Differential diagnosis of knee pain following a surgically induced lumbosacral plexus stretch injury. A case report.

Abstract: Background and Purpose: Knee joint biomechanics requires an understanding of lower extremity (LE) segmental interactions. In some cases, knee pain may arise as a result of altered LE biomechanics; while in other cases, knee pain may stem from other causes, such as a peripheral nerve injury. Case Description: A 33-year-old woman presented via direct access for physical therapist (PT) examination with a chief complaint of left knee pain. The day after undergoing a dilation and curettage (D&C) procedure the patient had an acute onset of gait dysfunction. Over the next few days, the patient developed left anterior knee pain (7/10 at worst) in addition to a significant change in physical functioning (Lower Extremity Functional Scale [LEFS] 38/80). Physical examination revealed left LE weakness, altered sensation, and an absent Achilles deep tendon reflex. Outcomes: The patient's presentation was consistent with a lumbosacral plexus stretch injury, with S1 being most affected. A physiatrist was consulted and recommended initiating PT treatment with bi-weekly re-examination. The 6-week (14 visits) re-examination revealed abolished left knee pain and improved physical functioning (LEFS 66/80). Conclusion: Stretch injuries are a known complication of lithotomy positioning. Knowledge of this and the addition of a thorough examination allowed the PT to identify the possible cause of the patient's abrupt onset of left LE dysfunction. Regardless of mode of patient access, screening for referral is crucial and may include referral or, as in this case, consultation with other professionals.

D000022:Abortion, Spontaneous
D000328:Adult
D003937:Diagnosis, Differential
D004185:Disability Evaluation
D005260:Female
D005684:Gait
D006801:Humans
D007049:Iatrogenic Disease
D007717:Knee
D008160:Lumbosacral Plexus
D009460:Neurologic Examination
D010147:Pain Measurement
D056888:Patient Positioning
D059348:Peripheral Nerve Injuries
D026741:Physical Therapy Modalities
D014592:Uterine Hemorrhage

nerve injury
dilation and curettage
gait dysfunction
weakness
Lithotomy position


Cerebral paragonimiasis: a retrospective analysis of 27 cases.

Abstract:
OBJECT
The authors retrospectively analyzed the clinical characteristics, existing problems, and treatment experiences in recently diagnosed cerebral paragonimiasis (CP) cases and sought to raise awareness of CP and to supply reference data for early diagnosis and treatment.

METHODS
Twenty-seven patients (22 male and 5 female; median age 20.3 years, range 4-47 years) with CP were diagnosed between September 2008 and September 2013. These diagnoses were confirmed by IgG enzyme-linked immunosorbent assays. Follow-up was performed in 24 cases for a period of 6-56 months.

RESULTS
Cerebral paragonimiasis accounted for 21.6% of paragonimiasis cases (27 of 125). The average duration from onset to praziquantel treatment was 69 days. All patients resided in rural areas. Twenty patients had positive lung results, which included visible lung lesions in 14 cases. The lesions were surgically removed in 8 of these cases. Twenty-four patients had high eosinophil counts (≥ 0.08 × 10(9)/L), and eosinophilic meningitis was noted in 17 cases. The rate of misdiagnosis and missed diagnosis was 30.4%. Most symptoms were markedly improved after treatment, but mild movement disorders combined with impaired memory and personality changes remained in a small number of patients.

CONCLUSIONS
Clinicians should be alert to the possibility of CP in young patients (4-16 years) with the primary symptoms of epilepsy and hemorrhage. Early diagnosis and timely treatment can reduce the need for surgery and further impairments to brain function. Liquid-based cytological examination of CSF and peripheral blood eosinophil counts can aid in differentiating CP from similar lesions.

Xia|Yong|Y| Ju|Yan|Y| Chen|Jing|J| You|Chao|C|

D020807:Central Nervous System Parasitic Infections

ELISA = enzyme-linked immunosorbent assay


Biokinetics of radiocesium depuration in marine fish inhabiting the vicinity of the Fukushima Dai-ichi Nuclear Power Plant.

Abstract: Radiocesium (134Cs and 137Cs) released from the Fukushima Dai-ichi Nuclear Power Plant (1FNPP) accident contaminated the fish inhabiting the port of 1FNPP. Radiocesium concentrations in some fishes, especially rockfish, have still remained at elevated levels, while concentrations in olive flounder have decreased in 2015 to the level which is close to the Japanese regulatory limit for seafood products (0.1 kBq kg-wet-1). In this study a dynamic food chain transfer model was applied to reconstruct radiocesium levels in olive flounder residing around the port area. As a result, the observed 137Cs concentrations in olive flounder collected from the port could be explained by the simulated values in the fish, using the seawater level records at the port entrance. The reconstructed maximum 134+137Cs concentration in olive flounder inhabiting the port area was 72 kB kg-wet-1 in July 2011 and the ecological half-life (EHL) was estimated as being 180 days during the period of 2014-2015. Short term simulation which assumed that the coastal water fish swam into the port during 1 month, demonstrated that the radiocesium level in the olive flounder may become equivalent to the depurated level in the fish which were initially contaminated. This result indicated that the increase of radiocesium levels in wandering fish is unlikely to change total radiocesium concentrations in the olive flounder. In this sense, the radiocesium levels in the olive flounder of the port area can be interpreted as being convergent in 2015, regardless of the differences in their contamination histories. On the other hand, the higher 137Cs concentrations in fat greenling, compared to the olive flounder, can be attributed to a history of exposure to the contaminated seawater and food at the inner area of the port, such as the shallow draft quay and seawall area. As a result of the reconstructed initial higher radiocesium concentration, constrained by exposure history at the inner area of the port, the depurated radiocesium concentration in fat greenling is still likely to be greater than the regulatory level in the port area in 2015.

Tateda|Yutaka|Y| Tsumune|Daisuke|D| Misumi|Kazuhiro|K| Aono|Tatsuo|T| Kanda|Jota|J| Ishimaru|Takashi|T|

Marine fish
Food chain transfer
(137)Cs
Dynamic biological compartment model
Fukushima reactor accident


Road Traffic Injury in Lagos, Nigeria: Assessing Prehospital Care.

Abstract:
Introduction Injuries are the third most important cause of overall deaths globally with one-quarter resulting from road traffic crashes. Majority of these deaths occur before arrival in the hospital and can be reduced with prompt and efficient prehospital care. The aim of this study was to highlight the burden of road traffic injury (RTI) in Lagos, Nigeria and assess the effectiveness of prehospital care, especially the role of Lagos State Ambulance Service (LASAMBUS) in providing initial care and transportation of the injured to the hospital.

METHODS
A three-year, retrospective review of road traffic injured patients seen at the Surgical Emergency Room (SER) of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria, from January 1, 2012 to December 31, 2014 was conducted. Parameters extracted from the Institution Trauma Registry included bio-data, date and time of injury, date and time of arrival in SER, host status, type of vehicle involved, and region(s) injured. Information on how patients came to the hospital and outcome in SER also were recorded. Results were analyzed using Statistical Package for Social Sciences (SPSS; IBM Corporation; Armonk, New York USA) version 16.

RESULTS
A total of 23,537 patients were seen during the study period. Among them, 16,024 (68.1%) had trauma. Road traffic crashes were responsible in 5,629 (35.0%) of trauma cases. Passengers constituted 42.0% of the injured, followed by pedestrians (34.0%). Four wheelers were the most frequent vehicle type involved (54.0%), followed by motor cycles (30.0%). Regions mainly affected were head and neck (40.0%) and lower limb (29.0%). Less than one-quarter (24.0%) presented to the emergency room within an hour, while one-third arrived between one and six hours following injury. Relatives brought 55.4%, followed by bystanders (21.4%). Only 2.3% had formal prehospital care and were brought to the hospital by LASAMBUS. They also had significantly shorter arrival time. One hundred and nine patients (1.9%) died in the emergency room while 235 bodies were brought in dead.

CONCLUSION
Less than three percent among the victims of road crashes had formal prehospital care and shorter hospital arrival time. Current facilities for emergency prehospital care in Lagos are inadequate and require improvement. Training lay first-responders, who bring the majority of the injured to hospital, in basic first-aid may improve prehospital care in Lagos. Ibrahim NA , Ajani AWO , Mustafa IA , Balogun RA , Oludara MA , Idowu OE , Solagberu BA . Road traffic injury in Lagos, Nigeria: assessing prehospital care. Prehosp Disaster Med. 2017;32(4):424-430.

Ibrahim|Nasiru A|NA|
Ajani|Abdul Wahab O|AWO|
Mustafa|Ibrahim A|IA|
Balogun|Rufai A|RA|
Oludara|Mobolaji A|MA|
Idowu|Olufemi E|OE|
Solagberu|Babatunde A|BA|

LASUTH Lagos State University Teaching Hospital


Chemical Structure-Antioxidant Activity Relationship of Water-Based Enzymatic Polymerized Rutin and Its Wound Healing Potential.

Abstract: The flavonoid rutin (RU) is a known antioxidant substance of plant origin. Its potential application in pharmaceutical and cosmetic fields is, however, limited, due to its low water solubility. This limitation can be overcome by polymerization of the phenolic RU into polyrutin (PR). In this work, an enzymatic polymerization of RU was performed in water, without the addition of organic solvents. Further, the chemical structure of PR was investigated using 1H NMR, and FTIR spectroscopy. Size-exclusion chromatography (SEC) was used to determine the molecular weight of PR, while its acid/base character was studied by potentiometric charge titrations. Additionally, this work investigated the antioxidant and free radical scavenging potential of PR with respect to its chemical structure, based on its ability to (i) scavenge non biological stable free radicals (ABTS), (ii) scavenge biologically important oxidants, such as O2•, NO•, and OH•, and (iii) chelate Fe2+. The influence of PR on fibroblast and HaCaT cell viability was evaluated to confirm the applicability of water soluble PR for wound healing application.

Pivec|Tanja|T|
Kargl|Rupert|R|
Maver|Uroš|U|
Bračič|Matej|M|
Elschner|Thomas|T|
Žagar|Ema|E|
Gradišnik|Lidija|L|
Kleinschek|Karin Stana|KS|

rutin
polyrutin
chemical structure
antioxidant activity
aqueous enzymatic polymerization


The Relationship between Birth Weight Discordance and Adverse Infant Mortality among Monozygotic and Dizygotic Twins in Japan, 1995-2008.

Abstract: Using vital statistics in Japan (1995-2008), 154,578 live-born twin pairs (128,236 monozygotic [MZ] and 180,920 dizygotic [DZ]) were identified. The proportion of severe discordance among live-born twin births was twice as high in Japanese than Caucasian infants. There were 1858 MZ and 1620 DZ infant deaths. Computation of the relationship between infant mortality rate and birth weight discordance among the twins was performed. Discordance levels were classified into seven groups: <5%, five groups from 5-9% to 25-29%, and ≥30%.The mortality rate was significantly higher in MZ than DZ twins for discordances except at 5-9% and 10-14%. The lowest rate for MZ twins was at 5-9% (7.5 per 1000 live twins) and significantly increased from 10-14% (9.4) to ≥30% (83.4), while the lowest rate for DZ twins was at <5% (6.7), which significantly increased at 10-14% (8.0) and from 25-29% (12.1) to ≥30% (35.5). The relationship was also computed in two gestational age groups (<28 and ≥28 weeks). For births at <28 weeks, three discordances (after 20-24%) in MZ twins were associated with adverse mortality rate. For births at ≥28 weeks, the same relationship was obtained after 10-14% in MZ and after 20-24% in DZ twins. The relationship from 2002 to 2008 showed that the mortality rates significantly increased after 10-14% for both types of twins. In conclusion, five discordance levels in MZ and three levels in DZ twins were associated with adverse mortality rates.

D001724:Birth Weight
D005865:Gestational Age
D049673:History, 20th Century
D049674:History, 21st Century
D006801:Humans
D007223:Infant
D007226:Infant Mortality
D007564:Japan
D014429:Twins, Dizygotic
D014430:Twins, Monozygotic

birth weight discordance
Infant mortality
twins
gestational age


Frontal Fibers Connecting the Superior Frontal Gyrus to Broca Area: A Corticocortical Evoked Potential Study.

Abstract:
BACKGROUND
The frontal aslant tract is a deep frontal pathway connecting the superior frontal gyrus (SFG) to Broca area. This fiber is assumed to be associated with language functions, especially speech initiation and spontaneity. The aim of this study was to electrophysiologically investigate this network using corticocortical evoked potentials (CCEPs).

METHODS
This study enrolled 8 patients with brain tumors or medically intractable focal epilepsies who underwent frontal craniotomy over the language-dominant side. All patients underwent CCEP recordings during tumor resection or during invasive evaluation for epilepsy surgery. Alternating 1-Hz electrical stimuli were delivered to pars opercularis (pO) and pars triangularis (pT), corresponding to Broca area, and SFG via the subdural grid electrodes with intensity of 10 mA. Electrocorticograms from SFG and pO/pT time-locked to 50 stimuli were averaged in each trial to obtain CCEP responses.

RESULTS
In all patients, stimulation of pO/pT induced CCEP responses in SFG. CCEP responses were recorded in lateral SFG in 5 patients and in supplementary motor areas in 4 patients. Reciprocality was observed in 7 patients in the stimulation of SFG. CCEP responses were significantly faster at SFG from pO/pT than at pO/pT from SFG (Wilcoxon signed rank test, P = 0.028).

CONCLUSIONS
The present study demonstrated a corticocortical network connecting Broca areas and SFG in a reciprocal manner. Our findings might provide new insight into language and motor integration.

Ookawa|Satoshi|S| Enatsu|Rei|R| Kanno|Aya|A| Ochi|Satoko|S| Akiyama|Yukinori|Y| Kobayashi|Tamaki|T| Yamao|Yukihiro|Y| Kikuchi|Takayuki|T| Matsumoto|Riki|R| Kunieda|Takeharu|T| Mikuni|Nobuhiro|N|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D001932:Brain Neoplasms
D065711:Broca Area
D056324:Diffusion Tensor Imaging
D004828:Epilepsies, Partial
D005071:Evoked Potentials
D005260:Female
D006801:Humans
D007806:Language Disorders
D008279:Magnetic Resonance Imaging
D008297:Male
D008875:Middle Aged
D011183:Postoperative Complications
D017397:Prefrontal Cortex
D011930:Reaction Time
D055815:Young Adult

Superior frontal gyrus
Broca area
Frontal aslant tract
Supplementary motor area
Electric cortical stimulation


Comparison of Medium Manganese Steel and Q345 Steel on Corrosion Behavior in a 3.5 wt % NaCl Solution.

Abstract: A cyclic wet/dry accelerated corrosion test was used to compare the corrosion behavior of medium-Mn steel and Q345 steel. In terms of scanning electron microscope (SEM), using X-ray diffraction (XRD), electron probe microanalysis (EPMA), X-ray photoelectron spectroscopy (XPS), and analysis of the corrosion process, the results showed that the medium-Mn steel did not exhibit higher corrosion resistance than Q345 steel due to the greater content of Mn-rich compounds in the rust layer. Moreover, the effect of a small amount of anti-corrosion elements in medium-manganese steel can regulate the corrosion rate. The conceptual model of the corrosion process of the medium-Mn steel in a 3.5 wt % NaCl solution is proposed.


Quantitative and Qualitative Antibody Responses to Immunization With the Pneumococcal Polysaccharide Vaccine in HIV-Infected Patients After Initiation of Antiretroviral Treatment: Results From a Randomized Clinical Trial.

Abstract:
BACKGROUND
Pneumococcal vaccination is recommended for human immunodeficiency virus-infected (HIV+) persons; the best timing for immunization with respect to initiation of antiretroviral therapy (ART) is unknown.

METHODS
Double-blind, placebo-controlled trial in HIV+ with CD4(+) T cells/µL (CD4) ≥ 200 randomized to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23) or placebo at enrollment, followed by placebo or PPV23, respectively, 9-12 months later (after ≥6 months of ART). Capsular polysaccharide-specific immunoglobin (Ig) G and IgM levels to serotypes 1, 3, 4, 6B, and 23F, and opsonophagocytic killing activity (OPA) to serotypes 6B and 23F were evaluated 1 month postvaccination.

RESULTS
One hundred seven subjects were enrolled, 72 (67.3%) were evaluable (36/group). Both groups had significant increases in pre- to 1-month postvaccination IgG levels, but negligible to IgM, and significant increases in OPA titers to serotype 6B but not to 23F. There were no significant differences between groups in serotype-specific IgM or IgG levels or OPA titers. For the combined groups, there was a significant correlation between serotype-specific IgG and OPA titers to 23F but not to 6B. There was no correlation between CD4, viral load and IgG responses.

CONCLUSIONS
In HIV+ with CD4 ≥ 200, delaying PPV23 until ≥6 months of ART does not improve responses and may lead to missed opportunities for immunization.

Rodriguez-Barradas|Maria C|MC|
Serpa|Jose A|JA|
Munjal|Iona|I|
Mendoza|Daniel|D|
Rueda|Adriana M|AM|
Mushtaq|Mahwish|M|
Pirofski|Liise-Anne|LA|

antibody
antiretroviral treatment
pneumococcal vaccine
HIV
pneumococcal capsular polysaccharides


Identifying conservation priorities for threatened Eastern Himalayan mammals.

Abstract: To augment mammal conservation in the Eastern Himalayan region, we assessed the resident 255 terrestrial mammal species and identified the 50 most threatened species based on conservation status, endemism, range size, and evolutionary distinctiveness. By using the spatial analysis package letsR and the complementarity core-area method in the conservation planning software Zonation, we assessed the current efficacy of their protection and identified priority conservation areas by comparing protected areas (PAs), land cover, and global ecoregion 2017 maps at a 100 × 100 m spatial scale. The 50 species that were most threatened, geographically restricted, and evolutionarily distinct faced a greater extinction risk than globally nonthreatened and wide-ranging species and species with several close relatives. Small, medium-sized, and data-deficient species faced extinction from inadequate protection in PAs relative to wide-ranging charismatic species. There was a mismatch between current PA distribution and priority areas for conservation of the 50 most endangered species. To protect these species, the skewed regional PA distribution would require expansion. Where possible, new PAs and transboundary reserves in the 35 priority areas we identified should be established. There are adequate remaining natural areas in which to expand current Eastern Himalayan PAs. Consolidation and expansion of PAs in the EH requires strengthening national and regional transboundary collaboration, formulating comprehensive regional land-use plans, diversifying conservation funding, and enhancing information sharing through a consolidated regional database.

D003247:Conservation of Natural Resources

mamífero pequeñom mamífero evolutivamente distintivo


The impact of pharmacist certification on the quality of chemotherapy in Japan.

Abstract: Background In the Japanese healthcare system, board certification not only maintains the quality of daily practice but is also required for hospitals to receive healthcare reimbursement. To date, no data on the effects of the board certification system in Japanese hospitals have been reported. Objective We performed a survey to clarify the impact of pharmacist certification on the quality of chemotherapy. Setting A nationwide mailing survey was conducted in Japan. Method We surveyed oncology pharmacists from 388 cancer designated hospitals (DHs) and 984 randomly selected general hospitals (GHs). Main outcome measure Multivariate analysis of factors for compliance with standard cancer chemotherapy to clarify the impact of pharmacist certification on the quality of chemotherapy. Results The response rate was 70.6 % (274/388) at the DHs and 43.4 % (428/984) at the GHs. Of the 13 different regimens, 66.1 % (181/274) of DHs and 64.7 % (277/428) of GHs reported having experienced either improper doses or intervals of drug administration. The median number of improper regimens was 1 at both the DHs (range 0-15) and GHs (range 0-22). We identified two groups of hospitals, those with two or more improper regimens and those with one improper regimen or less. Univariate analysis showed significant differences in the number of DHs (p < 0.01), performance of more than 10 chemotherapies per day (p < 0.05), presence of more than 400 beds (p < 0.01) and the professional qualifications of oncology pharmacists or medical oncologists. From multivariate analysis, significant differences were observed in certifications from the Japanese Society of Pharmacy Healthcare and Sciences certified Senior Oncology Pharmacist (odds ratio 0.29, p < 0.01) and the Japanese Society of Medical Oncology certified oncologist (odds ratio 0.48, p < 0.01). Conclusion Board certification was more prevalent in the designated (cancer specialist) hospitals than general hospitals and adherence to appropriate therapy was better when the DH was involved. Board certification was shown to be beneficial in terms of adherence to adequate chemotherapy.

Suzuki|Shinya|S| Sakurai|Hiroomi|H| Kawasumi|Kenji|K| Tahara|Makoto|M| Saito|Shinichiro|S| Endo|Kazushi|K|

Certification Chemotherapy Japan Specialization


Interventions to promote physical activity in older people with type 2 diabetes mellitus: a systematic review.

Abstract:
INTRODUCTION
Type 2 diabetes mellitus (T2DM) among people aged 60 years and above is a growing public health problem. Regular physical activity is one of the key elements in the management of T2DM. Recommendations suggest that older people with T2DM will benefit from regular physical activity for better disease control and delaying complications. Despite the known benefits, many remain sedentary. Hence, this review assessed interventions for promoting physical activity in persons aged 65 years and older with T2DM.

METHODS
A literature search was conducted using Ovid MEDLINE, PubMed, EMBASE, SPORTDiscus, and CINAHL databases to retrieve articles published between January 2000 and December 2012. Randomized controlled trials and quasi-experimental designs comparing different strategies to increase physical activity level in persons aged 65 years and older with T2DM were included. The methodological quality of studies was assessed.

RESULTS
Twenty-one eligible studies were reviewed, only six studies were rated as good quality and only one study specifically targeted persons aged 65 years and older. Personalized coaching, goal setting, peer support groups, use of technology, and physical activity monitors were proven to increase the level of physical activity. Incorporation of health behavior theories and follow-up supports also were successful strategies. However, the methodological quality and type of interventions promoting physical activity of the included studies in this review varied widely across the eligible studies.

CONCLUSION
Strategies that increased level of physical activity in persons with T2DM are evident but most studies focused on middle-aged persons and there was a lack of well-designed trials. Hence, more studies of satisfactory methodological quality with interventions promoting physical activity in older people are required.

physical activity
older people
type 2 diabetes mellitus
geriatric medicine
health promotion


Study on Demethoxycurcumin as a Promising Approach to Reverse Methicillin-Resistance of Staphylococcus aureus.

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) has always been a threatening pathogen. Research on phytochemical components that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigate the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and explore its possible mechanism for eliminating MRSA. The minimum inhibitory concentrations (MICs) of DMC against MRSA strains was determined by the broth microdilution method, and the results showed that the MIC of DMC was 62.5 μg/mL. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time-kill assay. The ATP synthase inhibitors were employed to block the metabolic ability of bacteria to explore their synergistic effect on the antibacterial ability of DMC. In addition, western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. As results, DMC hindered the translation of penicillin-binding protein 2a (PBP2a) and staphylococcal enterotoxin and reduced the transcription of related genes. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.

D015964:Gene Expression Regulation, Bacterial


Rationally Incorporated MoS2/SnS2 Nanoparticles on Graphene Sheets for Lithium-Ion and Sodium-Ion Batteries.

Abstract: Herein, we have designed and first synthesized a unique ternary hybrid structure by simultaneously growing SnS2 and MoS2 particles on graphene sheets (denoted as MoS2/SnS2-GS) via one-pot hydrothermal route. The charge incompatibility between MoO42- and graphene oxide with negative charged functional groups on surface can be compromised with the aid of Sn4+ cations, which renders the final formation of SnS2 and MoS2 on GS surface. This is the first report of the cohybridization of MoS2 and SnS2 with GS matrix from anionic and cationic precursors in the absence of premedication of graphene surface. When MoS2/SnS2-GS acts as anodes for lithium-ion batteries, the hybrids exhibit much better cycling stability than MoS2-GS and SnS2-GS counterparts. The compact adhesion of MoS2/SnS2 nanoparticles helps offset the undesired result of destruction of electrode materials resulting from volume expansion during repeated cycles. Furthermore, by combination with their synergetic effect on interface and the presence of discrepant asynchronous electrochemical reactions for SnS2 and MoS2, MoS2/SnS2-GS hybrids are endowed with improvement of electrochemical capabilities. Besides, they also showed outstanding Na-storage ability.


A Cable-Shaped Lithium Sulfur Battery.

Abstract: A carbon nanostructured hybrid fiber is developed by integrating mesoporous carbon and graphene oxide into aligned carbon nanotubes. This hybrid fiber is used as a 1D cathode to fabricate a new cable-shaped lithium-sulfur battery. The fiber cathode exhibits a decent specific capacity and lifespan, which makes the cable-shaped lithium-sulfur battery rank far ahead of other fiber-shaped batteries.

Fang|Xin|X| Weng|Wei|W| Ren|Jing|J| Peng|Huisheng|H|

nanostructures
hybrid fibers
carbon nanotubes
cable-shaped batteries
lithium sulphur batteries


Pharmacodynamics, pharmacokinetics and biodistribution of recombinant human N-acetylgalactosamine 4-sulfatase after 6months of therapy in cats using different IV infusion durations.

Abstract:
BACKGROUND
Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease characterized by an absence or marked reduction of lysosomal N-acetylgalactosamine-4-sulfatase activity. Affected individuals have widespread accumulation of unmetabolized glycosaminoglycan substrates leading to detrimental effects. Recombinant human N-acetylgalactosamine 4-sulfatase (rhASB) is an approved enzyme replacement therapy for patients with MPS VI. Despite the known efficacy of weekly 4-h rhASB infusions, some clinicians wish to treat patients using reduced infusion times. This study compared the pharmacodynamics, pharmacokinetics, and tissue biodistribution of rhASB when administered as 2- and 4-h intravenous infusions using a feline model of MPS VI.

METHODS
Study animals were MPS VI-affected cats that demonstrate clinical signs and biochemical derangements similar to human MPS VI patients. Beginning at age 4weeks, animals received weekly 2-h (N=6) or 4-h (N=6) IV infusions of rhASB for 26weeks (Naglazyme® [galsulfase] Solution for Intravenous Infusion; BioMarin Pharmaceutical, Inc.). The control group consisted of untreated MPS VI-affected cats (N=6). The pharmacokinetic parameters of plasma rhASB and urinary glycosaminoglycan were determined at weeks 13 and 26. Animals were euthanized 48h after the last infusion and tissue concentration of ASB, GAG and β-glucuronidase were measured in the liver, spleen, aorta, and kidney. Skeletal and ophthalmological evaluations were performed within 2weeks of euthanasia.

RESULTS
At week 13, the mean AUC0-t in animals treated with 4-h infusions was similar to 2-h infusions while the Cmax of the 4-h infusion was 50% of the 2-h infusion. By week 26, the mean AUC0-t of the 4-h infusion was 1.3-fold higher than the 2-h infusion (p<0.05) while Cmax of the 4-h infusion was 70% of the 2-h infusion (p<0.05). Among animals treated with 2- and 4-h infusions, there was no difference in urinary GAG excretion, tissue GAG storage, tissue galsulfase activity, and β-glucuronidase but all were significantly different than control animals (for each, p<0.001). Radiographic skeletal abnormality scores for animals were also similar for both treatment groups and significantly higher than control animals (p<0.001). There was no significant difference in corneal clouding scores among treated and untreated animals.

CONCLUSIONS
There was no significant difference in clinical outcomes when rhASB was administered to MPS VI affected cats as 2- and 4-h infusions over 26weeks. Additional studies may determine if shorter infusion times are appropriate for MPS VI patients without significant infusion-associated reactions.

Ruane|Therese|T|
Haskins|Mark|M|
Cheng|Alphonsus|A|
Wang|Ping|P|
Aguirre|Gustavo|G|
Knox|Van W Rafe|VW|
Qi|Yulan|Y|
Tompkins|Troy|T|
O'Neill|Charles A|CA|


Factors Related to Successful Energy Transmission of Focused Ultrasound through a Skull : A Study in Human Cadavers and Its Comparison with Clinical Experiences.

Abstract:
OBJECTIVE
Although magnetic resonance guided focused ultrasound (MRgFUS) has been used as minimally invasive and effective neurosurgical treatment, it exhibits some limitations, mainly related to acoustic properties of the skull barrier. This study was undertaken to identify skull characteristics that contribute to optimal ultrasonic energy transmission for MRgFUS procedures.

METHODS
For ex vivo skull experiments, various acoustic fields were measured under different conditions, using five non-embalmed cadaver skulls. For clinical skull analyses, brain computed tomography data of 46 patients who underwent MRgFUS ablations (18 unilateral thalamotomy, nine unilateral pallidotomy, and 19 bilateral capsulotomy) were retrospectively reviewed. Patients' skull factors and sonication parameters were comparatively analyzed with respect to the cadaveric skulls.

RESULTS
Skull experiments identified three important factors related skull penetration of ultrasound, including skull density ratio (SDR), skull volume, and incidence angle of the acoustic rays against the skull surface. In clinical results, SDR and skull volume correlated with maximal temperature (Tmax) and energy requirement to achieve Tmax (p<0.05). In addition, considering the incidence angle determined by brain target location, less energy was required to reach Tmax in the central, rather than lateral targets particularly when compared between thalamotomy and capsulotomy (p<0.05).

CONCLUSION
This study reconfirmed previously identified skull factors, including SDR and skull volume, for successful MRgFUS; it identified an additional factor, incidence angle of acoustic rays against the skull surface. To guarantee successful transcranial MRgFUS treatment without suffering these various skull issues, further technical improvements are required.

Jung|Na Young|NY|
Rachmilevitch|Itay|I|
Sibiger|Ohad|O|
Amar|Talia|T|
Zadicario|Eyal|E|
Chang|Jin Woo|JW|

High-intensity focused ultrasound ablation ∙ Skull ∙ Acoustics


Serial changes in vessel walls of renal arteries after catheter-based renal artery denervation: insights from volumetric computed tomography analysis.

Abstract:
Aim
Radiofrequency ablation of peri-arterial renal autonomic nerves has been studied as a potential therapeutic option for resistant hypertension. While recent clinical trials have reported its efficacy, there is paucity of data addressing the effects of the procedure on renal arteries, such as changes in vessel and lumen areas. Herein, the effect of atheroma burden on renal arteries after renal denervation was assessed using computed tomography (CT) imaging.

Materials and methods
Serial renal artery CT imaging was conducted in 38 patients from the EnligHTN™ I study, a prospective, multicenter study evaluating the efficacy of the EnligHTN multi-electrode radiofrequency ablation catheter in resistant hypertensive subjects. Cross-sectional images of renal arteries at 1 mm intervals were acquired using commercially available software (3mensio Structural Heart version 5.1). Vessel and lumen areas were manually traced in each image. Vessel wall volume (VWV) and percent vessel wall volume (P-VWV) were calculated. The measurements within the ablation (first 30 mm segments) and the non-ablation (subsequent 30 mm segment after the first bifurcation of renal arteries) zones were compared.

Results
On serial evaluation, greater increase in P-VWV and VWV was observed in the ablation zone (change in P-VWV, 6.7%±5.1% vs 3.6%±2.8%, P=0.001; change in VWV, 106.3±87.4 vs 23.0±18.2 mm3, P=0.001). Receiver-operating characteristic analysis demonstrated baseline P-VWV in the ablation zone >37.1% as an optimal cutoff value to predict its substantial progression after the procedure (area under the curve=0.88, sensitivity 89.8%, specificity 79.1%).

Conclusion
Change in vessel wall was greater within the segments receiving renal artery denervation. Baseline VWV predicted its substantial increase after the procedure. These observations suggest that atheroma burden within the renal arteries is a potential contributing factor to vascular changes after renal sympathetic denervation.

Kataoka|Yu|Y|
Delacroix|Sinny|S|
Sidharta|Samuel|S|
Andrews|Jordan|J|
Nicholls|Stephen J|SJ|
Tsioufis|Costas P|CP|
Papademetriou|Vasilios|V|
Worthley|Stephen G|SG|

renal artery
computed tomography
resistant hypertension
renal denervation
blood pressure


Neural circuits underlying tongue movements for the prey-catching behavior in frog: distribution of primary afferent terminals on motoneurons supplying the tongue.

Abstract: The hypoglossal motor nucleus is one of the efferent components of the neural network underlying the tongue prehension behavior of Ranid frogs. Although the appropriate pattern of the motor activity is determined by motor pattern generators, sensory inputs can modify the ongoing motor execution. Combination of fluorescent tracers were applied to investigate whether there are direct contacts between the afferent fibers of the trigeminal, facial, vestibular, glossopharyngeal-vagal, hypoglossal, second cervical spinal nerves and the hypoglossal motoneurons. Using confocal laser scanning microscope, we detected different number of close contacts from various sensory fibers, which were distributed unequally between the motoneurons innervating the protractor, retractor and inner muscles of the tongue. Based on the highest number of contacts and their closest location to the perikaryon, the glossopharyngeal-vagal nerves can exert the strongest effect on hypoglossal motoneurons and in agreement with earlier physiological results, they influence the protraction of the tongue. The second largest number of close appositions was provided by the hypoglossal and second cervical spinal afferents and they were located mostly on the proximal and middle parts of the dendrites of retractor motoneurons. Due to their small number and distal location, the trigeminal and vestibular terminals seem to have minor effects on direct activation of the hypoglossal motoneurons. We concluded that direct contacts between primary afferent terminals and hypoglossal motoneurons provide one of the possible morphological substrates of very quick feedback and feedforward modulation of the motor program during various stages of prey-catching behavior.

Kecskes|Szilvia|S| Matesz|Clara|C| Gaál|Botond|B| Birinyi|András|A|

D000344:Afferent Pathways
D000818:Animals
D003391:Cranial Nerves
D007002:Hypoglossal Nerve
D008526:Medulla Oblongata
D009043:Motor Activity
D009046:Motor Neurons
D011235:Predatory Behavior
D011898:Ranidae
D014059:Tongue

Hypoglossal motoneurons
Brainstem
Cranial nerves
Fluorescent labeling
Sensorimotor integration


Oxidized Phospholipids on Apolipoprotein B-100 and Recurrent Ischemic Events Following Stroke or Transient Ischemic Attack.

Abstract:
BACKGROUND
Biomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking.

OBJECTIVES
This study evaluated whether patients with prior cerebrovascular events and elevated levels of oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), but without prior coronary artery disease (CAD), are at risk for recurrent stroke and CAD events following high-dose statin therapy.

METHODS
In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, OxPL-apoB levels were measured in 4,385 patients with stroke or transient ischemic attack at baseline and in 3,106 patients at 5 years following randomization to placebo or 80 mg atorvastatin. The primary endpoint was the time from randomization to a second nonfatal or fatal stroke. Secondary endpoints included first major coronary events and any cardiovascular event.

RESULTS
Patients with recurrent stroke had higher baseline median OxPL-apoB levels than patients without (15.5 nmol/l vs. 11.6 nmol/l; p < 0.0001). After multivariable adjustment, elevated baseline OxPL-apoB predicted recurrent stroke (hazard ratio [HR]: 4.3; p < 0.0001), first major coronary events (HR: 4.0; p < 0.0001), and any cardiovascular event (HR: 4.4; p < 0.0001). These comparisons for any endpoint did not differ by treatment, shown as a nonsignificant interaction test. The net reclassification improvement, integrated discrimination improvement, and area under the receiver-operating characteristic curve (AUC) were all significantly improved by adding OxPL-apoB to the models, with ΔAUC +0.0505 (p < 0.0001) for recurrent stroke, ΔAUC +0.0409 (p < 0.0001) for first major coronary event, and ΔAUC +0.0791 (p < 0.0001) for any cardiovascular event.

CONCLUSIONS
Elevated OxPL-apoB levels predicted recurrent stroke and first major coronary events in patients with prior stroke or transient ischemic attack. The lack of statin-OxPL-apoB treatment interaction suggested that OxPLs might be statin-independent therapeutic targets to reduce risk of cardiovascular events. (Lipitor in the Prevention of Stroke, for Patients Who Have Had a Previous Stroke [SPARCL]; NCT00147602).

Byun|Young Sup|YS|
Yang|Xiaohong|X|
Bao|Weihang|W|
DeMicco|David|D|
Laskey|Rachel|R|
Witztum|Joseph L|JL|
Tsimikas|Sotirios|S|
|||

statin therapy
net reclassification improvement
integrated discrimination improvement
oxidation-specific epitope
risk factors


Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage.

Abstract: The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA)), transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency.

D002462:Cell Membrane
D002614:Chelating Agents
D003300:Copper
D017136:Ion Transport
D008129:Lolium
D008954:Models, Biological
D018515:Plant Leaves
D018517:Plant Roots

chelator membrane mechanism plant model phytoextraction amendment permeability


A Snapshot of Urban Adolescent Women's Contraceptive Knowledge at the Onset of a Community Long-Acting Reversible Contraceptive Promotion Initiative.

Abstract:
STUDY OBJECTIVE
To contextualize young women's knowledge and attitudes regarding contraception at the outset of an intervention promoting long-acting reversible contraceptive (LARC) use for teen pregnancy prevention.

DESIGN AND SETTING
Our intervention was on the basis of diffusion of innovation theory, and at the outset we were interested in likely early adopters' existing knowledge and attitudes toward contraception. This mixed methods study consisted of focus groups within positive youth development programs in Rochester, New York; we discussed young women's knowledge and sources of information for all US Food and Drug Administration-approved contraceptive methods.

PARTICIPANTS
Seven focus groups and 24 female adolescent participants aged 15-19 years.

INTERVENTIONS AND MAIN OUTCOME MEASURES
Quantitative ranking of all contraceptive methods; qualitative themes from focus group discussions.

RESULTS
Our findings showed a high level of knowledge about a select group of methods, which included LARC methods, and that participants received contraceptive information from peers and family. Participants had more concerns than positive impressions regarding the effectiveness, safety, practicality, and partner reception of the contraceptive methods, with the exception of the condom. Quantitatively, the condom received the highest average rating.

CONCLUSION
The importance of personal anecdotes in our findings supports the use of outreach and information campaigns; providing medically accurate information and spreading positive personal anecdotes will be key to improving young women's impressions of the safety and acceptability of LARC use. This snapshot of contraceptive knowledge indicates that young women can be mature, informed consumers of sexual and reproductive health care, and through diffusion of innovation could be key players in promoting the most effective means of pregnancy prevention.

Greenberg|Katherine Blumoff|KB|
Jenks|Sara Catherine|SC|
Piazza|Nina|N|
Malibiran|Beatriz Ramos|BR|
Aligne|C Andrew|CA|

D007722:Health Knowledge, Attitudes, Practice

Adolescent
Contraception
Diffusion of innovation
Health education


Antioxidative effect of melatonin on cryopreserved chicken semen.

Abstract: This is a unique study because is the first time we are adding melatonin into an extender in order to determine its influence on cryopreserved chicken semen. The primary focus of our present study was to evaluate the influence of different concentrations of Melatonin on cryopreserved chicken semen. Semen samples were allocated into four treatments, being one control and three different combinations of antioxidants and after the freeze-thaw operation, the sperm motility, plasma membrane integrity, acrosome integrity, endogenous enzymes (GSH-Px, CAT, SOD), MDA and ROS of chicken spermatozoa were all evaluated. The collection of the semen samples was from 40 Arbor Acre roosters and this procedure was repeated twice a week and then mixed in an extender that contained different MEL treatments as follows: a diluent without MEL (control, M 0), a diluent comprising 0.125 mg/mL (M 0.125) 0.25 mg/mL, (M 0.25) and 0.5 mg/mL (M 0.5). It was revealed that the supplementation of the base extender with an optimal 0.25 mg/mL MEL led to a higher significant difference in the motility of chicken sperm (P < 0.01), higher acrosome integrity (P < 0.05) and a higher plasma membrane integrity (P < 0.01) when compared to the control group at post-thaw. Furthermore, when compared to the control group, 0.25 mg/mL MEL addition into the extender significantly enhanced the activity of endogenous enzymes (GSH-Px, CAT, and SOD) in the chicken spermatozoa at post-thaw (P < 0.05). Moreover, 0.5 mg/mL MEL supplementation into the extender enhanced the GSH-Px activity in the chicken spermatozoa when compared with the control group (P < 0.05) at post-thaw. In contrast, the addition of 0.25 mg/mL MEL into the extender resulted in a significantly lower MDA in comparison to the 0.125 mg/mL, 0.5 mg/mL MEL treatment group and the control group (P < 0.05). Also, compared to the control group, MEL concentration of 0.125 mg/mL and 0.5 mg/mL MEL into the extender resulted in a significantly low ROS concentration (P < 0.05) but the addition of 0.25 mg/mL MEL concentration resulted in a significantly lower ROS level when compared to the control group (P < 0.01). In summary, MEL improved the quality of cryopreserved chicken sperm quality by decreasing oxidative stress level and the most optimal concentration was 0.25 mg/mL.

Appiah|Michael Osei|MO|
He|Beibei|B|
Lu|Wenfa|W|
Wang|Jun|J|

Melatonin Cryopreservation Chicken Spermatozoa


Outcomes after Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Patients with Primary Immunodeficiency Diseases.

Abstract: Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/μL CD4+ and 1000/μL CD3+ cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Fernandes|Juliana Folloni|JF|
Nichele|Samantha|S|
Arcuri|Leonardo Javier|LJ|
Ribeiro|Lisandro|L|
Zamperlini-Netto|Gabriele|G|
Loth|Gisele|G|
Rodrigues|Ana Luiza Melo|ALM|
Kuwahara|Cilmara|C|
Koliski|Adriana|A|
Trennepohl|Joanna|J|
Garcia|Julia Lopes|JL|
Daudt|Liane Esteves|LE|
Seber|Adriana|A|
Gomes|Alessandra Araujo|AA|
Fasth|Anders|A|
Pasquini|Ricardo|R|
Hamerschlak|Nelson|N|
Rocha|Vanderson|V|
Bonfim|Carmem|C|

D018380:Hematopoietic Stem Cell Transplantation

Outcomes
Post-transplantation cyclophosphamide
Primary immunodeficiency disease
Haploidentical transplantation


Synthesis, characterization and anti-inflammatory properties of karanjin (Pongamia pinnata seed) and its derivatives.

Abstract: Karanja (Pongamia pinnata) is a medicinal tree used in the Indian traditional ayurvedic system for treating several ailments. The seeds contain a unique furano-flavonoid karanjin, which has shown to possess many medicinal properties. Its usage at the clinical level is affected due to poor solubility and absorption. In the present investigation, molecular modifications of karanjin were attempted and evaluated their effect on anti-inflammatory activity. Firstly, Karanja ketone was obtained from karanjin by hydrolysis, and it was converted into karanja ketone oxime. The oxime undergoes Beckmann rearrangement and cyclized to yield furano benzoxazole (karanja oxazole). The new derivatives were purified with >95% purity (HPLC) and spectrally characterized (HR-MS, FTIR, and NMR). Among the test compounds, karanja ketone oxime exhibited higher antioxidant activity with an IC50 value of 360 µg/ml (DPPH). Soy lipoxygenase-1 (LOX-1) inhibitory activity of oxime was higher (IC50 = 65.4 µM) than other compounds. Fluorescence studies showed that oxime had higher quenching capacity with a Qmax of 76.3% and a binding constant of 0.9 × 105 M-1 for soy LOX-1. In-silico interaction studies showed that karanja ketone oxime had the least binding energy of -5.76 kcal/mol with LOX-1 by forming two hydrogen bonds with hydrophobic amino acids Leu 390 and Gly 392. The compounds were evaluated for their acute anti-inflammatory activity by the paw and ear edema in the rat model. Karanjin inhibits paw edema and ear edema by 34.13% and 51.13%, respectively, whereas the derivatives inhibited by 45-57 % and 70-76.8%. This study reports a rational approach to synthesize karanjin derivatives with considerable anti-inflammatory properties, both in-vitro and in-vivo.

Rekha|M J|MJ|
Bettadaiah|B K|BK|
Muthukumar|S P|SP|
Govindaraju|K|K|

Anti-inflammatory property
Karanjin
Karanja ketone
Oxime
Oxazole
Lipoxygenase


Early Cerebral Infarction after Aneurysmal Subarachnoid Hemorrhage.

Abstract: Aneurysmal subarachnoid hemorrhage (SAH) is a serious disease with high case fatality and morbidity. Early cerebral infarction has been suggested as a risk factor for poor outcome. We aimed to assess the pattern of early and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage. We prospectively enrolled consecutive aneurysmal subarachnoid hemorrhage (SAH) patients presenting to an academic neurosurgical referral center (Prince of Wales Hospital, the Chinese University of Hong Kong) in Hong Kong. Cerebral infarction occurred in 24 (48 %) patients, in which 14 (28 %) had early cerebral infarction and 14 (28 %) had delayed cerebral infarction. Early anterior cerebral infarction occurred in a similar proportion of anterior and posterior circulation aneurysms (24 % vs. 21 %), whereas posterior circulation aneurysm patients had a higher proportion of early posterior cerebral infarction compared with anterior circulation aneurysm patients (18 % vs. 2 %). In conclusion, early cerebral infarction was common and different from delayed cerebral infarction.

Wong|George Kwok Chu|GK|
Leung|Joyce Hoi Ying|JH|
Yu|Janice Wong Li|JW|
Lam|Sandy Wai|SW|
Chan|Emily Kit Ying|EK|
Poon|Wai Sang|WS|
Abrigo|Jill|J|
Siu|Deyond Yun Woon|DY|

D000328:Adult
D020520:Brain Infarction
D002544:Cerebral Infarction
D015331:Cohort Studies
D018450:Disease Progression
D057510:Endovascular Procedures
D005260:Female
D006723:Hong Kong
D006801:Humans
D008297:Male
D008875:Middle Aged
D015999:Multivariate Analysis
D019635:Neurosurgical Procedures
D011446:Prospective Studies
D012307:Risk Factors
D013345:Subarachnoid Hemorrhage
D013525:Surgical Instruments
D013997:Time Factors
D014057:Tomography, X-Ray Computed

Cerebral infarction
Aneurysm
Subarachnoid hemorrhage
Stroke


In vitro models for peripheral nerve regeneration.

Abstract: The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. However, the clinical outcome after nerve lesions is often far from satisfactory and the functional recovery is almost never complete. Therefore, a number of therapeutic approaches are being investigated, ranging from local delivery of trophic factors and other molecules to bioactive biomaterials and complex nerve prostheses. Translation of the new therapeutic approaches to the patient always requires a final pre-clinical step using in vivo animal models. The need to limit as much as possible animal use in biomedical research, however, makes the preliminary use of in vitro models mandatory from an ethical point of view. In this article, the different types of in vitro models available today for the study of peripheral nerve regeneration have been ranked by adopting a three-step stair model based on their increasing ethical impact: (i) cell line-based models, which raise no ethical concern; (ii) primary cell-based models, which have low ethical impact as animal use, although necessary, is limited; and (iii) organotypic ex vivo-based models, which raise moderate ethical concerns as the use of laboratory animals is required although with much lower impact on animal wellbeing in comparison to in vivo models of peripheral nerve regeneration. This article aims to help researchers in selecting the best experimental approach for their scientific goals driven by the 'Three Rs' (3Rs) rules (Replacement, Reduction or Refinement of animal use in research) for scientific research.

Geuna|S|S| Raimondo|S|S| Fregnan|F|F| Haastert-Talini|K|K| Grothe|C|C|

D000818:Animals
D046508:Culture Techniques
D006801:Humans
D009416:Nerve Regeneration
D059348:Peripheral Nerve Injuries
D010525:Peripheral Nerves

Schwann cell
cell line
neuron
organotypic culture
primary culture


The 2018 update of the American College of Physicians glycaemic management recommendations: An invitation to continued inertia?

Abstract: The management of type 2 diabetes has become increasingly controversial. Tight control has been advocated for years; however, there was a recent revision published by the American College of Physicians in which limitations were made to liberalize glycaemic goals for most diabetics, targeting a level between 7% and 8%. In recent years, the evolution of diabetes care has been such that more potent drugs, with low risk of hypoglycaemia when used in the absence of insulin or secretagogues, have made their way into the market place. Use of such agents has made it easier to achieve greater glycaemic control reasonably safely. Unfortunately, it appears that there has been a significant amount of inertia over the past decade, which continues to persist. Relaxing the glycaemic control targets, as recommended by the American College of Physicians, may only help to propagate this inertia.

D048909:Diabetes Complications
D003924:Diabetes Mellitus, Type 2
D016903:Drug Monitoring
D004359:Drug Therapy, Combination
D006442:Glycated Hemoglobin A
D006801:Humans
D006943:Hyperglycemia
D007003:Hypoglycemia
D007004:Hypoglycemic Agents
D007328:Insulin
D017410:Practice Guidelines as Topic
D010818:Practice Patterns, Physicians'
D057285:Precision Medicine
D014481:United States

type 2 diabetes
Canagliflozin
antidiabetic drug
basal insulin
beta cell function
diabetes complications


Confirmatory Factor Analysis of the Patient Version of the Working Alliance Inventory--Short Form Revised.

Abstract: The working alliance concerns the quality of collaboration between patient and therapist in psychotherapy. One of the most widely used scales for measuring the working alliance is the Working Alliance Inventory (WAI). For the patient-rated version, the short form developed by Hatcher and Gillaspy (WAI-SR) has shown the best psychometric properties. In two confirmatory factor analyses of the WAI-SR, approximate fit indices were within commonly accepted norms, but the likelihood ratio chi-square test showed significant ill-fit. The present study used Bayesian structural equations modeling with zero mean and small variance priors to test the factor structure of the WAI-SR in three different samples (one American and two Swedish; N = 235, 634, and 234). Results indicated that maximum likelihood confirmatory factor analysis showed poor model fit because of the assumption of exactly zero residual correlations. When residual correlations were estimated using small variance priors, model fit was excellent. A two-factor model had the best psychometric properties. Strong measurement invariance was shown between the two Swedish samples and weak factorial invariance between the Swedish and American samples. The most important limitation concerns the limited knowledge on when the assumption of residual correlations being small enough to be considered trivial is violated.

Falkenström|Fredrik|F|
Hatcher|Robert L|RL|
Holmqvist|Rolf|R|

confirmatory factor analysis
Working Alliance Inventory
Bayesian structural equations modeling
measurement invariance


lncRNA DLX6-AS1 Promotes Proliferation of Laryngeal Cancer Cells by Targeting the miR-26a/TRPC3 Pathway.

Abstract:
Purpose
Laryngeal cancer is the most prevalent tumor type in head and neck cancers. Early diagnosis is considered as an important strategy for improving prognosis. The lncRNA DLX6-AS1 has been shown to modulate tumor phenotypes in several types of cancer, but the role of DLX6-AS1 in laryngeal cancer and its concrete mechanisms are not clear.

Methods
Tissue samples from laryngeal cancer patients and corresponding clinical data were used for detailed analysis. The laryngeal cancer cell lines HEp-2 and Tu-177 were studied. Cell proliferation, ROS production, mitochondrial respiratory function, intracellular and mitochondrial calcium influx were assessed. Western blotting, quantitative RT-PCR and luciferase assays were used to analyze the interactions. A xenografted tumor model was established to analyze the effects of DLX6-AS1 on tumor growth in vivo.

Results
lncRNA DLX6-AS1 had increased expression in tumor tissues compared with adjacent normal tissues and in higher clinical stages compared with lower stages, which was associated with poor prognosis. In detail, DLX6-AS1 knockdown decreased cell proliferation and affected key mitochondrial metabolic parameters in both HEp-2 and Tu-177 cells. Moreover, DLX6-AS1 knockdown suppressed TRPC3-mediated mitochondrial calcium uptake and ROS production. Furthermore, miR-26a functioned as a link between these two molecules, as it could be absorbed by DLX6-AS1 and thus regulated the levels of TRPC3. Finally, the DLX6-AS1/miR-26a/TRPC3 axis modulated laryngeal cancer proliferation both in vitro and in vivo.

Conclusion
This study provides new evidence that a novel lncRNA, DLX6-AS1, regulates mitochondrial calcium homeostasis, respiration and tumor proliferation via modulating the miR-26a/TRPC3 axis in laryngeal cancer.

Liu|Yan|Y| Liu|Xinyi|X| Zhang|Xiaofeng|X| Deng|Jinhu|J| Zhang|Jian|J| Xing|Hao|H|


Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis.

Abstract:
BACKGROUND
The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa.

MATERIALS AND METHODS
A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR-), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model.

RESULTS
With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR-, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria.

CONCLUSIONS
The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.

Qin|Zhiqiang|Z| Yao|Jianxiang|J| Xu|Luwei|L| Xu|Zheng|Z| Ge|Yuzheng|Y| Zhou|Liuhua|L| Zhao|Feng|F| Jia|Ruipeng|R|

D000951:Antigens, Neoplasm
D014408:Biomarkers, Tumor
D006801:Humans
D008297:Male
D016017:Odds Ratio
D011471:Prostatic Neoplasms
D012372:ROC Curve
D012680:Sensitivity and Specificity

Prostate cancer, familial [Supplementary Concept]

prostate cancer antigen 3, human [Supplementary Concept]


A flexible multi-species genome-wide 60K SNP chip developed from pooled resequencing of 240 Eucalyptus tree genomes across 12 species.

Abstract: We used whole genome resequencing of pooled individuals to develop a high-density single-nucleotide polymorphism (SNP) chip for Eucalyptus. Genomes of 240 trees of 12 species were sequenced at 3.5× each, and 46 997 586 raw SNP variants were subject to multivariable filtering metrics toward a multispecies, genome-wide distributed chip content. Of the 60 904 SNPs on the chip, 59 222 were genotyped and 51 204 were polymorphic across 14 Eucalyptus species, providing a 96% genome-wide coverage with 1 SNP/12-20 kb, and 47 069 SNPs at ≤ 10 kb from 30 444 of the 33 917 genes in the Eucalyptus genome. Given the EUChip60K multi-species genotyping flexibility, we show that both the sample size and taxonomic composition of cluster files impact heterozygous call specificity and sensitivity by benchmarking against 'gold standard' genotypes derived from deeply sequenced individual tree genomes. Thousands of SNPs were shared across species, likely representing ancient variants arisen before the split of these taxa, hinting to a recent eucalypt radiation. We show that the variable SNP filtering constraints allowed coverage of the entire site frequency spectrum, mitigating SNP ascertainment bias. The EUChip60K represents an outstanding tool with which to address population genomics questions in Eucalyptus and to empower genomic selection, GWAS and the broader study of complex trait variation in eucalypts.

Silva-Junior|Orzenil B|OB|
Faria|Danielle A|DA|
Grattapaglia|Dario|D|

D020411:Oligonucleotide Array Sequence Analysis

single-nucleotide polymorphism (SNP) ascertainment bias


Impact of community pharmacist-led interventions in chronic disease management on clinical, utilization, and economic outcomes: An umbrella review.

Abstract:
BACKGROUND
Chronic disease represents a significant burden to the United States (US) health care system, with approximately 50% of all adults in the US having one or more chronic disease conditions. Pharmacist-led chronic disease management interventions are of special interest since 80% of medical treatments involve the use of prescription drugs. Moreover, community pharmacists are among the most accessible health care professionals to provide care for populations with chronic diseases. The impact of care provided by community pharmacists isn't well defined, with interventions taking on diverse forms with varied effects on outcomes.

OBJECTIVE
The purpose of this review is to summarize evidence from secondary literature on community pharmacist-led chronic disease management interventions and the impact on clinical, utilization, and economic outcomes.

METHODS
We conducted a systematic search of systematic reviews, meta-analyses, and narrative reviews using MEDLINE via PubMed, EMBASE.com and Cochrane Library databases published between January 1, 2007 and October 17, 2017. The following data were extracted: citation details, review type, number of primary studies included, disease state, description of the intervention, outcomes assessed, and results.

RESULTS
Our search strategy retrieved 2296 titles and abstracts of which 15 references met our inclusion criteria. Selected articles covered 7 main diseases -diabetes, asthma, chronic obstructive pulmonary disease (COPD), hypertension, heart failure, hyperlipidemia, and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Community pharmacist-led interventions mostly consisted of patient consultations and education. In diabetes, interventions achieved significant reductions in hemoglobin A1c, total cholesterol, and low-density lipoprotein (LDL). Reviews also reported favorable reductions in blood pressure, improved medication adherence and reduced readmission rates in patients with heart failure, improved lung function in patients with respiratory conditions, and increased medication adherence in those with HIV/AIDs. Literature reporting economic and utilization outcomes were limited and mostly focused on pharmacy interventions in diabetes. In some cases, community pharmacy services demonstrated a decrease in medical and health care costs in patients with diabetes.

CONCLUSION
We found that community pharmacists can improve clinical outcomes in a wide array of chronic diseases, including diabetes, hyperlipidemia, HIV/AIDS, cardiovascular and respiratory diseases. More robust studies are needed to further assess the impact of specific interventions on economic and utilization outcomes.

Newman|Terri V|TV|
San-Juan-Rodriguez|Alvaro|A|
Parekh|Natasha|N|
Swart|Elizabeth C S|ECS|
Klein-Fedyshin|Michele|M|
Shrank|William H|WH|
Hernandez|Inmaculada|I|

Chronic disease
Disease management
Community pharmacy services
Population health


Noncovalent Bonds through Sigma and Pi-Hole Located on the Same Molecule. Guiding Principles and Comparisons.

Abstract: Over the last years, scientific interest in noncovalent interactions based on the presence of electron-depleted regions called σ-holes or π-holes has markedly accelerated. Their high directionality and strength, comparable to hydrogen bonds, has been documented in many fields of modern chemistry. The current review gathers and digests recent results concerning these bonds, with a focus on those systems where both σ and π-holes are present on the same molecule. The underlying principles guiding the bonding in both sorts of interactions are discussed, and the trends that emerge from recent work offer a guide as to how one might design systems that allow multiple noncovalent bonds to occur simultaneously, or that prefer one bond type over another.

chalcogen bond
cooperativity
halogen bond
molecular electrostatic potential
pnicogen bond
tetrel bond


Signaling Heterogeneity is Defined by Pathway Architecture and Intercellular Variability in Protein Expression.

Abstract: Insulin's activation of PI3K/Akt signaling, stimulates glucose uptake by enhancing delivery of GLUT4 to the cell surface. Here we examined the origins of intercellular heterogeneity in insulin signaling. Akt activation alone accounted for ~25% of the variance in GLUT4, indicating that additional sources of variance exist. The Akt and GLUT4 responses were highly reproducible within the same cell, suggesting the variance is between cells (extrinsic) and not within cells (intrinsic). Generalized mechanistic models (supported by experimental observations) demonstrated that the correlation between the steady-state levels of two measured signaling processes decreases with increasing distance from each other and that intercellular variation in protein expression (as an example of extrinsic variance) is sufficient to account for the variance in and between Akt and GLUT4. Thus, the response of a population to insulin signaling is underpinned by considerable single-cell heterogeneity that is largely driven by variance in gene/protein expression between cells.

Norris|Dougall|D|
Yang|Pengyi|P|
Shin|Sung-Young|SY|
Kearney|Alison L|AL|
Kim|Hani Jieun|HJ|
Geddes|Thomas|T|
Senior|Alistair M|AM|
Fazakerley|Daniel J|DJ|
Nguyen|Lan K|LK|
James|David E|DE|
Burchfield|James G|JG|

Cell Biology
Experimental Models in Systems Biology
Mathematical Biosciences
Systems Biology


Global trends in the extent of death scene investigation performed for sudden and unexpected death of infant (SUDI) cases: A systematic review.

Abstract: Sudden unexpected death of infants (SUDI) is the rapid and unexpected death of an infant aged less than 1year old. These deaths are referred for a medico-legal investigation to establish cause of death. National and regional protocols for the investigation of SUDI cases have been established in some countries and these typically include a death scene investigation component. However, there is a paucity of literature detailing the nature and extent of death scene investigation protocols. A systematic review was conducted to review the scope of death scene investigation of SUDI cases worldwide. Relevant articles (n=74) were identified by searching four literature databases, three discipline-specific journals, as well as each article's reference list, until saturation was reached. Of the 16 countries represented by the included articles, seven made specific reference to the standardised protocol used, which included photography, interviews and/or scene re-enactments. The remaining 54 studies appeared to include a subset of these analyses during death scene investigation, which varied between countries, and between SUDI admissions. This may be attributed to the differing socio-economic standings of countries, and the resources available. Only four studies were from developing countries, three of which originated from South Africa. Overall, where a standardised death scene investigation was performed, it added value to the post-mortem investigation; as such, death scene investigation should be encouraged in SUDI investigation. To this end, protocols should be established nationally, and contain core analyses, which could be expanded depending on the needs and resources of the country.

Bennett|Tracy|T|
Martin|Lorna J|LJ|
Heathfield|Laura J|LJ|

Centers for Disease Control and Prevention


A novel approach for antibody nanocarriers development through hydrophobic ion-pairing complexation.

Abstract: IgG-Fab fragment, a model antibody protein was hydrophobically modified by a novel approach of ion-pairing complexation. Three different sulphated ion-pairing agents were utilised including sodium dodecyl sulphate, taurocholic acid and dextran sulphate (DS). The formations of hydrophobic ion-pairing (HIP) complexes were dependant on pH and molar ratio of ion-pairing agent to Fab. Aqueous solubilities of HIP complexes were very low compared to Fab alone. In particular, when dextran sulphate was added as ion-pairing agent, formed Fab:DS HIP complexes were least soluble in water. Further, nanoparticles (NPs) loaded with drug and Fab:DS HIP complex were prepared and characterised with respect to encapsulation efficiency and size. We observed significant improvement in encapsulation efficiency for Fab:DS HIP complex-loaded nanoparticles. This study demonstrates a novel approach of formulating antibody-loaded nanoparticles which can also be employed for delivery of large antibodies.

Patel|Ashaben|A|
Gaudana|Ripal|R|
Mitra|Ashim K|AK|

D057927:Hydrophobic and Hydrophilic Interactions

hydrophobic ion-pairing complex
IgG-Fab fragment
protein
dextran sulphate
nanoparticles
Antibody fragment


Analysis for Protein Glycosylation of Pattern Recognition Receptors in Plants.

Abstract: Recognition of molecules typical of microbes or aberrant cellular states, termed microbe- or danger-associated molecular patterns (MAMPs/DAMPs), respectively, provides an important step in plant and animal innate immunity. In plants, pattern recognition receptors (PRRs) identified to date are limited to membrane-associated proteins, of which the majority has an extracellular leucine-rich repeat (LRR) or lysine-motif (LysM) domain. These PRRs undergo quality control (QC) in the Endoplasmic Reticulum (ER) that is dependent on Asn (N)-linked glycosylation (Glc3Man9GlcNAc2 conjugation) of their extracellular domain. In Arabidopsis, genetic studies have revealed that a subset of these PRRs require an intact N-glycosylation pathway in the ER for their biogenesis and function. Here, we describe methods for immunoblot-based detection of protein glycosylation states in plants.

Endoplasmic Reticulum quality control (ERQC)


Connexin hemichannels contribute to spontaneous electrical activity in the human fetal cortex.

Abstract: Before the human cortex is able to process sensory information, young postmitotic neurons must maintain occasional bursts of action-potential firing to attract and keep synaptic contacts, to drive gene expression, and to transition to mature membrane properties. Before birth, human subplate (SP) neurons are spontaneously active, displaying bursts of electrical activity (plateau depolarizations with action potentials). Using whole-cell recordings in acute cortical slices, we investigated the source of this early activity. The spontaneous depolarizations in human SP neurons at midgestation (17-23 gestational weeks) were not completely eliminated by tetrodotoxin--a drug that blocks action potential firing and network activity--or by antagonists of glutamatergic, GABAergic, or glycinergic synaptic transmission. We then turned our focus away from standard chemical synapses to connexin-based gap junctions and hemichannels. PCR and immunohistochemical analysis identified the presence of connexins (Cx26/Cx32/Cx36) in the human fetal cortex. However, the connexin-positive cells were not found in clusters but, rather, were dispersed in the SP zone. Also, gap junction-permeable dyes did not diffuse to neighboring cells, suggesting that SP neurons were not strongly coupled to other cells at this age. Application of the gap junction and hemichannel inhibitors octanol, flufenamic acid, and carbenoxolone significantly blocked spontaneous activity. The putative hemichannel antagonist lanthanum alone was a potent inhibitor of the spontaneous activity. Together, these data suggest that connexin hemichannels contribute to spontaneous depolarizations in the human fetal cortex during the second trimester of gestation.

Moore|Anna R|AR|
Zhou|Wen-Liang|WL|
Sirois|Carissa L|CL|
Belinsky|Glenn S|GS|
Zecevic|Nada|N|
Antic|Srdjan D|SD|

GABA
UP states
brain development
glutamate
preterm infants


Structural insight into the rearrangement of the switch I region in GTP-bound G12A K-Ras.

Abstract: K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism, is activated when it undergoes a conformation change upon binding GTP and is deactivated following the hydrolysis of GTP to GDP. Hydrolysis of GTP in water is accelerated by coordination to K-Ras, where GTP adopts a high-energy conformation approaching the transition state. The G12A mutation reduces intrinsic K-Ras GTP hydrolysis by an unexplained mechanism. Here, crystal structures of G12A K-Ras in complex with GDP, GTP, GTPγS and GppNHp, and of Q61A K-Ras in complex with GDP, are reported. In the G12A K-Ras-GTP complex, the switch I region undergoes a significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP γ-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants.

Xu|Shenyuan|S|0000-0002-9903-1944
Long|Brian N|BN|
Boris|Gabriel H|GH|
Chen|Anqi|A|
Ni|Shuisong|S|
Kennedy|Michael A|MA|

G12A K-Ras
K-Ras
apoptosis
GTP hydrolysis
Q61A K-Ras
precatalytic state
cancer cell regulation
cell growth regulation


Nurse opinions about initiating spiritual conversation and prayer in patient care.

Abstract:
AIM
The aim of this study was to understand nurses' opinions about initiating spiritual or religious conversation during patient care and to measure how these perspectives are associated with demographic, religious and work-related characteristics.

BACKGROUND
Nurses are expected to provide spiritual care and do so in diverse ways. Little is known about how nurses think about initiating spiritual or religious discourse.

DESIGN
Cross-sectional, quantitative.

METHODS
Online survey methods allowed data collection from 445 nurses. The survey, accessed from the homepage of the Journal of Christian Nursing for 6 months beginning June 2015, included scales measuring various facets of religiosity, and items assessing nurse opinions about introducing spirituality or religion during patient care and demographic and work-related variables. Variables showing significant associations with Nurse Opinion items in bivariate analyses were examined using binary logistic regression.

RESULTS
About 90% of participants believed it appropriate to initiate conversation about spirituality/religion and nearly three-quarters thought it appropriate to self-disclose spirituality/religion or offer prayer under certain circumstances or anytime. All personal religiosity indicators except tentativeness of belief were found to be associated with responses to Nurse Opinion items. That is, higher religiosity was associated with opinion one could initiate such conversations, whereas lower religiosity was associated with waiting for patients to initiate. Nurses working in a faith-based organization were 276% more likely to believe they could initiate such conversation and 153% more likely to think they could initiate an offer of prayer.

CONCLUSION
Nurse religiosity and work environment were associated with nurse opinions about initiating spiritual/religious discourse with patients.

spirituality
conversation
prayer
spiritual care
survey methods
religion
nurses/midwives/nursing
self-disclosure


Towards the In-silico Design of New HSP90 Inhibitors: Molecular Docking and 3D-QSAR CoMFA Studies of Tetrahydropyrido [4, 3-d] Pyrimidine Derivatives as HSP90 Inhibitors.

Abstract:
BACKGROUND
HSP90 is necessary for the conformational maturation of proteins, proteins disaggregation, folding newly synthesized peptides and the refolding of denatured proteins. The inhibition of HSP90 leads to proteasomal degradations of client proteins that finally kill cancer cells.

METHODS
In this research, molecular docking and comparative molecular field analysis (CoMFA) were used to investigate the interactions of tetrahydropyrido[4,3-d]pyrimidine derivatives with the N-terminal domain binding site of the HSP90 and predicting their inhibitory activities.

RESULTS
A CoMFA model with five components and q2 of 0.81 was developed. R2 for training and test sets were 0.96 and 0.79, respectively. Based on extracted Contour maps for this CoMFA model, three new inhibitors with greater pIC50 with respect to the greatest active molecule in the data-set were designed by modifying molecule m45. Molecule m45 and designed inhibitors were docked to the N-terminal domain binding site of the HSP90. Designed inhibitors obtained lower binding energy with respect to m45.

CONCLUSION
Based on extracted CoMFA contour maps, bulky substituents are favored for the R1 group and in R3 group, short and bulky substituents increase the activity of molecules. Less bulky and longer substituents are favored for R2. The molecular docking analysis of compound m45 with the N-terminal domain binding site of the HSP90 show hydroxyl group on phenyl ring is necessary to form hydrogen bonding with hydrophilic residues in binding site and a conserved water molecule. Molecule m45 has Pi-Sigma interaction with phenyl ring in the side chain of Phenylalanine 138 via isopropyl substituent on meta position of the phenyl ring. Also, Molecule m45 forms carbon-hydrogen bond with oxygen atoms at the side chain of Aspartic acid 54 and Asparagine 51 via its dimethylamine group. Others are Van der Waals interactions.

HSP90 inhibitor
molecular docking
CoMFA
Tetrahydropyrido [4, 3-d] pyrimidine
cytoplasm
polypeptide chains.


Occurrence of aflatoxin M1 in urines from rural and urban adult cohorts in Bangladesh.

Abstract: Aflatoxins are important mycotoxins produced by Aspergillus flavus and A. parasiticus, moulds which contaminate mainly grains and nuts, especially in hot and humid climate. Presence of aflatoxin B1 (AFB1), the most toxic one and a potent hepatocarcinogen, has been reported in food and feed in Bangladesh and raised concerns about mycotoxin exposure in the population. Biomonitoring provides the best approach to assess human exposure from various sources and by all routes. Part of the ingested AFB1 is converted in the body to aflatoxin M1 (AFM1), a metabolite that has served as biomarker of AFB1 exposure, as it is excreted in urine, and thus enables non-invasive sampling, a relevant aspect in field studies. This investigation measured the AFM1 concentration in urines collected from adult residents of a rural (n = 52) and an urban (n = 43) area in the Rajshahi district of Bangladesh. The urinary levels of AFM1 were determined by enzyme-linked immunosorbent assay. AFM1 was detected in 46 % of all urine samples at a range of 31-348 pg/mL. The median and mean concentration of AFM1 in urine was 61 and 80 ± 60 pg/mL, respectively. A significant difference (p < 0.05) was found at the mean level of AFM1 between the rural (99 ± 71 pg/mL) and urban (54 ± 15 pg/mL) cohort. Urinary AFM1 levels did not show significant correlations with food frequency data or age, gender and body mass index of the participants. Among them, the highest mean AFM1 level (101 ± 71 pg/mL) was observed in the 50-60 years age group. In conclusion, detection frequency and urinary AFM1 levels in the Bangladeshi adults support concerns regarding their dietary exposure to AFB1. These first data warrant further biomarker-based studies in children and in cohorts of other parts of the country.

Aflatoxin M1
Mycotoxins
Aflatoxin B1
Exposure
Biomarker


Associations between implementation of Project Lazarus and opioid analgesic dispensing and buprenorphine utilization in North Carolina, 2009-2014.

Abstract:
BACKGROUND
Project Lazarus (PL) is a seven-strategy, community-coalition-based intervention designed to reduce opioid overdose and dependence. The seven strategies include: community education, provider education, hospital emergency department policy change, diversion control, support programs for patients with pain, naloxone policies, and addiction treatment expansion. PL was originally developed in Wilkes County, NC. It was made available to all counties in North Carolina starting in March 2013 with funding of up to $34,400 per county per year. We examined the association between PL implementation and 1) overall dispensing rate of opioid analgesics, and 2) utilization of buprenorphine. Buprenorphine is often used in connection with medication assisted treatment (MAT) for opioid dependence.

METHODS
Observational interrupted time series analysis of 100 counties over 2009-2014 (n = 7200 county-months) in North Carolina. The intervention period was March 2013-December 2014. 74 of 100 counties implemented the intervention. Exposure data sources comprised process surveys, training records, Prescription Drug Monitoring Program (PDMP) data, and methadone treatment program quality data. Outcomes were PDMP-derived counts of opioid prescriptions and buprenorphine patients. Incidence Rate Ratios were estimated with adjusted GEE Poisson regression models of all seven PL strategies.

RESULTS
In adjusted models, diversion control efforts were positively associated with increased dispensing of opioid analgesics (IRR: 1.06; 95% CI: 1.03, 1.09). None of the other PL strategies were associated with reduced prescribing of opioid analgesics. Support programs for patients with pain were associated with a non-significant decrease in buprenorphine utilization (IRR: 0.93; 95% CI: 0.85, 1.02), but addiction treatment expansion efforts were associated with no change in buprenorphine utilization (IRR: 0.98; 95% CI: 0.91, 1.06).

CONCLUSIONS
Implementation of PL strategies did not appreciably reduce opioid dispensing and did not increase buprenorphine utilization. These results are consistent with previous findings of limited impact of PL strategies on overdose morbidity and mortality. Future studies should analyze the uptake of MAT using a more expansive view of institutional barriers, treating community coalition activity around MAT as an effect modifier.

Opioids
Buprenorphine
Overdose
MAT
Interrupted time series
PDMP
Community coalitions
Evaluation
Prevention


Studies on interaction of norbixin with DNA: multispectroscopic and in silico analysis.

Abstract: The interaction of food colorant norbixin with calf thymus DNA (CTDNA) was investigated through UV-Visible spectroscopy, Fourier Transform Infrared (FTIR), Circular Dichroism (CD), Nuclear Magnetic Resonance (NMR), DNA melting studies, electrophoretic analysis, histological staining technique and molecular docking studies. The results indicated that norbixin interacted with CTDNA by partial intercalation mode. The binding constant (K) of norbixin with CTDNA was calculated to be 5.08×10(5) Mol(-1) L. FTIR and CD studies were coupled with (1)H NMR spectra revealed that norbixin intercalates partially and binds to the groove's, phosphate group, deoxyribose sugar of DNA and also induces conformational transition of B-form to A-form DNA. Agarose gel electrophoretic and histological staining technique results further prove that, norbixin specifically binds to the DNA in the cell. Moreover, molecular docking studies on the specific binding of norbixin with CTDNA have exhibited lowest conformation energy score of -3.2. Therefore, this food colorant has the ability to interact with DNA and it could emerge as a promising class of natural DNA targeted therapeutic.

Anantharaman|Amrita|A|
Priya|Rajendra Rao|RR|
Hemachandran|Hridya|H|
Sivaramakrishna|Akella|A|
Babu|Subramanian|S|
Siva|Ramamoorthy|R|

D066244:Proton Magnetic Resonance Spectroscopy

D017550:Spectroscopy, Fourier Transform Infrared

Interaction
Norbixin
DNA
In silico analysis
Apocarotenoid
Spectroscopic


Recent advances in managing and understanding uveitis.

Abstract: Uveitis is a sight-threatening disease entity with intraocular inflammation that arises from various causes. It mainly affects working-age individuals and may lead to irreversible visual loss if not treated properly in a timely manner. This article reviews recent advances in the management and understanding of uveitis since 2014, including treatment with new immunosuppressive therapies that use biological agents, local therapy with steroid implants, and imaging studies for the evaluation of uveitis.

uveitis
immunosuppressive therapy
ocular implants
optical coherence tomography (OCT)


A novel scoring model to predict benefit of additional induction chemotherapy to concurrent chemoradiotherapy in stage II-IVa nasopharyngeal carcinoma.

Abstract:
OBJECTIVES
Induction chemotherapy (IC) is gaining recognition for the treatment of nasopharyngeal carcinoma (NPC). We aimed to develop a model to predict benefit from additional IC to concurrent chemoradiotherapy (CCRT).

MATERIALS AND METHODS
From an NPC-specific database, 7413 patients with stage II-IVa disease who received CCRT with or without IC were included. Distant metastasis-free survival (DMFS) was the primary outcome and benefit from IC was evaluated by adjusted hazard ratio. Interaction terms between IC and other prognostic factors were identified in multivariate Cox model, and IC benefit score (ICBS) was calculated based on β coefficients from the Cox model.

RESULTS
Nodal category, overall stage, and pre-treatment plasma Epstein-Barr virus DNA (log transformed as continuous variable) interacted with IC and determined ICBS. ICBS could discriminate patients who benefited differently from IC in terms of DMFS well, especially for patients with high and low ICBS. As for patients with medium ICBS, predictive performance of ICBS seemed reduced.

CONCLUSIONS
Based on the ICBS model, we proposed a decision-making process to help in clinical practice. Multi-institutional and prospective studies are warranted to further validate our findings.

Peng|Liang|L| Chen|Yu-Pei|YP| Xu|Cheng|C| Tang|Ling-Long|LL| Chen|Lei|L| Lin|Ai-Hua|AH| Liu|Xu|X| Sun|Ying|Y| Ma|Jun|J|

D000328:Adult
D000073888:Cell-Free Nucleic Acids
D059248:Chemoradiotherapy
D000066491:Clinical Decision-Making
D004279:DNA, Viral
D018572:Disease-Free Survival
D020031:Epstein-Barr Virus Infections
D005260:Female
D005500:Follow-Up Studies
D004854:Herpesvirus 4, Human
D006801:Humans
D060828:Induction Chemotherapy
D053208:Kaplan-Meier Estimate
D008297:Male
D008875:Middle Aged
D008954:Models, Biological
D000077274:Nasopharyngeal Carcinoma
D009303:Nasopharyngeal Neoplasms
D009367:Neoplasm Staging
D018579:Patient Selection
D011379:Prognosis
D016016:Proportional Hazards Models
D012189:Retrospective Studies

Induction chemotherapy
Nasopharyngeal carcinoma
Distant metastasis-free survival
Benefit prediction model
Interaction effect
Prognostic index


Association between male pattern baldness and testicular germ cell tumor: a meta-analysis.

Abstract:
BACKGROUND
The relationship between male pattern baldness and incidence of testicular cancer remains inconclusive. Hence, we performed the present meta-analysis based on all eligible case-control studies.

METHODS
A comprehensive literature search was performed in July 30th 2018 based on PUBMED, EMBASE and Web of science database. Pooled odds ratio(OR) and its 95% confidence intervals (95% CIs) was calculated with a DerSimonian and Laird random-effects.

RESULTS
The pooled results were included in this meta-analysis. Overall, We have demonstrated statistically signification between baldness(any pattern) and testicular cancer was identified (OR: 0.61, 95% CI:0.50-0.74). There was no obvious heterogeneity across included studies (P = 0.22 for heterogeneity, I2 = 30%). When subgroup analysis by types of baldness, We found a statistically significant association was observed that baldness(I-VII) might become a protective factor for the risk of testicular germ cell tumor(TGCT). There was no definite connection between alopecia and the different types of TGCT.

CONCLUSION
Individuals with any pattern baldness may have a decreased risk of testicular cancer, all of analyses studies are warranted to confirm our preliminary findings. According to subgroup analysis of different hair loss grades, we found that 2 stage(II) hair loss can decrease more strongly testicular cancer risk than any other grades. Despite of our findings, We still need further researches to advance knowledge in this field.

Zhou|Jiatong|J| Xia|Shuai|S| Li|Tao|T| Liu|Ranlu|R|

D009373:Neoplasms, Germ Cell and Embryonal

Male pattern baldness
Testicular germ cell tumor
Meta-analysis
Risk


Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541-750).

Abstract: The first historically documented pandemic caused by Yersinia pestis began as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although paleogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacterium's spread, diversity, and genetic history over the course of the pandemic. To elucidate the microevolution of the bacterium during this time period, we screened human remains from 21 sites in Austria, Britain, Germany, France, and Spain for Y. pestis DNA and reconstructed eight genomes. We present a methodological approach assessing single-nucleotide polymorphisms (SNPs) in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis on the eight reconstructed genomes reveals the existence of previously undocumented Y. pestis diversity during the sixth to eighth centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as the parallel occurrence of multiple derived strains in central and southern France, Spain, and southern Germany. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45-kb genomic region in the most recent First Pandemic strains affecting two virulence factors, intriguingly overlapping with a deletion found in 17th- to 18th-century genomes of the Second Pandemic.

Keller|Marcel|M|0000-0001-9668-6817
Spyrou|Maria A|MA|
Scheib|Christiana L|CL|
Neumann|Gunnar U|GU|
Kröpelin|Andreas|A|
Haas-Gebhard|Brigitte|B|
Päffgen|Bernd|B|
Haberstroh|Jochen|J|
Ribera I Lacomba|Albert|A|
Raynaud|Claude|C|
Cessford|Craig|C|
Durand|Raphaël|R|
Stadler|Peter|P|
Nägele|Kathrin|K|
Bates|Jessica S|JS|
Trautmann|Bernd|B|
Inskip|Sarah A|SA|
Peters|Joris|J|
Robb|John E|JE|
Kivisild|Toomas|T|0000-0002-6297-7808
Castex|Dominique|D|
McCormick|Michael|M|
Bos|Kirsten I|KI|
Harbeck|Michaela|M|
Herbig|Alexander|A|0000-0003-1176-1166
Krause|Johannes|J|0000-0001-9144-3920

Justinianic Plague
Anglo-Saxons
Merovingians
ancient DNA
bacterial evolution


Development of a scoliotic spine model for biomechanical in vitro studies.

Abstract:
BACKGROUND
In vitro experiments are important to compare surgical treatments. Especially new implants need preclinical evaluation. However, in vitro experiments with scoliotic specimens are impossible because they are not available. The purpose of this study was to develop an in vitro scoliosis model with cadaveric calf spine specimens, which may serve as a surrogate for human scoliotic spines.

METHODS
Six cadaveric calf spine specimens (T8-L6) were modified in three different steps to create a thoracolumbar scoliosis, convex to the right. First, all intervertebral discs received a nucleotomy. In the second step the cavity was filled with silicone. The silicone hardened in a bend position to obtain an asymmetrical nucleus. Finally, a wedge profile of the vertebral bodies was achieved by unilateral horizontal cuts (T9-L5), followed by spreading and fixation. Flexibility tests in a spine tester were performed in all motion planes with the original spine and after the different steps during the creation of the model.

FINDINGS
A Cobb angle >40° in the frontal plane could be achieved. Additionally, the vertebrae showed an axial rotation to the convex side. The range of motion increased due to the nucleotomy, decreased slightly after replacement with silicone, and decreased below the values of the intact spine after producing the wedge shape of the vertebrae. In each loading direction there was no significant asymmetry in the motion behavior.

INTERPRETATION
This study suggests a method to modify a straight spine specimen into a scoliotic one, which can be used for biomechanical in vitro experiments.

Wilke|Hans-Joachim|HJ| Mathes|Barbara|B| Midderhoff|Stefan|S| Graf|Nicolas|N|

Scoliosis model
Calf spine
Biomechanical test
In vitro test


Data management and wearables in older adults: A systematic review.

Abstract:
BACKGROUND
Wearable trackers as research or clinical tools are increasingly used to support the care of older adults, due to their practicality in self-monitoring and potential to promote healthy lifestyle behaviours. However, there is limited understanding of appropriate data collection and analysis methods in different contexts.

AIM
To summarise evidence on wearable data generation and management in older adults, focusing on physical activity (PA), electrocardiogram (ECG), and vital signs monitoring. In addition to examine the accuracy and utility of wearable trackers in the care of older people.

METHODS
A systematic search of CINAHL, MEDLINE, PubMed and a manual search were conducted. Twenty studies on the use of wearable trackers by older adults met the inclusion criteria.

RESULTS
Methodological designs for data collection and analysis were heterogeneous, with diverse definitions of wear and no-wear time, the number and type of valid days, and proprietary algorithms. Wearable trackers had adequate accuracy for measuring step counts, moderate to vigorous physical activity (MVPA), ECG and heart rate (HR), but not for respiratory rate. Participants reported ease of use and had high-level adherence over daily long-term use. Moreover, wearable trackers encouraged users to increase their daily level of physical activity and decrease waist circumference, facilitating atrial fibrillation (AF) diagnoses and predicting length of stay.

CONCLUSION
Wearable trackers are multi-dimensional technologies offering a viable and promising approach for sustained and scaled monitoring of older people's health. Frameworks and/or guidelines, including standards for the design, data management and application of use specifically for older adults, are required to enhance validity and reliability.

Alharbi|Muaddi|M| Straiton|Nicola|N| Smith|Sidney|S| Neubeck|Lis|L| Gallagher|Robyn|R|

Wearable
Older
Tracker
Physical activity
Monitor
Sensor