temperament and character inventory-revised (TCI-R). No significant difference was detected in the large part of psychopathological examination including personality profile between the two groups. However, PNES showed high scores in alexithymia (p=0.02); anxiety (p=0.03), and somatoform symptomatology (p's<0.03) with respect to patients with mild-MDD. Moreover, somatoform symptoms strongly correlated with depression scores in both groups, whereas alexithymia was influenced by high anxiety level only in the group with PNES. No significant relationship was found between traumatic experience (as measured by TEC) and construct of depression. Our proof-of-concept study suggests that patients with PNES are characterized by their inability to verbalize emotions when dealing with anxiety symptoms, therefore expressing them in a somatic dimension. Further researches, including the investigation of the relationship between anxiety status and emotional expression, are warranted to better understand the pathogenesis of PNES.

Martino|Iolanda|I|
Bruni|Antonella|A|
Labate|Angelo|A|
Vasta|Roberta|R|
Cerasa|Antonio|A|
Borzì|Giuseppe|G|
De Fazio|Pasquale|P|
Gambardella|Antonio|A|

D011569:Psychiatric Status Rating Scales

Psychopathology
Psychogenic nonepileptic seizures
Major depressive disorder
Neuropsychiatric assessment


Heparanase Promotes Syndecan-1 Expression to Mediate Fibrillar Collagen and Mammographic Density in Human Breast Tissue Cultured ex vivo.

Abstract: Mammographic density (MD) is a strong and independent factor for breast cancer (BC) risk and is increasingly associated with BC progression. We have previously shown in mice that high MD, which is characterized by the preponderance of a fibrous stroma, facilitates BC xenograft growth and metastasis. This stroma is rich in extracellular matrix (ECM) factors, including heparan sulfate proteoglycans (HSPGs), such as the BC-associated syndecan-1 (SDC1). These proteoglycans tether growth factors, which are released by heparanase (HPSE). MD is positively associated with estrogen exposure and, in cell models, estrogen has been implicated in the upregulation of HPSE, the activity of which promotes SDC expression. Herein we describe a novel measurement approach (single-sided NMR) using a patient-derived explant (PDE) model of normal human (female) mammary tissue cultured ex vivo to investigate the role(s) of HPSE and SDC1 on MD. Relative HSPG gene and protein analyses determined in patient-paired high vs. low MD tissues identified SDC1 and SDC4 as potential mediators of MD. Using the PDE model we demonstrate that HPSE promotes SDC1 rather than SDC4 expression and cleavage, leading to increased MD. In this model system, synstatin (SSTN), an SDC1 inhibitory peptide designed to decouple SDC1-ITGαvβ3 parallel collagen alignment, reduced the abundance of fibrillar collagen as assessed by picrosirius red viewed under polarized light, and reduced MD. Our results reveal a potential role for HPSE in maintaining MD via its direct regulation of SDC1, which in turn physically tethers collagen into aligned fibers characteristic of MD. We propose that inhibitors of HPSE and/or SDC1 may afford an opportunity to reduce MD in high BC risk individuals and reduce MD-associated BC progression in conjunction with established BC therapies.

Huang|Xuan|X|
Reye|Gina|G|
Momot|Konstantin I|KI|
Blick|Tony|T|
Lloyd|Thomas|T|
Tilley|Wayne D|WD|
Hickey|Theresa E|TE|
Snell|Cameron E|CE|
Okolicsanyi|Rachel K|RK|
Haupt|Larisa M|LM|
Ferro|Vito|V|
Thompson|Erik W|EW|
Hugo|Honor J|HJ|

heparanase
syndecan-1
mammographic density
breast cancer
NMR


Gratitude from patients and relatives in palliative care-characteristics and impact: a national survey.

Abstract:
OBJECTIVES
To explore the expressions of gratitude (EoG) received from patients and relatives and their influence on palliative care professionals (PCPs).

METHODS
A national online survey was sent to a representative of PCPs of each service listed in the national directory of palliative care (PC) services (n=272) (ie, hospital PC support team, hospice, paediatrics, etc). The questionnaire was pilot tested with experts. It comprised three sections: the overall perspective of receiving gratitude in the service, the personal experience of its influence and sociodemographic questions. A mailing schedule was designed to enhance the response rate.

RESULTS
186 representatives from all over Spain completed the questionnaire (68% response rate). 79% of service representatives reported that they almost always received EoG. These came mainly from families (93%). These EoG were very often put on display (84%) and shared with other health professionals (HPs) involved in care (45%). EoG evoked positive feelings in the team members. Based on their experience, respondents attributed different functions to these EoG: increased professional satisfaction (89%), a source of support in difficult times (89%), mood improvement, encouragement to continue and rewards for effort (88%). Services, where gratitude was more frequently received, were associated with PCPs who more frequently reported being proud of their work (p=0.039, Pearson's correlation test).

CONCLUSIONS
Gratitude from patients and relatives was frequent and significant to those who work in PC. HPs considered that EoG offer multiple beneficial effects and also a protective role in their practice against distress and an increase in resilience skills.

Gratitude
relatives
palliative care
health professionals
satisfaction
resilience


Bacteria associated with marginal zone lymphomas.

Abstract: In the last decades some bacteria have been associated with a various extent with marginal zone (extra nodal, nodal and splenic types) lymphomas are frequently associated with chronic infections, with important clinical, molecular, biological, and therapeutic implications. The well-known correlation between Helicobacter pylori and gastric MALT-lymphoma, the recently reported links between Chlamydia psittaci and ocular adnexal MALT-lymphoma and Borrelia burgdorferi and cutaneous MALT lymphoma constitute the most studied examples; in addition, Campylobacter jejuni and some more recent associations encompassing Achromobacter xylosoxidans and Haemophilus influenzae will be further reported. Biological and clinical features, therapeutic implications and future perspectives of these lymphoma-microbial associations are discussed in this review.

Ponzoni|Maurilio|M|
Ferreri|Andrés J M|AJ|

Bacteria Lymphoma Infection Helicobacter Chlamydia Borrelia Campylobacter Achromobacter Haemophilus


A novel mutation in the JH4 domain of JAK3 causing severe combined immunodeficiency complicated by vertebral osteomyelitis.

Abstract: JAK3 is a tyrosine kinase essential for signaling downstream of the common gamma chain subunit shared by multiple cytokine receptors. JAK3 deficiency results in T-B+NK- severe combined immune deficiency (SCID). We report a patient with SCID due to a novel mutation in the JAK3 JH4 domain. The function of the JH4 domain remains unknown. This is the first report of a missense mutation in the JAK3 JH4 domain, thereby demonstrating the importance of the JH4 domain of JAK3 in host immunity.

Qamar|Farah|F|
Junejo|Samina|S|
Qureshi|Sonia|S|
Seleman|Michael|M|
Bainter|Wayne|W|
Massaad|Michel|M|
Chou|Janet|J|
Geha|Raif S|RS|


Reconstructive surgery in immunocompromised patients: evaluation and therapy.

Abstract:
BACKGROUND
An increasing number of patients undergoing reconstructive surgery are immunocompromised due to different reasons and different medical treatments. Some of the used immunosuppressive drugs may affect the process of wound healing and thereby, impair the long-term success of surgical treatment. Therefore, this retrospective analysis aimed at the evaluation of the perioperative treatment and surgical outcome of immunocompromised patients undergoing different reconstructive procedures.

METHODS
A retrospective review was performed of 8 immunocompromised patients with different primary diseases who needed reconstructive surgery: 2 patients with non-Hodgkin lymphoma, 1 patient with an acute myeloid leukemia, 1 patient with colitis ulcerosa, 1 patient with liver cirrhosis, 1 patient with chronic polyarthritis, and 2 patients with malignant melanoma.

RESULTS
In 7 of our 8 presented cases, multiple operations with wound debridements have been necessary to optimize the granulation of the wound bed before reconstructive surgery. 3 out of these 7 patients required further operations due to wound dehiscence or necrosis, with 2 of them as a result of increased immunosuppressive therapy. 5 out of 8 patients needed no further surgical treatment.

CONCLUSIONS
Both the perioperative drug therapy and the reconstructive surgery concept need to be determined carefully in each individual case of the immunocompromised patients. Thus, the appropriate point in time of operation to achieve the best possible wound healing as well as the complexity of the procedure will require the consideration of a 'less is more' strategy in selected cases.

Dunda|Sebastian E|SE|
Bozkurt|Ahmet|A|
Pallua|Norbert|N|
Krapohl|Björn Dirk|BD|

reconstructive surgery
immunocompromised patients
plastic surgery


The International Nutrition Care Process and Terminology Implementation Survey: Towards a Global Evaluation Tool to Assess Individual Practitioner Implementation in Multiple Countries and Languages.

Abstract:
BACKGROUND
The Nutrition Care Process (NCP) and NCP Terminology (NCPT) is a systematic framework for critical thinking, decision making, and communication for dietetics practitioners worldwide, aiming to improve quality and patient safety in nutrition care. Although dietetics practitioners in several countries have implemented the NCP/NCPT during recent years, to date there is no globally validated instrument for the evaluation of NCP/NCPT implementation that is available in different languages and applicable across cultures and countries.

OBJECTIVE
The aim of this study was to develop and test a survey instrument in several languages to capture information at different stages of NCP/NCPT implementation across countries and cultures.

SETTING
In this collaboration between dietetics practitioners and researchers from 10 countries, an International NCP/NCPT Implementation Survey tool was developed and tested in a multistep process, building on the experiences from previous surveys. The tool was translated from English into six other languages. It includes four modules and describes demographic information, NCP/NCPT implementation, and related attitudes and knowledge.

METHODS
The survey was reviewed by 42 experts across 10 countries to assess content validity and clarity. After this, 30 dietetics practitioners participated in cognitive interviews while completing the survey. A pilot study was performed with 210 participants, of whom 40 completed the survey twice within a 2- to 3-week interval.

RESULTS
Scale content validity index average was 0.98 and question clarity index was 0.8 to 1.0. Cognitive interviews and comments from experts led to further clarifications of the survey. The repeated pilot test resulted in Krippendorff's α=.75. Subsequently, refinements of the survey were made based on comments submitted by the pilot survey participants.

CONCLUSIONS
The International NCP/NCPT Implementation Survey tool demonstrated excellent content validity and high test-retest reliability in seven different languages and across an international context. This tool will be valuable in future research and evaluation of implementation strategies.

Lövestam|Elin|E|
Vivanti|Angela|A|
Steiber|Alison|A|
Boström|Anne-Marie|AM|
Devine|Amanda|A|
Haughey|Orla|O|
Kiss|Caroline M|CM|
Lang|Nanna R|NR|
Lieffers|Jessica|J|
Lloyd|Lyn|L|
O'Sullivan|Therese A|TA|
Papoutsakis|Constantina|C|
Thoresen|Lene|L|
Orrevall|Ylva|Y|
|||

D004046:Dietetics
D006284:Health Plan Implementation
D006801:Humans
D007802:Language
D044623:Nutrition Therapy
D010865:Pilot Projects
D017064:Process Assessment, Health Care
D015203:Reproducibility of Results
D011795:Surveys and Questionnaires
D009626:Terminology as Topic

Nutrition Care Process and Terminology
Implementation
Survey
Evaluation
Validation


Neighbor-directed histidine N (τ)-alkylation: A route to imidazolium-containing phosphopeptide macrocycles.

Abstract: Our recently discovered, selective, on-resin route to N(τ)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. Interestingly, these cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Neighbor-directed histidine N(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.

Qian|Wen-Jian|WJ|
Park|Jung-Eun|JE|
Grant|Robert|R|
Lai|Christopher C|CC|
Kelley|James A|JA|
Yaffe|Michael B|MB|
Lee|Kyung S|KS|
Burke|Terrence R|TR|

Plk1
cationic dialkyl histidine
crystal structure
peptide macrocycles, phosphopeptides
polo kinase
polo-box domain


Spectrum of mucin-producing neoplastic conditions of the abdomen and pelvis: cross-sectional imaging evaluation.

Abstract: Various mucin-producing neoplasms originate in different abdominal and pelvic organs. Mucinous neoplasms differ from non-mucinous neoplasms because of the differences in clinical outcome and imaging appearance. Mucinous carcinoma, in which at least 50% of the tumor is composed of large pools of extracellular mucin and columns of malignant cells, is associated with a worse prognosis. Signet ring cell carcinoma is characterized by large intracytoplasmic mucin vacuoles that expand in the malignant cells with the nucleus displaced to the periphery. Its prognosis is also generally poor. In contrast, intraductal papillary mucinous neoplasm of the bile duct and pancreas, which is characterized by proliferation of ductal epithelium and variable mucin production, has a better prognosis than other malignancies in the pancreaticobiliary tree. Imaging modalities play a critical role in differentiating mucinous from non-mucinous neoplasms. Due to high water content, mucin has a similar appearance to water on ultrasound (US), computed tomography (CT), and magnetic resonance imaging, except when thick and proteinaceous, and then it tends to be hypoechoic with fine internal echoes or have complex echogenicity on US, hyperdense on CT, and hyperintense on T1- and hypointense on T2-weighted images, compared to water. Therefore, knowledge of characteristic mucin imaging features is helpful to diagnose various mucin-producing neoplastic conditions and to facilitate appropriate treatment.

Lee|Nam Kyung|NK|
Kim|Suk|S|
Kim|Hyun Sung|HS|
Jeon|Tae Yong|TY|
Kim|Gwang Ha|GH|
Kim|Dong Uk|DU|
Park|Do Youn|DY|
Kim|Tae Un|TU|
Kang|Dae Hwan|DH|

Abdomen and pelvis
Neoplasm
Mucin
Ultrasound
Computed tomography
Magnetic resonance


Human umbilical cord mesenchymal stem cell transplantation restores hematopoiesis in acute radiation disease.

Abstract:
OBJECTIVE
Nuclear technology has been widely used in military and civilian fields, and radiotherapy is an effective and common form of treatment for cancer. However, acute radiation disease caused by high doses of radiation is a serious complication. The aim of this study was to investigate the chance of mitigating radiation-triggered hematopoiesis failure using human umbilical cord mesenchymal stem cell (HUCMSC) transplantation.

METHODS
Umbilical cords were obtained from three full-term female neonatus through cesarean section at Xinqiao Hospital. Bone marrow mesenchymal stem cells (BMSCs) were cultivated as depicted before. Briefly, monocytes were collected from bone marrow blood by means of density separation columns. An acute radiation disease mouse model was established to compare the restoration effect of HUCMSCs and BMSCs transplanted via the tail vein. The hematopoietic stem cell transplantation (HSCT) mouse model was obtained through bone marrow cell transplantation (BMCT) from C57BL/6 mice (H-2b, donor) to female CB6F1 mice (H-2b×d, recipient) after irradiation. The mice were divided into five groups, including control (saline), irradiated (radiation), bone marrow (HSCT, transplanted 1×106 BM cells), HUCMSC (transplanted a mixture of 1×106 HUCMSCs and 1×106 BM cells), and BMSC group (transplanted a mixture of 1×106 BMSCs and 1×106 BM cells). The blood condition results were used to test the radiation-induced inflammatory reaction, and bone marrow pathological staining (H&E) was used to determine the radiation-induced bone marrow hematopoiesis failure.

RESULTS
After radiation, HUCMSC transplantation significantly improved the survival rate. By analyzing the blood condition test, colony formation, and bone marrow pathology, it was found that the HUCMSC group demonstrated significant functional improvements in terms of the recovery from hematopoiesis failure and reduction of inflammatory reaction.

CONCLUSIONS
HUCMSCs have more advantages over BMSCs in restoring and promoting the recovery of radiation-induced hematopoietic damage, thus having a new therapeutic potential for patients with acute radiation disease.

Yang|Shi-Jie|SJ| Wang|Xiao-Qi|XQ| Jia|Yan-Hui|YH| Wang|Rui|R| Cao|Ke|K| Zhang|Xi|X| Zhong|Jiangfan|J| Tan|Dong-Mei|DM| Tan|Yi|Y|

Acute radiation disease
hematopoiesis failure
HUCMSC


Are There Long-Run Effects of the Minimum Wage?

Abstract: An empirical consensus suggests that there are small employment effects of minimum wage increases. This paper argues that these are short-run elasticities. Long-run elasticities, which may differ from short-run elasticities, are policy relevant. This paper develops a dynamic industry equilibrium model of labor demand. The model makes two points. First, long-run regressions have been misinterpreted because even if the short- and long-run employment elasticities differ, standard methods would not detect a difference using US variation. Second, the model offers a reconciliation of the small estimated short-run employment effects with the commonly found pass-through of minimum wage increases to product prices.

minimum wages
Labor demand
dynamic models
putty-clay


Inhibition of lipolysis: A novel explanation for the hypothermic actions of acetaminophen in non-febrile rodents.

Abstract: Acetaminophen is both widely used to treat children with fever and is also responsible for thousands being hospitalised annually. Historically the antipyretic actions of acetaminophen were attributed to the inhibition of cyclooxygenase (COX-1/2) enzymes and more recently a novel COX-1 variant (COX-3) located in the brain. However, the evidence for acetaminophen-mediated COX inhibition remains contentious. This study assesses the impact of acetaminophen and other putative COX-3 inhibitors on the release of fatty acids during lipolysis as an alternative mechanism by which antipyretics can reduce body temperature during fever. 3T3-L1 adipocytes, primary brown adipocytes and isolated mitochondria were exposed to COX-3 inhibitors and lipolysis and mitochondrial electron transport chain function assessed. Acetaminophen, aminopyrine and antipyrine at 1-10 mM caused a significant decrease (up to 70%; P < 0.01, from control) in lipolysis within 1, 3 and 24 h without affecting cell viability. The inhibition was observed regardless of where along its signalling pathway lipolysis was stimulated. All three compounds were found to significantly attenuate mitochondrial function by up to 30% for complex I and 40% for complex II (P < 0.01, from control). These novel observations combined with the known limited inhibition of the COX enzymes by acetaminophen suggest both the antipyretic and hypothermia induced by acetaminophen and related compounds could be attributed to the direct inhibition of lipolysis and mitochondrial function, rather than cyclooxygenase inhibition centrally. Further these observations could provide new drug targets for reducing fever with the added bonus of fewer individuals being hospitalized by accidental acetaminophen overdose.

Bashir|Shazma|S|
Elegunde|Busayo|B|
Morgan|Winston A|WA|

D015124:8-Bromo Cyclic Adenosine Monophosphate

Lipolysis
Acetaminophen
Cyclooxygenase
Mitochondria
Electron transport chain
Hypothermia


A de novo variant in ADGRL2 suggests a novel mechanism underlying the previously undescribed association of extreme microcephaly with severely reduced sulcation and rhombencephalosynapsis.

Abstract: Extreme microcephaly and rhombencephalosynapsis represent unusual pathological conditions, each of which occurs in isolation or in association with various other cerebral and or extracerebral anomalies. Unlike microcephaly for which several disease-causing genes have been identified with different modes of inheritance, the molecular bases of rhombencephalosynapsis remain unknown and rhombencephalosynapsis presents mainly as a sporadic condition consistent with de novo dominant variations. We report for the first time the association of extreme microcephaly with almost no sulcation and rhombencephalosynapsis in a fœtus for which comparative patient-parent exome sequencing strategy revealed a heterozygous de novo missense variant in the ADGRL2 gene. ADGRL2 encodes latrophilin 2, an adhesion G-protein-coupled receptor whose exogenous ligand is α-latrotoxin. Adgrl2 immunohistochemistry and in situ hybridization revealed expression in the telencephalon, mesencephalon and rhombencephalon of mouse and chicken embryos. In human brain embryos and fœtuses, Adgrl2 immunoreactivity was observed in the hemispheric and cerebellar germinal zones, the cortical plate, basal ganglia, pons and cerebellar cortex. Microfluorimetry experiments evaluating intracellular calcium release in response to α-latrotoxin binding showed significantly reduced cytosolic calcium release in the fœtus amniocytes vs amniocytes from age-matched control fœtuses and in HeLa cells transfected with mutant ADGRL2 cDNA vs wild-type construct. Embryonic lethality was also observed in constitutive Adgrl2-/- mice. In Adgrl2+/- mice, MRI studies revealed microcephaly and vermis hypoplasia. Cell adhesion and wound healing assays demonstrated that the variation increased cell adhesion properties and reduced cell motility. Furthermore, HeLa cells overexpressing mutant ADGRL2 displayed a highly developed cytoplasmic F-actin network related to cytoskeletal dynamic modulation. ADGRL2 is the first gene identified as being responsible for extreme microcephaly with rhombencephalosynapsis. Increased cell adhesion, reduced cell motility and cytoskeletal dynamic alterations induced by the variant therefore represent a new mechanism responsible for microcephaly.

D018507:Gene Expression Regulation, Developmental

ADGRL2
Rhombencephalosynapsis
Adhesion-GPCR
Alpha-latrotoxin
Human extreme microcephaly
LPHN2


Genome shuffling and high-throughput screening of Brevibacterium flavum MDV1 for enhanced L-valine production.

Abstract: L-valine is an essential branched-amino acid that is widely used in multiple areas such as pharmaceuticals and special dietary products and its use is increasing. As the world market for L-valine grows rapidly, there is an increasing interest to develop an efficient L-valine-producing strain. In this study, a simple, sensitive, efficient, and consistent screening procedure termed 96 well plate-PC-HPLC (96-PH) was developed for the rapid identification of high-yield L-valine strains to replace the traditional L-valine assay. L-valine production by Brevibacterium flavum MDV1 was increased by genome shuffling. The starting strains were obtained using ultraviolet (UV) irradiation and binary ethylenimine treatment followed by preparation of protoplasts, UV irradiation inactivation, multi-cell fusion, and fusion of the inactivated protoplasts to produce positive colonies. After two rounds of genome shuffling and the 96-PH method, six L-valine high-yielding mutants were selected. One genetically stable mutant (MDVR2-21) showed an L-valine yield of 30.1 g/L during shake flask fermentation, 6.8-fold higher than that of MDV1. Under fed-batch conditions in a 30 L automated fermentor, MDVR2-21 accumulated 70.1 g/L of L-valine (0.598 mol L-valine per mole of glucose; 38.9% glucose conversion rate). During large-scale fermentation using a 120 m3 fermentor, this strain produced > 66.8 g/L L-valine (36.5% glucose conversion rate), reflecting a very productive and stable industrial enrichment fermentation effect. Genome shuffling is an efficient technique to improve production of L-valine by B. flavum MDV1. Screening using 96-PH is very economical, rapid, efficient, and well-suited for high-throughput screening.

Huang|Qin-Geng|QG| Zeng|Bang-Ding|BD| Liang|Ling|L| Wu|Song-Gang|SG| Huang|Jian-Zhong|JZ|

Genome shuffling
High-throughput screening
Brevibacterium flavum
L-valine
Fermentation


Direct acting antivirals failure: cause and retreatment options.

Abstract: Chronic hepatitis C (HCV) infection is a systemic life-threatening condition that can lead to hepatic and extra-hepatic complications. Sustained virological response (SVR) is associated with a regression of most liver and non-liver manifestations, which reduce mortality. The history of HCV infection therapy radically changed in the last decade, with the introduction of the first generation direct acting antivirals (DAAs). Areas covered: The new regimens, based on the combination of 2 or 3 second-generation DAAs, allow SVR, namely hepatitis C infection cure, in more than 95% of cases. Antiviral treatment is generally well tolerated and its duration (8-16 weeks) varies depending on the stage of liver fibrosis, HCV genotype, prior treatment, baseline viral load, presence of resistance-associated variants (RAV). This review evaluates the cause, the efficacy and safety results in case of DAAs failure. Expert commentary: Despite the excellent efficacy of DAAs, a minority of patients (4-5%) still fail to eradicate HCV, mainly related to poor adherence but also to relapse or viral breakthrough. The main causes of a failure of DAAs are the presence of advanced liver disease, suboptimal treatment and NS5A mutations. Many questions regarding resistant associated substitutions (RASs) prevalence and clinical relevance in re-treatment remain unanswered.

D000998:Antiviral Agents
D024882:Drug Resistance, Viral
D005838:Genotype
D016174:Hepacivirus
D019698:Hepatitis C, Chronic
D006801:Humans
D055118:Medication Adherence
D019233:Retreatment
D012307:Risk Factors
D000072230:Sustained Virologic Response
D017211:Treatment Failure
D019562:Viral Load

Chronic hepatitis C (HCV)
sustained virological response (SVR)
direct acting antivirals (DAAs)
DAAs failure


New photostable naphthalimide-based fluorescent probe for mitochondrial imaging and tracking.

Abstract: Monitoring mitochondria morphological changes temporally and spatially exhibits significant importance for diagnosing, preventing and treating various diseases related to mitochondrial dysfunction. However, the application of commercially available mitochondria trackers is limited due to their poor photostability. To overcome these disadvantages, we designed and synthesized a mitochondria-localized fluorescent probe by conjugating 1,8-naphthalimide with triphenylphosphonium (i.e. NPA-TPP). The structure and characteristic of NPA-TPP was characterized by UV-vis, fluorescence spectroscopy, (1)HNMR, (13)CNMR, FTIR, MS, etc. The photostability and cell imaging were performed on the laser scanning confocal microscopy. Moreover, the cytotoxicity of NPA-TPP on cells was evaluated using (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The results showed that NPA-TPP not only has high sensitivity and specificity to mitochondria, but also exhibits super-high photostability, negligible cytotoxicity and good water solubility. In short, NPA-TPP indicates great potential for targeting mitochondria and enables a real-time and long-term tracking mitochondrial dynamics changes.

Huang|Saipeng|S| Han|Rongcheng|R| Zhuang|Qianfen|Q| Du|Libo|L| Jia|Hongying|H| Liu|Yangping|Y| Liu|Yang|Y|

Photostability
Fluorescent probe
Mitochondrial imaging
1,8-naphthalimides
Real-time tracking


The Anti-Nociceptive Potential of Tulathromycin against Chemically and Thermally Induced Pain in Mice.

Abstract: The present study was conducted to evaluate the analgesic potential of the new triamilide macrolide antibiotic, tulathromycin, at 20 and 40 mg/kg of body weight (BW), subcutaneously against acute pain in mice. Acute pain was induced either chemically (using acetic acid-induced writhing and formalin-induced pain tests) or thermally (using hot-plate, and tail-flick tests). In the acetic acid-induced writhing test, tulathromycin induced a dose-dependent and significant decrease in the number of writhes compared with the control group. In the late phase of the formalin test, a significant decline in hind paw licking time compared with the control group was observed. In the hot-plate and tail-flick tests, tulathromycin caused a dose-dependent and significant prolongation of latency of nociceptive response to heat stimuli, compared with the control group. These findings may indicate that tulathromycin possesses significant peripheral and central analgesic potentials that may be valuable in symptomatic relief of pain, in addition to its well-established antibacterial effect.

anti-nociceptive tulathromycin pain analgesic macrolides


Multiple alternative substrate kinetics.

Abstract: The specificity of enzymes for their respective substrates has been a focal point of enzyme kinetics since the initial characterization of metabolic chemistry. Various processes to quantify an enzyme's specificity using kinetics have been utilized over the decades. Fersht's definition of the ratio kcat/Km for two different substrates as the "specificity constant" (ref [7]), based on the premise that the important specificity existed when the substrates were competing in the same reaction, has become a consensus standard for enzymes obeying Michaelis-Menten kinetics. The expansion of the theory for the determination of the relative specificity constants for a very large number of competing substrates, e.g. those present in a combinatorial library, in a single reaction mixture has been developed in this contribution. The ratio of kcat/Km for isotopologs has also become a standard in mechanistic enzymology where kinetic isotope effects have been measured by the development of internal competition experiments with extreme precision. This contribution extends the theory of kinetic isotope effects to internal competition between three isotopologs present at non-tracer concentrations in the same reaction mix. This article is part of a special issue titled: Enzyme Transition States from Theory and Experiment.

Alternate substrate
Alternate substrate
Enzyme kinetics
Specificity constant
Combinatorial library
Kinetic isotope effects
Internal competition
Alternative substrate
Enzyme specificity


First molecular detection of Rickettsia africae in a tropical bont tick, Amblyomma variegatum, collected in Corsica, France.

Abstract: Here we report the first detection of Amblyomma variegatum, a tick species of medical and veterinary importance, and the first molecular evidence of a pathogen, Rickettsia africae, both new to Corsica (France). In August 2018, an ixodid tick with an unusual morphology was removed from the ventral part of a cow's whole skin in a slaughterhouse located in the village of Ponte-Leccia (Haute-Corse). The tick was morphologically identified as an adult male of A. variegatum. This result was confirmed by 16S rDNA sequence analysis with a close relative being a sequence from Senegal showing 99% nucleotide identity. We tested the tick for Ehrlichia and Rickettsia. The tick was positive to Rickettsia and the corresponding sequence matched with R. africae. There is little or no risk of the introduction and establishment of a viable population of A. variegatum in Corsica by migrating birds. However, if it did, it could produce major economic losses for livestock production. Further studies and sustained surveillance are indicated, not only focusing on this species of tick and this rickettsia, but also on other microorganisms of veterinary and medical importance that might be transmitted in Corsica and other Mediterranean islands.

Rickettsia africae
Amblyomma variegatum
Corsica
Cattle
Mediteranean basin


Genomic rearrangements and the evolution of clusters of locally adaptive loci.

Abstract: Numerous studies of ecological genetics have found that alleles contributing to local adaptation sometimes cluster together, forming "genomic islands of divergence." Divergence hitchhiking theory posits that these clusters evolve by the preferential establishment of tightly linked locally adapted mutations, because such linkage reduces the rate that recombination breaks up locally favorable combinations of alleles. Here, I use calculations based on previously developed analytical models of divergence hitchhiking to show that very few clustered mutations should be expected in a single bout of adaptation, relative to the number of unlinked mutations, suggesting that divergence hitchhiking theory alone may often be insufficient to explain empirical observations. Using individual-based simulations that allow for the transposition of a single genetic locus from one position on a chromosome to another, I then show that tight clustering of the loci involved in local adaptation tends to evolve on biologically realistic time scales. These results suggest that genomic rearrangements may often be an important component of local adaptation and the evolution of genomic islands of divergence. More generally, these results suggest that genomic architecture and functional neighborhoods of genes may be actively shaped by natural selection in heterogeneous environments. Because small-scale changes in gene order are relatively common in some taxa, comparative genomic studies could be coupled with studies of adaptation to explore how commonly such rearrangements are involved in local adaptation.

D000483:Alleles
D016000:Cluster Analysis
D003198:Computer Simulation
D004463:Ecology
D019143:Evolution, Molecular
D015321:Gene Rearrangement
D008040:Genetic Linkage
D056426:Genetic Loci
D014644:Genetic Variation
D005828:Genetics, Population
D044404:Genomic Islands
D008957:Models, Genetic
D009154:Mutation
D011995:Recombination, Genetic
D012641:Selection, Genetic

chromosomal rearrangement
genetic architecture
migration–selection balance
synteny


Diagnostic value of quantitative MP-IgG for Mycoplasma pneumoniae pneumonia in adults.

Abstract: The passive particle agglutination (PA) test, once widely used for Mycoplasma pneumoniae (M. pneumoniae) antibody detection, has gradually been replaced by quantitative enzyme-linked immunosorbent assays (ELISA). However, the lack of diagnostic criteria for quantitative ELISA M. pneumoniae-IgG (MP-IgG) and the low positive rates of ELISA M. pneumoniae-IgM (MP-IgM) limit the diagnostic value of ELISA for M. pneumoniae infection in adults. Here, the diagnostic value of quantitative ELISA MP-IgG was evaluated in adults with Mycoplasma pneumoniae pneumonia (MPP). The serum M. pneumoniae antibodies were detected in 162 patients with MPP, 228 patients with community-acquired pneumonia (CAP) with non-Mycoplasma pneumoniae (NMP), and 162 healthy controls by ELISA, using the PA results as the reference standards. For the MP-IgM-/IgG+ subgroup, a single serum MP-IgG level of ≥92.67 RU/mL can be used as a reference criterion for the diagnosis of acute M. pneumoniae infection. At admission, for patients with CAP, the sensitivity and specificity of ELISA MP-IgM positivity for MPP were 18.51% and 99.56%, respectively. MP-IgM positivity combined with MP-IgG ≥ 92.67 RU/mL increased the sensitivity to 40.12% and decreased the specificity to 94.29%. For paired serum samples obtained within seven days, an ELISA MP-IgG concentration change of ≥1.48-fold and MP-IgG ≥ 92.67 RU/mL on day 7 were used as the diagnostic criteria for M. pneumoniae infection. Accordingly, the combination of qualitative MP-IgM detection and quantitative MP-IgG detection by ELISA is valuable for acute MPP diagnosis in adults.

Wu|Lina|L| Ye|Maosheng|M| Qin|Xiaosong|X| Liu|Yong|Y| Lv|Zhe|Z| Zheng|Rui|R|

Mycoplasma pneumoniae
Enzyme-linked immunosorbent assay
IgG
IgM
Passive particle agglutination test


Protective effects of Panax notoginseng saponins on PME-Induced nephrotoxicity in mice.

Abstract: Polymyxin E (PME) plays an important role in fighting against Gram-negative bacterial infections; however, it causes nephrotoxicity, which limits its clinical use. The aim of this study was to investigate the protective effects of a plant extract Panax notoginseng saponins (PNS) on PME-induced nephrotoxicity in mice. In vivo studies showed that PNS significantly reduced blood urea nitrogen (BUN), serum creatinine (CRE) and number of apoptotic cells in kidney, as well as renal histopathological damage which increased in the presence of PME, and suppressed PME-induced oxidative stress in kidney, as shown by the up-regulation of superoxide dismutase (SOD) and the down-regulation of malondialdehyde (MDA) levels. Furthermore, PNS inhibited the expression of Bax, while increased the expression of Bcl-2 compared to the PME-treated group. In vitro studies showed that PNS decreased intracellular reactive oxygen species (ROS) and MDA levels, increased glutathione (GSH) levels, and enhanced the activity of SOD and glutathione peroxidase (GSH-Px) in murine renal tubular epithelial cells (TCMK-1 cells). In addition, PNS enhanced cell viability and the expression of Bcl-2, restored the mitochondrial membrane potential, inhibited the expression of Bax, inhibited the activity of caspase-3 and caspase-9, and reduce apoptotic rate in PME-treated TCMK-1 cells. PNS could reduce PME-induced nephrotoxicity. The protective effects could result from inhibition of oxidative stress, and prevention of cell apoptosis via the mitochondrial pathway. These findings highlight the potential of PNS as a safe adjunct for ameliorating the nephrotoxicity.

Zhang|Yong|Y| Chi|Xiaoqing|X| Wang|Zizengchen|Z| Bi|Shicheng|S| Wang|Yuemin|Y| Shi|Fushan|F| Hu|Songhua|S| Wang|Huanan|H|

Nephrotoxicity
Polymyxin E (PME)
Panax notoginseng saponins (PNS)
Oxidative stress
Apoptosis


Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson's disease applied retrospectively in a large cohort study of recent onset cases.

Abstract:
OBJECTIVE
To examine the utility of the new Movement Disorder Society (MDS) diagnostic criteria in a large cohort of Parkinson's disease (PD) patients.

METHODS
Recently diagnosed (<3.5 years) PD cases fulfilling United Kingdom (UK) brain bank criteria in Tracking Parkinson's, a UK multicenter prospective natural history study were assessed by retrospective application of the MDS criteria.

RESULTS
In 2000 cases, 1835 (91.7%) met MDS criteria for PD, either clinically established (n = 1261, 63.1%) or clinically probable (n = 574, 28.7%), leaving 165 (8.3%) not fulfilling criteria. Clinically established cases were significantly more likely to have limb rest tremor (89.3%), a good l-dopa response (79.5%), and olfactory loss (71.1%), than clinically probable cases (60.6%, 44.4%, and 34.5% respectively), but differences between probable PD and 'not PD' cases were less evident. In cases not fulfilling criteria, the mean MDS UPDRS3 score (25.1, SD 13.2) was significantly higher than in probable PD (22.3, SD 12.7, p = 0.016) but not established PD (22.9, SD 12.0, p = 0.066). The l-dopa equivalent daily dose of 341 mg (SD 261) in non-PD cases was significantly higher than in probable PD (250 mg, SD 214, p < 0.001) and established PD (308 mg, SD 199, p = 0.025). After 30 months' follow-up, 89.5% of clinically established cases at baseline remained as PD (established/probable), and 86.9% of those categorized as clinically probable at baseline remained as PD (established/probable). Cases not fulfilling PD criteria had more severe parkinsonism, in particular relating to postural instability, gait problems, and cognitive impairment.

CONCLUSION
Over 90% of cases clinically diagnosed as early PD fulfilled the MDS criteria for PD. Those not fulfilling criteria may have an atypical parkinsonian disorder or secondary parkinsonism that is not correctly identified by the UK Brain Bank criteria, but possibly by the new criteria.

Malek|Naveed|N|
Lawton|Michael A|MA|
Grosset|Katherine A|KA|
Bajaj|Nin|N|
Barker|Roger A|RA|
Ben-Shlomo|Yoav|Y|
Burn|David J|DJ|
Foltynie|Tom|T|
Hardy|John|J|
Morris|Huw R|HR|
Williams|Nigel M|NM|
Wood|Nicholas|N|
Grosset|Donald G|DG|
|||

Criteria
Parkinson's disease
Diagnosis
Phenotype


The Cancer Epigenome: Exploiting Its Vulnerabilities for Immunotherapy.

Abstract: During cancer initiation and progression, the somatic epigenome is broadly reprogrammed. This reprogramming can be a consequence of several processes, including altered transcriptional profiles and mutations. In addition, immune cells infiltrating the tumor microenvironment display a reprogrammed epigenome. For instance, tumor infiltrating T cells frequently exhibit an exhausted phenotype characterized by aberrant DNA methylation. Moreover, these aberrant epigenomes of cancer cells and infiltrating immune cells may represent a cancer vulnerability. Accumulating evidence supports the potential of using epigenetic therapy to not only reactivate silenced genes in cancer cells, but to also increase antitumor immunogenicity, by reactivation of endogenous retroviruses, to increase tumor immune-infiltration, and to reinvigorate T cell exhaustion. These findings highlight the potential synergies between epigenetic therapies and immunotherapy.

Loo Yau|Helen|H|
Ettayebi|Ilias|I|
De Carvalho|Daniel D|DD|

immunotherapy
DNA methylation
epigenetic therapy
cancer therapy


Hydroxylamine Derivatives as Nitrogen-Radical Precursors in Visible-Light Photochemistry.

Abstract: In recent years, hydroxylamines derivatives have been exploited as nitrogen-radical precursors in visible-light photochemistry. Their ability to serve as electrophores in redox chemistry has propelled the development of many novel transformations. Fundamental mechanistic aspects as well as the importance in the preparation of nitrogen-containing molecules will be highlighted.

hydroxylamine derivatives
nitrogen radicals
photoredox catalysis
single-electron transfer
visible light


The impact of work culture on quality of care in nursing homes--a review study.

Abstract:
AIM
The main aim of this review study was to identify which factors that characterise the relationship between work culture and quality of care in nursing homes.

METHOD
This review study was structured through systematic search methods to identify articles that describe the relationship between work culture and quality of care in nursing homes. The database search yielded 14510 hits. Closer examination showed that 10401 of these hits were duplicates. Of the remaining 4109 articles, only 10 were related to our aim for the study. A qualitative method were used to explain and understand phenomena of work culture and quality if care in nursing homes.

FINDINGS
Nine out of 10 articles in this review study emphasise the importance of leadership style and supportive management to increase quality of care in nursing homes. Increased empowerment, participation and influence were important factors for improving quality of care. Significant associations between work culture and quality of care and between empowerment and quality of care were reported.

CONCLUSION
Nursing management and leaders must take in consideration that work culture is crucial for improving quality of care in nursing homes, and this study can be used to increase the focus on the work culture among healthcare personnel in nursing homes. Changes are necessary to increase healthcare personnel's job satisfaction, empowerment, autonomy and influence in nursing homes. Giving empowerment to the healthcare personnel working in nursing homes is both an organisational and an interpersonal issue. Being given empowerment and influence over their own work situation, the healthcare workers can be more committed and involved in the goal of obtaining best possible care to the residents.

André|Beate|B|
Sjøvold|Endre|E|
Rannestad|Toril|T|
Ringdal|Gerd I|GI|

work culture
nursing homes and quality of care
work climate


Secondary sclerosing cholangitis as a complication of severe COVID-19: A case report and review of the literature.

Abstract: This case of secondary sclerosing cholangitis (SSC-CIP) emphasizes the need to provide follow-up care for patients that have recovered from COVID-19 in order to understand the complexity of SARS-CoV-2 associated sequela.

secondary sclerosing cholangitis
COVID‐19
SARS‐CoV‐2
biliary epithelium
cholangiopathy
liver injury


Evaluation of the accuracy of the CyberKnife Synchrony™ Respiratory Tracking System using a plastic scintillator.

Abstract:
PURPOSE
The Synchrony™ Respiratory Tracking System of the CyberKnife® Robotic Radiosurgery System (Accuray, Inc., Sunnyvale, CA, USA) enables real-time tracking of moving targets such as lung and liver tumors during radiotherapy. Although film measurements have been used for quality assurance of the tracking system, they cannot evaluate the temporal tracking accuracy. We have developed a verification system using a plastic scintillator that can evaluate the temporal accuracy of the CyberKnife Synchrony.

METHODS
A phantom consisting of a U-shaped plastic frame with three fiducial markers was used. The phantom was moved on a plastic scintillator plate. To identify the phantom position on the recording video in darkness, four pieces of fluorescent tape representing the corners of a 10 cm × 10 cm square around an 8 cm × 8 cm window were attached to the phantom. For a stable respiration model, the phantom was moved with the fourth power of a sinusoidal wave with breathing cycles of 4, 3, and 2 s and an amplitude of 1 cm. To simulate irregular breathing, the respiratory cycle was varied with Gaussian random numbers. A virtual target was generated at the center of the fluorescent markers using the MultiPlan™ treatment planning system. Photon beams were irradiated using a fiducial tracking technique. In a dark room, the fluorescent light of the markers and the scintillation light of the beam position were recorded using a camera. For each video frame, a homography matrix was calculated from the four fluorescent marker positions, and the beam position derived from the scintillation light was corrected. To correct the displacement of the beam position due to oblique irradiation angles and other systematic measurement errors, offset values were derived from measurements with the phantom held stationary.

RESULTS
The average SDs of beam position measured without phantom motion were 0.16 and 0.20 mm for lateral and longitudinal directions, respectively. For the stable respiration model, the tracking errors (mean ± SD) were 0.40 ± 0.64 mm, -0.07 ± 0.79 mm, and 0.45 ± 1.14 mm for breathing cycles of 4, 3, and 2 s, respectively. The tracking errors showed significant linear correlation with the phantom velocity. The correlation coefficients were 0.897, 0.913, and 0.957 for breathing cycles of 4, 3, and 2 s, respectively. The unstable respiration model also showed linear correlation between tracking errors and phantom velocity. The probability of tracking error incidents increased with decreasing length of the respiratory cycles. Although the tracking error incidents increased with larger variations in respiratory cycle, the effect on the cumulative probability was insignificant. For a respiratory cycle of 4 s, the maximum tracking error was 1.10 and 1.43 mm at the probability of 10% and 5%, respectively. Large tracking errors were observed when there was phase shift between the tumor and the LED marker.

CONCLUSION
This technique allows evaluation of the motion tracking accuracy of the Synchrony™ system over time by measurement of the photon beam. The velocity of the target and phase shift have significant effects on accuracy.

Akino|Yuichi|Y| Sumida|Iori|I| Shiomi|Hiroya|H| Higashinaka|Naokazu|N| Murashima|Yoshiichi|Y| Hayashida|Miori|M| Mabuchi|Nobuhisa|N| Ogawa|Kazuhiko|K|

CyberKnife
plastic scintillator
motion tracking
respiratory motion


Sodium alginate templated hydroxyapatite/calcium silicate composite adsorbents for efficient dye removal from polluted water.

Abstract: In this work, natural polysaccharide product sodium alginate (SA) served as templates to prepare porous calcium silicate (CS) hydroxyapatite (HA) composite microspheres (CHCM) with high specific surface area by a new route combining ion exchange and calcination. CHCM played an important role in the fields of environmental protection with its large specific surface area, excellent adsorptive property, high mechanical strength and good regeneration performance. In order to explore its treatment capacity of wastewater, a series of eriochromeblue black R (EBBR) adsorption experiments were carried out. The equilibrium data fitted well with the Langmuir isotherm with a maximum adsorption capacity of 76.80 mg/g. Electrostatic interaction, ionic bonds and physical adsorption were responsible for the interactions between the EBBR and CHCM. Meanwhile, the CHCM maintained complete spherical and almost undamaged in the regeneration experiments, which confirmed its stability for cyclical usage. This paper demonstrates the role of natural polysaccharide product sodium alginate serving as templates to prepare useful products with potential wide applications.

You|Yue|Y| KeqiQu||| Huang|Zhanhua|Z| Ma|Rongxiu|R| Shi|Cai|C| Li|Xiang|X| Liu|Daqing|D| Dong|Mengyao|M| Guo|Zhanhu|Z|

Sodium alginate
Hydroxyapatite
Porous composite adsorbents


Spontaneous rupture of a hybrid oncocytic chromophobe tumor: A case report.

Abstract: The prognosis of Hybrid oncocytic chromophobe tumor (HOCT) is usually excellent, nevertheless, we are reporting a rare case of HOCT that resulted in death from tumor infection and rupture. Bilateral solid and cystic masses were detected in a 55-year-old woman during a computed tomography examination. HOCT was diagnosed following histopathological examination obtained during needle biopsy. Watchful waiting at another hospital was selected as the treatment strategy. Three years later, she was referred to our hospital in shock and died on the 3rd hospital day. The cause of death was thought to be peritonitis secondary to rupture of an infected HOCT.

Matsuoka|Yuki|Y| Matsuda|Yoko|Y| Arai|Hironobu|H| Sugimoto|Mikio|M|

Spontaneous rupture
Hybrid oncocytic chromophobe tumor
Autopsy


What the nonneurologist can do to treat headache.

Abstract: Nonneurologists who treat patients with headaches should be able recognize common headache types and to initiate therapy for tension-type headaches and migraines. Patients with complicated headache scenarios should be referred to a neurologist for consultation.

Imaging
Migraine headaches
Treatment
Trigeminal autonomic cephalalgias
Triptans


Fatal outcome of SARS-CoV-2 infection (B1.1.7) in a 4-year-old child.

Abstract: This case report highlights details of a case of critical acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) with B1.1.7 variant in a 4-year-old girl who died due to pneumonia and pulmonary hemorrhage. The girl was referred to our University ECMO Center from another University hospital for veno-arterial extracorporeal membrane oxygenation (VA-ECMO). In the clinical course, superinfection with Pseudomonas aeruginosa was detected. Virological evidence of herpes simplex sepsis was also obtained in blood samples on her day of death. Transcription polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection in lung tissue. Postmortem computed tomography showed pulmonary hemorrhage with inhomogeneous density values in both lungs. Lung tissue showed no ventilated areas. Autopsy revealed a massively congested lung with evidence of acute respiratory distress syndrome (ARDS) and pneumonia with multiple abscesses. Histopathology showed a mixture of diffuse alveolar injury with hyaline membranes, massive hemorrhage, and bronchopneumonia with multiple granulocytic abscesses. Cardiac examination revealed pericarditis. Suspicion of myocarditis or myocardial infarction could not be confirmed microscopically. To our knowledge, this is the first autopsy-based case report of the death of a previously healthy child due to the new variant B 1.1.7 in Germany.

Menger|Johanna|J| Apostolidou|Sofia|S| Edler|Carolin|C| Kniep|Inga|I| Kobbe|Robin|R| Singer|Dominique|D| Sperhake|Jan-Peter|JP|

SARS-CoV-2 B1.1.7 Autopsy COVID Children MIS-C


Functional assessment of encapsulated citral for controlling necrotic enteritis in broiler chickens.

Abstract: Development of viable alternatives to antibiotics to control necrotic enteritis (NE) caused by Clostridium perfringensis becoming urgent for chicken production due to pessures on poultry producers to limit or stop the use of antibiotics in feed. We have previously identified citral as a potential alternative to antibiotics. Citral has strong antimicrobial activity and can be encasupsulated in a powder form for protection from loss during feed processing, storage, and intestinal delivery. In the present study, encapsulated citral was evaluated both in vitro and in vivo for its antimicrobial activity against C. perfringens Encapsulation did not adversely affect the antimicrobial activity of citral. In addition, encapsulated citral was superior to the unencapsulated form in retaining its antimicrobial activity after treatment with simulated gastrointestinal fluids and in the presence of chicken intestinal digesta. In addition, the higher antimicrobial activity of encapsulated citral was confirmed in digesta samples from broilers that had been gavaged with encapsulated or unencapsulated citral. In broilers infected with C. perfringens, the diets supplemented with encapsualted citral at both 250 and 650 μg/g significantly reduced intestinal NE lesions, which was comparable to the effect of bacitracin- and salinomycin-containing diets. However, supplementation with the encapsulated citral appeared to have no significant impact on the intestinal burden of Lactobacillus These data indicate that citral can be used to control NE in chickens after proper protection by encapsulation.

Yang|Yuexi|Y|
Wang|Qi|Q|
Diarra|Moussa S|MS|
Yu|Hai|H|
Hua|Yufei|Y|
Gong|Joshua|J|

encapsulation
citral
necrotic enteritis
broiler
Clostridium perfringen


Fossils matter: improved estimates of divergence times in Pinus reveal older diversification.

Abstract:
BACKGROUND
The taxonomy of pines (genus Pinus) is widely accepted and a robust gene tree based on entire plastome sequences exists. However, there is a large discrepancy in estimated divergence times of major pine clades among existing studies, mainly due to differences in fossil placement and dating methods used. We currently lack a dated molecular phylogeny that makes use of the rich pine fossil record, and this study is the first to estimate the divergence dates of pines based on a large number of fossils (21) evenly distributed across all major clades, in combination with applying both node and tip dating methods.

RESULTS
We present a range of molecular phylogenetic trees of Pinus generated within a Bayesian framework. We find the origin of crown Pinus is likely up to 30 Myr older (Early Cretaceous) than inferred in most previous studies (Late Cretaceous) and propose generally older divergence times for major clades within Pinus than previously thought. Our age estimates vary significantly between the different dating approaches, but the results generally agree on older divergence times. We present a revised list of 21 fossils that are suitable to use in dating or comparative analyses of pines.

CONCLUSIONS
Reliable estimates of divergence times in pines are essential if we are to link diversification processes and functional adaptation of this genus to geological events or to changing climates. In addition to older divergence times in Pinus, our results also indicate that node age estimates in pines depend on dating approaches and the specific fossil sets used, reflecting inherent differences in various dating approaches. The sets of dated phylogenetic trees of pines presented here provide a way to account for uncertainties in age estimations when applying comparative phylogenetic methods.

Saladin|Bianca|B|0000-0002-4544-6562
Leslie|Andrew B|AB|
Wüest|Rafael O|RO|
Litsios|Glenn|G|
Conti|Elena|E|
Salamin|Nicolas|N|
Zimmermann|Niklaus E|NE|

Pines
Phylogeny
Bayesian clock dating
Fossil calibration
Fossilized birth-death
Molecular clock calibration
Node dating


Evaluation of the Sensitivity of the Flow Through Assay for detection of White Spot Syndrome Virus (WSSV) using a cocktail of monoclonal antibodies.

Abstract: A panel of four monoclonal antibodies (C-05, C-14, C-38 and C-56) specific to VP28 of White spot syndrome virus (WSSV) were evaluated individually and in cocktail to increase sensitivity of the Flow Through Assay (FTA) for detection of the virus. Recombinant VP28 and semi purified WSSV was used as antigen for evaluation. Out of the total 11 cocktails and four individual of MAbs, 2 MAb cocktails C-05 + C-56 and C-14 + C-56 exhibited highest sensitivity in the FTA. The two MAb cocktail were 100 times more sensitive than 1-step PCR and nearly equivalent to 2-step PCR for the detection of WSSV. The detection limit of WSSV by MAb cocktail increased by two fold compared to the single MAb C-05 currently being used in (FTA).

Inchara|U B|UB|
Sathish|R P|RP|
Shankar|K M|KM|
Abhiman|P B|PB|
Prakash|P|P|

D000911:Antibodies, Monoclonal
D016133:Polymerase Chain Reaction
D046848:White spot syndrome virus 1

WSSV
Cocktail
Monoclonal antibodies
FTA
Immunodetection


Pharmacological cyclin dependent kinase inhibitors: Implications for colorectal cancer.

Abstract: Colorectal cancer accounts for a significant proportion of cancer deaths worldwide. The need to develop more chemotherapeutic agents to combat this disease is critical. Cyclin dependent kinases (CDKs), along with its binding partner cyclins, serve to control the growth of cells through the cell cycle. A new class of drugs, termed CDK inhibitors, has been studied in preclinical and now clinical trials. These inhibitors are believed to act as an anti-cancer drug by blocking CDKs to block the uncontrolled cellular proliferation that is hallmark of cancers like colorectal cancer. CDK article provides overview of the emerging drug class of CDK inhibitors and provides a list of ones that are currently in clinical trials.

Balakrishnan|Archana|A| Vyas|Arpita|A| Deshpande|Kaivalya|K| Vyas|Dinesh|D|

D000818:Animals
D000970:Antineoplastic Agents
D049109:Cell Proliferation
D015179:Colorectal Neoplasms
D018844:Cyclin-Dependent Kinases
D006801:Humans
D058990:Molecular Targeted Therapy
D047428:Protein Kinase Inhibitors
D015398:Signal Transduction
D016896:Treatment Outcome

Cyclin
Cyclin dependent kinase inhibitor
Colorectal cancer


Microanatomical Record of Cortical Bone Remodeling and High Vascularity in a Fossil Giant Rat Midshaft Femur.

Abstract: Rat cortical bone does not typically undergo secondary (Haversian) remodeling. Haversian organization of rat bone has been mainly observed in experimental settings following biomechanical or dietary manipulation. Here, we report an observation of cortical secondary osteons within a histological femur cross-section from an extinct (late Quaternary) form of Timorese giant rat (Murinae gen. et sp. indet). The medio-lateral midshaft diameter of its femur, used as a measure of bone size, is 6.15 mm and indicates a heavier than normal skeletal frame. We compare this sample to bone histology in a small rat's midshaft femur of 2.33 mm diameter. A complete lack of Haversian bone remodeling characteristics is noted for the smaller sample, which is dominated by radial vascular canals. The giant rat shows clear secondary osteons and diffuse vascularity mainly composed of tightly packed longitudinal canals across its cortex. It appears that rat cortical bone can undergo bone remodeling, and is organized in a highly vascularized manner, in insular giant cases. Our findings from Timor align with results reported in experimental rat model skeletal biology literature and other insular fossil rat material. Where macroanatomical examination is limited, histological observations on fossil rat limb bones have the potential to aid reconstructions of life history and skeletal growth aspects in these rodents. Anat Rec, 302:1934-1940, 2019. © 2019 American Association for Anatomy.

bone remodeling
femur
secondary osteon
Murinae
bone histology
Haversian canal


Affective recovery from stress and its associations with sleep.

Abstract: Good sleep habits are important for emotional well-being. Studies have linked sleep with people's ability to regulate their emotions in response to stressful events, yet little is known specifically about how sleep is related to a person's ability to recover affectively from a stressful experience. The current study examined self-reported sleep habits and their associations with both positive and negative affective recovery from a laboratory-induced stressor. Participants (N = 120) reported their sleep habits over the previous month and then engaged in a laboratory psychosocial stress task. Affect was measured before, during, and 6 minutes after the task. Different aspects of sleep were related to poorer positive and negative affective recovery. Worse sleep quality was associated with higher post-recovery negative affect, whereas worse sleep efficiency was associated with lower post-recovery positive affect. Findings suggest that poor sleep is associated with prolonged affective recovery from a stressful event. Implications for health and well-being are discussed.

D007319:Sleep Initiation and Maintenance Disorders

affective recovery
stress
sleep
negative affect
positive affect


The effectiveness of axillary reverse mapping in preventing breast cancer-related lymphedema: a meta-analysis based on randomized controlled trials.

Abstract:
Background
Here, we carried out an extensive meta-analysis to investigate the effectiveness of the use of axillary reverse mapping (ARM) during axillary lymph node dissection (ALND) in preventing breast cancer-related lymphedema (BCRL).

Methods
Database searches to identify relevant randomized controlled trials (RCTs) were performed of MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library. Eligible articles with a publication date from database establishment to December 2020 were retrieved by combining keywords including: "breast cancer", "breast carcinoma", "breast neoplasm", "axillary reverse mapping", "axillary lymph node dissection", "lymphatic arm drainage", and "lymphedema". Independent data extraction was conducted, and Review Manager (version 5.3) was used for statistical analyses.

Results
Five eligible RCTs were included in the meta-analysis. A total of 37 patients suffered arm lymphedema (37/786, 4.71%) in the experimental group (ARM during ALND), compared with 164 arm lymphedemas (164/873, 18.79%) in the control group (ALND alone). The results showed that ARM during ALND was superior to ALND alone in reducing the incidence of BCRL [OR =0.20, 95% confidence intervals (CI): 0.13-0.29, P<0.00001]; however, the 2 procedures did not differ significantly in terms of oncological safety or shoulder movement (OR =0.30, 95% CI: 0.03-2.96, P=0.30; OR =0.44, 95% CI: 0.14-1.40, P=0.17).

Conclusions
ARM during ALND can prevent and reduce the occurrence of BCRL in patients with early-stage BC during long-term follow-up. Due to the limited number of RCTs available, more in-depth, high-quality RCTs are urgently needed to provide a reliable and convincing basis for the application of ARM during ALND.

Guo|Xuhui|X| Jiao|Dechuang|D| Zhu|Jiujun|J| Xiao|Hui|H| Zhao|Xin|X| Yang|Yue|Y| Zhao|Yajie|Y| Liu|Zhenzhen|Z|

lymphedema
meta-analysis
Axillary reverse mapping (ARM)
axillary lymph node dissection (ALND)
breast cancer (BC)


Facile fabrication of novel konjac glucomannan films with antibacterial properties via microfluidic spinning strategy.

Abstract: The exploration of methods to produce biomaterials with antibacterial properties in ultra-small scales is of great scientific and technological interest. Here, we reported a microfluidic spinning approach to prepare a novel film combined with konjac glucomannan (KGM), polyvinylpyrrolidone (PVP), and epigallocatechin gallate (EGCG). The film was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. This film was transparent, orderly, thermally stable, and uniform in size, with an average width less than 1 μm. Also, the film exhibited excellent antibacterial efficiency (97.1% against E. coli, 99.7% against S. aureus, 97.3% against S. enterica and 99.9% against B. subtilis) in our antibacterial test. In addition, the film promoted wound healing with the advanced development of neovascularization and hair follicles. This strategy provides a facile and green pathway for the construction of biomaterial films for medical applications.

Ni|Yongsheng|Y| Lin|Wanmei|W| Mu|Ruojun|R| Wu|Chunhua|C| Lin|Zheya|Z| Chen|Su|S| Pang|Jie|J|

D017550:Spectroscopy, Fourier Transform Infrared

Konjac glucomannan
Films
Antibacterial properties
Wound healing
Microfluidic spinning technology


Nanotoxicologic Effects of PLGA Nanoparticles Formulated with a Cell-Penetrating Peptide: Searching for a Safe pDNA Delivery System for the Lungs.

Abstract: The use of cell-penetrating peptides (CPPs) in combination with nanoparticles (NPs) shows great potential for intracellular delivery of DNA. Currently, its application is limited due to the potential toxicity and unknown long-term side effects. In this study NPs prepared using a biodegradable polymer, poly(lactic⁻co⁻glycolic acid (PLGA) in association with a CPP, was assessed on two lung epithelial cell lines (adenocarcinomic human alveolar basal epithelial cells (A549) and normal bronchial epithelial cells (Beas-2B cells)). Addition of CPP was essential for intracellular internalization. No effects were observed on the mitochondrial activity and membrane integrity. Cells exposed to the NPs⁻DNA⁻CPP showed low inflammatory response, low levels of apoptosis and no activation of caspase-3. Increase in necrotic cells (between 10%⁻15%) after 24 h of incubation and increase in autophagy, induced by NPs⁻DNA⁻CPP, are likely to be related to the lysosomal escape mechanism. Although oxidative stress is one of the main toxic mechanisms of NPs, NPs⁻DNA⁻CPP showed decreased reactive oxygen species (ROS) production on Beas-2B cells, with potential antioxidant effect of CPP and no effect on A549 cells. This NP system appears to be safe for intracellular delivery of plasmid DNA to the lung epithelial cells. Further investigations should be conducted in other lung-related systems to better understand its potential effects on the lungs.

Gomes Dos Reis|Larissa|L|
Lee|Wing-Hin|WH|
Svolos|Maree|M|
Moir|Lyn Margaret|LM|
Jaber|Rima|R|
Windhab|Norbert|N|
Young|Paul Michael|PM|
Traini|Daniela|D|0000-0002-7173-017X

alveolar
bronchial
apoptosis
autophagy
gene delivery


Effectiveness of a village-based intervention for depression in community-dwelling older adults: a randomised feasibility study.

Abstract:
BACKGROUND
Although a focus on late-life depression may help preventing suicide in older adults, many older people, especially those living in rural areas, have relatively low accessibility to treatment. This study examined the feasibility and effectiveness of a village-based intervention for depression targeting older adults living in rural areas.

METHODS
A community-based randomised pilot trial was performed in two small rural villages in South Korea. Two villages were randomly selected and assigned to the intervention or active control group; all older adults living in the two villages (n = 451) were included in the intervention program or received standard Community Mental Health Service (CMHS) care, and the effectiveness of the program was examined using representative samples from both groups (n = 160). The 12-week intervention included case management according to individual risk level and group-based activities. Healthy residents living in the intervention village who played major roles in monitoring at-risk older individuals were supervised by CMHS staff. The score on the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) was the primary outcome, while social network, functional status, and global cognitive function were secondary outcomes. Linear mixed models including the factors of intervention group, time, and their interaction were used to examine group differences in changes in primary and secondary outcomes from baseline to follow up.

RESULTS
Overall, there was no significant group × time interaction with respect to the SGDS-K score, but older individuals with more depressive symptoms at baseline (SGDS-K ≥ 6) tended to have a lower likelihood of progressing to severe depression at post-intervention. The social network was strengthened in the intervention group, and there was a significant group × time interaction (F[df1, df2], 5.29 [1, 153], p = 0.023).

CONCLUSION
This study examined a 12-week village-based intervention for late-life depression in which the CMHS helped village-dwellers deal with late-life depression in their communities. Although the intervention improved social interactions among older adults, it did not reduce depressive symptoms. Further studies including more rural villages and long-term follow up are needed to confirm the effectiveness of this prevention program.

TRIAL REGISTRATION
NCT04013165 (date: 9 July 2019, retrospectively registered).

Oh|In Mok|IM|
Cho|Maeng Je|MJ|
Hahm|Bong-Jin|BJ|
Kim|Byung-Soo|BS|
Sohn|Jee Hoon|JH|
Suk|Hye Won|HW|
Jung|Bu Young|BY|
Kim|Hye Jung|HJ|
Kim|Hyeon A|HA|
Choi|Ki Bok|KB|
You|Da Hye|DH|
Lim|Ah Reum|AR|
Park|In Ok|IO|
Ahn|Jeung Hyuck|JH|
Lee|Hee|H|
Kim|Yeon Hee|YH|
Kim|Mi Ra|MR|
Park|Jee Eun|JE|0000-0001-6097-3275

Intervention
Late-life depression
Suicide
Community-based
Old-aged


The role of the NADPH oxidase derived brain oxidative stress in the cocaine-related death associated with excited delirium: A literature review.

Abstract: Excited delirium syndrome (ExDS) is a term used to describe a clinical condition characterized by bizarre and aggressive behaviour, commonly associated with the use of psychoactive compounds, especially cocaine. The pathophysiology of ExDS is complex and not yet fully understood. In addition to a central dopamine hypothesis, other mechanisms are thought to be involved in cocaine-related ExDS, such as increased reactive oxygen species production by the family of the NADPH oxidase NOX enzymes. In this review, we will summarize current knowledge on the crucial contribution of brain NADPH oxidase derived oxidative stress in the development of cocaine-induced ExDS. Data from animal models as well as human evidence will be discussed.

Schiavone|Stefania|S| Neri|Margherita|M| Mhillaj|Emanuela|E| Pomara|Cristoforo|C| Trabace|Luigia|L| Turillazzi|Emanuela|E|

NADPH oxidase
Brain
Oxidative stress
Excited delirium
Cocaine


Trichoderma inoculation augments grain amino acids and mineral nutrients by modulating arsenic speciation and accumulation in chickpea (Cicer arietinum L.).

Abstract: Trichoderma reesei is an industrially important fungi which also imparts stress tolerance and plant growth promotion in various crops. Arsenic (As) contamination of field soils is one of the challenging problems in agriculture, posing potential threats for both human health and the environment. Plants in association with microbes are a liable method to improve metal tolerance and enhance crop productivity. Chickpea (Cicer arietinum L.), is an important grain legume providing cheap source of protein in semi-arid regions including As affected areas. In this study we report the role of T. reesei NBRI 0716 (NBRI 0716) in supporting chickpea growth and improving soil quality in As simulated conditions. NBRI 0716 modulated the As speciation and its availability to improve grain yield and quality (amino acids and mineral content) in chickpea (C. arietinum L.) plants grown in As spiked soil (100 mg As kg(-1) soil). Arsenic accumulation and speciation results indicate that arsenate [As(V)] was the dominant species in chickpea seeds and rhizosphere soil. The Trichoderma reduced total grain inorganic As (Asi) by 66% and enhanced dimethylarsonic acid (DMA) and monomethylarsinic acid (MMA) content of seed and rhizosphere soil. The results indicate a probable role of NBRI 0716 in As methylation as the possible mechanism for maneuvering As stress in chickpea. Analysis of functional diversity using carbon source utilization (Biolog) showed significant difference in diversity and evenness indices among the soil microbial rhizosphere communities. Microbial diversity loss caused by As were prevented in the presence of Trichoderma NBRI 0716.

Tripathi|Pratibha|P|
Singh|Poonam C|PC|
Mishra|Aradhana|A|
Tripathi|Rudra D|RD|
Nautiyal|Chandra S|CS|

Trichoderma
Amino acid
Arsenic
Chickpea
Mineral element accumulation


CT-guided percutaneous aspiration of Tarlov cyst: a case report of 2-year follow up.

Abstract: Tarlov cysts are a rare pathology characterized by sac formations at the nerve root in the sacrum. Although many options have been proposed, there is still no consensus regarding the optimal treatment strategy. The authors report a case involving a 43-year woman with a sacral perineural cyst causing buttock pain and anus discomfort for 4 years. The patient successfully underwent computed tomography (CT)-guided aspiration. She currently has no symptoms, and 2-year follow-up magnetic resonance imaging revealed a decrease in cyst size. CT-guided aspiration is a safe and effective treatment option, and leads to improvement in cyst-related symptoms with minimal risk.

Sahin|Ertugrul|E|
Lee|Sang-Ho|SH|
Eun|Sang Soo|SS|

Tarlov cyst
case report
perineural cyst
CT guided aspiration
magnetic resonance imaging (MRI)


Estimating uncertainty in predicted folding free energy changes of RNA secondary structures.

Abstract: Nearest neighbor parameters for estimating the folding stability of RNA are commonly used in secondary structure prediction, for generating folding ensembles of structures, and for analyzing RNA function. Previously, we demonstrated that we could quantify the uncertainties in each nearest neighbor parameter by perturbing the underlying optical melting data within experimental error and rederiving the parameters, which accounts for the substantial correlations that exist between the parameters. In this contribution, we describe a method to estimate uncertainty in the estimated folding stabilities of RNA structures, accounting for correlations in the nearest neighbor parameters. This method is incorporated in the RNA structure software package.

Gibbs free energy change
nearest neighbor rules


Habitual consumption of long-chain n-3 PUFAs and fish attenuates genetically associated long-term weight gain.

Abstract:
BACKGROUND
A growing amount of data suggests that n-3 (ω-3) polyunsaturated fatty acid (PUFA) intake may modify the genetic association with weight change.

OBJECTIVES
We aimed to prospectively test interactions of habitual consumption of n-3 PUFAs or fish, the major food source, with overall genetic susceptibility on long-term weight change.

DESIGN
Gene-diet interactions were examined in 11,330 women from the Nurses' Health Study (NHS), 6773 men from the Health Professionals Follow-Up Study (HPFS), and 6254 women from the Women's Health Initiative (WHI).

RESULTS
In the NHS and HPFS cohorts, food-sourced long-chain n-3 PUFA intake showed directionally consistent interactions with genetic risk score on long-term changes in BMI (P-interaction = 0.01 in the HPFS, 0.15 in the NHS, and 0.01 in both cohorts combined). Such interactions were successfully replicated in the WHI, an independent cohort (P-interaction = 0.02 in the WHI and 0.01 in the combined 3 cohorts). The genetic associations with changes in BMI (in kg/m2) consistently decreased (0.15, 0.10, 0.07, and -0.14 per 10 BMI-increasing alleles) across the quartiles of long-chain n-3 PUFAs in the combined cohorts. In addition, high fish intake also attenuated the genetic associations with long-term changes in BMI in the HPFS (P-interaction = 0.01), NHS (P-interaction = 0.03), WHI (P-interaction = 0.10), and the combined cohorts (P-interaction = 0.01); and the differences in BMI changes per 10 BMI-increasing alleles were 0.16, 0.06, -0.08, and -0.18, respectively, across the categories (≤1, 1∼4, 4∼6, and ≥7 servings/wk) of total fish intake. Similar interactions on body weight were observed for fish intake (P-interaction = 0.003) and long-chain n-3 PUFA intake (P-interaction = 0.12).

CONCLUSION
Our study provides replicable evidence to show that high intakes of fish and long-chain n-3 PUFAs are associated with an attenuation of the genetic association with long-term weight gain based on results from 3 prospective cohorts of Caucasians.

Huang|Tao|T|
Wang|Tiange|T|
Heianza|Yoriko|Y|
Zheng|Yan|Y|
Sun|Dianjianyi|D|
Kang|Jae H|JH|
Pasquale|Louis R|LR|
Rimm|Eric B|EB|
Manson|JoAnn E|JE|
Hu|Frank B|FB|
Qi|Lu|L|

D020022:Genetic Predisposition to Disease

fish
genetic association
weight gain
gene–diet interaction
n–3 polyunsaturated fatty acids


Quantifying spatial heterogeneity of chlorophyll fluorescence during plant growth and in response to water stress.

Abstract:
BACKGROUND
Effects of abiotic and biotic stresses on plant photosynthetic performance lead to fitness and yield decrease. The maximum quantum efficiency of photosystem II (F v/F m) is a parameter of chlorophyll fluorescence (ChlF) classically used to track changes in photosynthetic performance. Despite recent technical and methodological advances in ChlF imaging, the spatio-temporal heterogeneity of F v/F m still awaits for standardized and accurate quantification.

RESULTS
We developed a method to quantify the dynamics of spatial heterogeneity of photosynthetic efficiency through the distribution-based analysis of F v/F m values. The method was applied to Arabidopsis thaliana grown under well-watered and severe water deficit (survival rate of 40%). First, whole-plant F v/F m shifted from unimodal to bimodal distributions during plant development despite a constant mean F v/F m under well-watered conditions. The establishment of a bimodal distribution of F v/F m reflects the occurrence of two types of leaf regions with contrasted photosynthetic efficiency. The distance between the two modes (called S) quantified the whole-plant photosynthetic heterogeneity. The weighted contribution of the most efficient/healthiest leaf regions to whole-plant performance (called W max) quantified the spatial efficiency of a photosynthetically heterogeneous plant. Plant survival to water deficit was associated to high S values, as well as with strong and fast recovery of W max following soil rewatering. Hence, during stress surviving plants had higher, but more efficient photosynthetic heterogeneity compared to perishing plants. Importantly, S allowed the discrimination between surviving and perishing plants four days earlier than the mean F v/F m. A sensitivity analysis from simulated dynamics of F v/F m showed that parameters indicative of plant tolerance and/or stress intensity caused identifiable changes in S and W max. Finally, an independent comparison of six Arabidopsis accessions grown under well-watered conditions indicated that S and W max are related to the genetic variability of growth.

CONCLUSIONS
The distribution-based analysis of ChlF provides an efficient tool for quantifying photosynthetic heterogeneity and performance. S and W max are good indicators to estimate plant survival under water stress. Our results suggest that the dynamics of photosynthetic heterogeneity are key components of plant growth and tolerance to stress.

Bresson|Justine|J| Vasseur|François|F| Dauzat|Myriam|M| Koch|Garance|G| Granier|Christine|C| Vile|Denis|D|

Plant growth
Photosynthetic performance
Arabidopsis thaliana
Plant survival
Sensitivity analysis
Chlorophyll fluorescence imaging
Heterogeneity of Fv/Fm values
Modelling
Pixels distribution


Quantification of white matter cellularity and damage in preclinical and early symptomatic Alzheimer's disease.

Abstract: Interest in understanding the roles of white matter (WM) inflammation and damage in the pathophysiology of Alzheimer disease (AD) has been growing significantly in recent years. However, in vivo magnetic resonance imaging (MRI) techniques for imaging inflammation are still lacking. An advanced diffusion-based MRI method, neuro-inflammation imaging (NII), has been developed to clinically image and quantify WM inflammation and damage in AD. Here, we employed NII measures in conjunction with cerebrospinal fluid (CSF) biomarker classification (for β-amyloid (Aβ) and neurodegeneration) to evaluate 200 participants in an ongoing study of memory and aging. Elevated NII-derived cellular diffusivity was observed in both preclinical and early symptomatic phases of AD, while disruption of WM integrity, as detected by decreased fractional anisotropy (FA) and increased radial diffusivity (RD), was only observed in the symptomatic phase of AD. This may suggest that WM inflammation occurs earlier than WM damage following abnormal Aβ accumulation in AD. The negative correlation between NII-derived cellular diffusivity and CSF Aβ42 level (a marker of amyloidosis) may indicate that WM inflammation is associated with increasing Aβ burden. NII-derived FA also negatively correlated with CSF t-tau level (a marker of neurodegeneration), suggesting that disruption of WM integrity is associated with increasing neurodegeneration. Our findings demonstrated the capability of NII to simultaneously image and quantify WM cellularity changes and damage in preclinical and early symptomatic AD. NII may serve as a clinically feasible imaging tool to study the individual and composite roles of WM inflammation and damage in AD.

Wang|Qing|Q|
Wang|Yong|Y|
Liu|Jingxia|J|
Sutphen|Courtney L|CL|
Cruchaga|Carlos|C|
Blazey|Tyler|T|
Gordon|Brian A|BA|
Su|Yi|Y|
Chen|Charlie|C|
Shimony|Joshua S|JS|
Ances|Beau M|BM|
Cairns|Nigel J|NJ|
Fagan|Anne M|AM|
Morris|John C|JC|
Benzinger|Tammie L S|TLS|

D038524:Diffusion Magnetic Resonance Imaging

Inflammation
Magnetic resonance imaging
Neuro-inflammation imaging
Cerebrospinal fluid
Diffusion basis spectrum imaging
Early symptomatic Alzheimer disease
Preclinical Alzheimer disease
White matter damage


Porphyrin-Loaded TyroSpheres for the Intracellular Delivery of Drugs and Photoinduced Oxidant Species.

Abstract: In order to understand the intracellular delivery of drugs and to improve the cell killing efficiency of photosensitizers (PSs) used in photodynamic therapy (PDT), we prepared TyroSphere nanoparticles, which are triblock polymer [poly(ethylene glycol)-block-oligo(desaminotyrosyltyrosine octyl ester suberate)-block-poly(ethylene glycol)] aggregates, loaded with amphiphilic porphyrins with either positive (CisDiMPyP) or negative (TPPS2a) charges. Their physicochemical and photochemical properties were investigated, as well as the efficiency and mechanism of PDT death in a cervical cancer cell line (HeLa). The photophysical properties of both PSs were improved when loaded in the nanocarrier, with a decrease in aggregation as well as an increase in the yield of singlet oxygen generation. The physical and chemical stability of TyroSphere nanoparticles allows them to enter cells and to promote the slow intracellular delivery of part of the PSs. Confocal steady-state and lifetime-resolved fluorescence imaging microscopy data showed that the released PSs are free to target their natural intracellular targets, which are mitochondria and lysosomes for CisDiMPyP and TPPS2a, respectively. The photodynamic efficiency of cell killing was increased considerably compared with the free PSs (∼3×), but the mechanism of cell death was the same as that of the free PSs, which are acute necro-apoptosis for CisDiMPyP and autophagy malfunction for TPPS2a, reflecting the specific damage in mitochondria and lysosomes, respectively. We are confident that TyroSpheres provide a novel and efficient platform to administrate PDT photosensitizers, as well as other drugs with intracellular targets.

photosensitizer
photodynamic therapy
drug delivery
nanospheres


Diagnosis of more gestational diabetes lead to better pregnancy outcomes: Comparing the International Association of the Diabetes and Pregnancy Study Group criteria, and the Carpenter and Coustan criteria.

Abstract:
AIMS/INTRODUCTION
The International Association of the Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes are associated with increased prevalence. However, it remains unknown if intervention for more women with gestational diabetes mellitus by the IADPSG criteria results in better pregnancy outcomes than adopting the Carpenter and Coustan (C&C) criteria in Asian populations.

MATERIALS AND METHODS
This was a retrospective cohort study. A total of 1,840 women, 952 subjects by the IADPSG criteria and 888 subjects by the C&C criteria, who delivered singletons in 2011 in a single tertiary center, were included in the study. The same therapeutic interventions were offered to women with gestational diabetes mellitus by the two criteria. Maternal and neonatal outcomes were evaluated.

RESULTS
Adopting the IADPSG criteria increased the prevalence of gestational diabetes mellitus diagnosis to 13.44%, compared with 2.59% by the C&C criteria. The diagnosis was made 3 weeks earlier by the IADPSG criteria (27 vs 30.5 weeks, P < 0.0001). Adopting the IADPSG criteria was associated with reduced risk of primary cesarean section (adjusted odds ratio 0.79, 95% confidence interval 0.63-0.998, P < 0.05) and having any one of the adverse fetal outcomes (adjusted odds ratio 0.79, 95% confidence interval 0.64-0.998, P < 0.05), including birthweight >90th percentile, jaundice, admission to neonatal intensive care unit, birth trauma, neonatal hypoglycemia and fetal death.

CONCLUSIONS
Adopting the IADPSG criteria is associated with improved pregnancy outcomes, at the expense of increased prevalence of gestational diabetes mellitus diagnosis.

Wu|En-Tzu|ET| Nien|Feng-Jung|FJ| Kuo|Chun-Heng|CH| Chen|Szu-Chi|SC| Chen|Kuan-Yu|KY| Chuang|Lee-Ming|LM| Li|Hung-Yuan|HY| Lee|Chien-Nan|CN|


Physiology of cold-stored platelets.

Abstract: Platelet transfusions are a life-saving medical intervention used for the treatment of thrombocytopenia or hemorrhage. Extensive research has gone into trying to understand how to store platelets prior to the transfusion event. Much has been learned about storage bag materials, synthetic solutions, and how temperature impacts platelet viability and function. While room temperature storage of platelets preserves 24-hour in vivo platelet recovery and survival there is a greater risk for bacterial growth. Therefore, cold storage of platelets has become attractive due to the reduction in potential bacterial proliferation and the maintenance of platelet function beyond 5 days of storage. Cold stored platelets, however, have their own set of challenges. Cold stored platelets become activated through several mechanisms. The morphological and molecular changes that occur due to cold exposure enhance their ability to participate in the hemostatic process at the cost of rapid clearance from circulation. This review focuses on the underlying mechanisms leading to cold platelet activation and the receptor modifications involved in platelet clearance.

Clearance
Cold platelets
Platelet activation


Radiation-Induced Rib Fractures on Magnetic Resonance Imaging Following Proton Therapy for Breast Cancer With Pencil Beam Scanning.

Abstract: Radiation-induced rib fractures (RIRF) are long-term complications associated with irradiation of the chest/chest wall. RIRFs are commonly seen in lung- or breast-cancer patients treated with stereotactic body radiotherapy (SBRT) or conventional external beam radiation therapy (EBRT), respectively. We report a case of a 31-year-old female presenting with pathological fractures of the third, fourth, and fifth ribs discovered on magnetic resonance imaging (MRI) as a complication from pencil beam scanning (PBS) proton therapy (PT), of the whole left breast and regional lymph nodes. To our knowledge, this presentation is the first to be initially reported on MRI in radiological literature.

Way|Ashley R|AR|
Wasserman|Paul L|PL|
Mailhot|Raymond|R|
Letter|Haley|H|

proton therapy
pencil beam scanning
high risk breast cancer
locally advanced breast-cancer
pathological rib fracture
radiation induced rib fracture
radiation induced skeletal injury


LYSOPHOSPHATIDIC ACID ACYLTRANSFERASES 4 and 5 are involved in glycerolipid metabolism and nitrogen starvation response in Arabidopsis.

Abstract: Nitrogen (N) deficiency triggers an accumulation of a storage lipid triacylglycerol (TAG) in seed plants and algae. Whereas the metabolic pathway and regulatory mechanism to synthesize TAG from diacylglycerol are well known, enzymes involved in the supply of diacylglycerol remain elusive under N starvation. Lysophosphatidic acid acyltransferase (LPAT) catalyzes an important step of the de novo phospholipid biosynthesis pathway and thus has a strong flux control in the biosynthesis of phospholipids and TAG. Five LPAT isoforms are known in Arabidopsis; however, the functions of LPAT4 and LPAT5 remain elusive. Here, we show that LPAT4 and LPAT5 are functional endoplasmic-reticulum-localized LPATs. Seedlings of the double knockout mutant lpat4-1 lpat5-1 showed reduced content of phospholipids and TAG under normal growth condition. Under N starvation, lpat4-1 lpat5-1 seedlings showed severer growth defect than the wild-type in shoot. The phenotype was similar to dgat1-4, which affects a major TAG biosynthesis pathway and showed similarly reduced TAG content as the lpat4-1 lpat5-1. We suggest that LPAT4 and LPAT5 may redundantly function in endoplasmic-reticulum-localized de novo glycerolipid biosynthesis for phospholipids and TAG, which is important for the N starvation response in Arabidopsis.

D018506:Gene Expression Regulation, Plant

lysophosphatidic acid acyltransferase
nitrogen starvation
triacylglycerol
phospholipid biosynthesis
Arabidopsis thaliana


Analysis of four governance factors on efforts of water governing agencies to increase water reuse in the San Antonio Region.

Abstract: Securing sources for water reuse and coordinating efforts of water governing agencies to do so are critical to realizing the potential of reused water to provide nearly 24% of the water demand of the San Antonio Region, defined as regions "L" and "K" by the Texas Water Development Board (TWDB). This research identifies key governance factors that contribute to increasing water reuse within the water planning sector and tests four governance-related hypotheses for their impact on efforts to increase water reuse in the Region. Variables tested include: the type and scale of water governance agency, the agency's frequency of communication with the TWDB, and the agency's familiarity with the TWDB water strategy supplies as defined in the Texas State Water Plan of 2017. A questionnaire addressing these variables was sent to water governing agencies in regions L and K; the response rate was 39.5%. Each variable was cross-tabulated with agency efforts to increase water reuse. Seven regression analysis models were calculated among the factors to test for statistical significance and impact on increasing water reuse efforts. Results indicate that nearly 70% of agencies in the regions have efforts to increase water reuse by as much as 10%. Among the tested hypotheses, frequency in communication with the TWDB was statistically significant for increasing agency efforts to reuse water. Results from these hypotheses are expected to help water managers identify key, governance-related factors that contribute to increased water reuse.

Governance
Water reuse
Water planning
Water management


Shift of nitrate sources in groundwater due to intensive livestock farming on Jeju Island, South Korea: With emphasis on legacy effects on water management.

Abstract: Time lags between anthropogenic nitrogen inputs and their impacts to nitrate levels cause a misunderstanding for sources and subsequently misguide the groundwater management.We investigated the hydrochemical data of groundwater samples (n = 172 from 49 wells) with chlorofluorocarbons (CFCs)-based groundwater age dating and stable N (δ15N) and O isotopes (δ18O) of nitrate to assess the legacy effect of livestock farming to groundwater in an agricultural area where intensive livestock farming started in the 1970s and illegal dumping of manure wastewater in a lava cave was revealed in 2015. Approximately 90% of the groundwater samples had nitrate concentrations exceeding the natural threshold (5.5 mg/L NO3-) for nitrate contamination and 34% exceeded the World Health Organization's guideline for drinking water quality (44.3 mg/L), indicating severe nitrate contamination. The δ15NNO3 values (5.5 to 24.3‰) in groundwater exceeding the threshold of nitrate showed that livestock manure was a major nitrate source, while ammonium fertilizer also seemed influential given the δ15NNO3 values in the overlapping fields of N sources. Factor analysis of hydrochemical data also supported nitrate contamination by manure as well as by plant farming in the study area. Based on the spatial distribution of nitrate levels and δ15NNO3, livestock farming affected nitrate contamination by illegal manure dumping in the leakage cave. According to a Bayesian mixing model, the contribution of manure wastewater was 33.5 to 81.8% as of 2015-2018, with the rest from fertilizers. Meanwhile, the groundwater ages showed negative correlations with both nitrate levels (r = -0.90) and δ15NNO3 values (r = -0.74) on a log scale, consistent with the increasing N release from livestock farming since the 1960s. In particular, the median value of δ15NNO3 rapidly increased to 9.2‰ in groundwater recharged between the late 1970s and early 1990s when N production exponentially increased, implying a significant effect of livestock farming after the 1980s. Groundwater quality is expected to deteriorate over the next several decades based on the groundwater ages (> 23.5 years), the increased N production from livestock farming, and the legacy effect of N. Long-term groundwater management plans (> 25 years) are required to decrease N loads in the study area, because it takes time for management practices to take effect. The study results are a good reference for groundwater management in regions with a source shift to livestock farming under intensive livestock production systems. Moreover, the chronological study using historical N production, groundwater age data, and dual nitrate isotopes can be applied to other regions with multiple N sources and their shifting for identifying sources and estimating time lags.

Kim|Seok Hee|SH|
Kim|Ho-Rim|HR|
Yu|Soonyoung|S|
Kang|Hyun-Ji|HJ|
Hyun|Ik-Hyun|IH|
Song|Young-Cheol|YC|
Kim|Hyunkoo|H|
Yun|Seong-Taek|ST|

Livestock farming
Legacy effect
Water management
CFCs dating and dual nitrate isotopes
Groundwater nitrate