Casualties.
Privation and disease have mainly killed soldiers until very recently. Now that enemy action predominates, faster and better control of bleeding and infection before and during evacuation spares ever more lives today. This essay focuses on psychological war wounds, placing them in the context of military casualties. The surgeon's concepts of 'primary' wounds in war, and of would 'complications' and 'contamination', serve as models for psychological and moral injury in war. 'Psychological injury' is explained and preferred to 'Post-Traumatic Stress Disorder', being less stigmatizing and more faithful to the phenomenon. Primary psychological injury equates to the direct damage done by a bullet; the complications - for example, alcohol abuse - equate to hemorrhage and infection. Two current senses of 'moral injury' equate to wound contamination. As with physical wounds, it is the complications and contamination of mental wounds that most often kill service members or veterans, or blight their lives.


Validation of the Brazilian version of the patient-determined disease steps scale in persons with multiple sclerosis.
The present study translated and adapted the Brazilian version of the Patient-Determined Disease Steps (PDDS) scale and tested its validity and reproducibility in Brazilian persons with multiple sclerosis (MS). The PDDS underwent translation and back-translation procedures for producing a Brazilian Portuguese version of the PDDS (PDDS/BR). Sixty-three patients with MS (48 females) completed the PDDS/BR and underwent a neurological examination for generation of Expanded Disability Status Scale (EDSS) scores. Participants further performed the following tests: Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), six-minute walk test (6MWT), Nine Hole Peg (9HPT), and Symbol Digit Modalities Test (SDMT). Construct validity of PDDS/BR scores was determined by Spearman correlation with EDSS, and comparison of correlations between PDDS/BR and EDSS with the functional tests. We examined overall correct classification of disability categories (i.e., mild, moderate, or severe disability) by the PDDS/BR in relation to the EDSS. Test-retest reproducibility of PDDS/BR scores was examined in a subsample of 31 participants after 15 days. There was a strong relationship between the PDDS/BR and EDSS scores (ρ = 0.723, p < 0.05). The correlations with TUG, T25FW, 6MWT, and 9HPT were comparable for the PDDS/BR and EDSS scores. Overall correct classification of disability categories by the PDDS/BR was 79.3%. Results indicated excellent test-retest reproducibility for the PDDS/BR (Intraclass Correlation Coefficient= 0.911, 95% CI: 0.685-0.918). The PDDS/BR scores provide a valid and reliable assessment of mobility disability and may be used by researchers and neurologists to assess disability status in Brazilians with MS.


Physical studies of lanthanide binding to concanavalin A.
The binding of lanthanide ions to concanavalin A has been studied using circular dichroic, magnetic circular dichroic and fluorescence spectroscopies. A Scatchard analysis of the fluorescence enhancement of Tb3+ binding reveal the presence of two classes of sites. One strong binding site (S3) is present per protomer which is not affected by addition of transition metals or calcium. There are at least three additional weak binding sites per protomer, one of which may be S1. There is virtually no energy transfer from Tb3+ to Co2+ in cobalt-substituted concanavalin A. The S3 site, therefore, must be at least 39 A distant from S1. The circular dichroic spectrum of Co2+ concanavalin A is altered by addition of Gd3+ in a manner consistent with competition for S1. The magnetic circular dichroic spectrum of Pr3+ bound to concanavalin A is not affected by excess Ca2+ or the addition of specific carbohydrate effectors. There is no evidence for lanthanide ion binding to S2.


Quantifying consultations to medical specialties during psychiatric inpatient admissions in a Queensland tertiary hospital.
To identify and characterise medical consultations to psychiatric inpatients. Retrospective cross-sectional descriptive study of 451 psychiatric inpatients' electronic medical records between 1 January and 30 June 2021 with descriptive statistics. Thirty one percent (n = 131) of inpatients required medical consultation, with 382 total consultations including ward call. Half (57.9%) were telephone advice. Main consulting specialties were general medicine (25%), anaesthetics (12%), neurology (9.9%), cardiology (6.5%) and endocrinology (6.2%). Almost all (99.0%) consultations resulted in documented management plans. This is the first Australian descriptive study quantifying and characterising psychiatric inpatient consultation requests. Physical and psychiatric healthcare integration requires ongoing efforts, including improved referral pathways.


Coats-like Vasculopathy in Inherited Retinal Disease: Prevalence, Characteristics, Genetics, and Management.
To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV). Multicenter retrospective cohort study. A total of 67 patients with IRD-related CLV. Review of clinical notes, ophthalmic imaging, and molecular diagnosis from 2 international centers. Visual function, retinal imaging, management, and response to treatment were evaluated and correlated. The prevalence of IRD-related CLV was 0.5%; 54% of patients had isolated retinitis pigmentosa (RP), 21% had early-onset severe retinal dystrophy, and less frequent presentations were syndromic RP, sector RP, cone-rod dystrophy, achromatopsia, PAX6-related dystrophy, and X-linked retinoschisis. The overall age of patients at CLV diagnosis was 30.7 ± 16.9 years (1-83). Twenty-one patients (31%) had unilateral CLV, and the most common retinal features were telangiectasia, exudates, and exudative retinal detachment (ERD) affecting the inferior and temporal retina. Macular edema/schisis was observed in 26% of the eyes, and ERD was observed in 63% of the eyes. Fifty-four patients (81%) had genetic testing, 40 of whom were molecularly solved. Sixty-six eyes (58%) were observed, 17 eyes (15%) were treated with a single modality, and 30 eyes (27%) had a combined approach. Thirty-five eyes (31%) were "good responders," 42 eyes (37%) were "poor responders," 22 eyes (19%) had low vision at baseline and were only observed, and 12 eyes (11%) did not have longitudinal assessment. Twenty-one observed eyes (62%) responded well versus 14 (33%) treated eyes. Final best-corrected visual acuity was significantly worse than baseline (P = 0.002); 40 patients (60%) lost 15 ETDRS letters or more over follow-up in 1 or both eyes, and 21 patients (31%) progressed to more advanced stages of visual impairment. Inherited retinal disease-related CLV is rare, sporadic, and mostly bilateral; there is no gender predominance, and it can occur in diverse types of IRD at any point of the disease, with a mean onset in the fourth decade of life. Patients with IRD-related CLV who have decreased initial visual acuity, ERD, CLV changes affecting 2 or more retinal quadrants, and CRB1-retinopathy may be at higher risk of a poor prognosis. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


The use of MRI in the investigation of lateral meniscal tear post medial unicompartmental knee replacement.
The evaluation of lateral knee pain in patients with a medial unicompartmental knee replacement (UKR) is complex. The native lateral compartment structures are prone to the same injuries as patients with normal knees. Historical reports of lateral meniscal injury post medial UKR have argued MRI evaluation is obsolete due to artefact caused by the prosthesis. We report a case of lateral meniscal injury in a patient two years after successful medial UKR. We identified the offending pathology via utilization of MRI scanners adopting metal artefact reduction sequences (MARS). The MARS MRI protocol helps clinicians accurately and non-invasively evaluate soft tissue structures in knees with metal prostheses. It also allows surgeons to accurately counsel patients and provides a higher degree of certainty in treating the pathology.


PREVALENCE OF OBSTRUCTIVE SLEEP APNEA DETERMINED BY THE WATCHPAT IN NONOBESE JAPANESE PATIENTS WITH POOR GLUCOSE CONTROL AND TYPE 2 DIABETES.
Diagnosing obstructive sleep apnea (OSA) usually involves high cost, patient inconvenience, and the need for examination at a specialized center. This study employed a portable, wearable, diagnostic device (WatchPAT) to investigate the prevalence of OSA in nonobese Japanese patients with type 2 diabetes. Patients with type 2 diabetes were tested for OSA over one night using the WatchPAT. Logistic regression analysis was used to estimate the odds ratios (ORs) of risk factors for OSA in nonobese subjects. A total of 200 eligible patients with type 2 diabetes were studied (64.5% men; aged 60.1 ± 13.6 years; body mass index [BMI], 26.3 ± 5.2 kg/m2). When OSA was defined as apnea-hypopnea index ≥5/hour, its prevalence was 80.5%. The prevalence of OSA in subjects with a BMI <20 kg/m2, ≥20 and <25 kg/m2, ≥25 and <30 kg/m2, and ≥30 kg/m2 was 38.9%, 73.5%, 86.5%, and 97.5%, respectively. The severity of OSA increased in proportion to BMI, especially when the BMI was >25 kg/m2. The prevalence of OSA was also high (66.3%) in normal-weight subjects (BMI <25 kg/m2). Furthermore, the serum triglyceride level (OR, 1.01; 95% confidence interval, 1.00 to 1.02; P = .042) was significantly related to OSA. A high prevalence of OSA was observed in this nonobese population of Japanese patients with type 2 diabetes. The triglyceride level was associated with OSA among nonobese patients. AHI = apnea-hypopnea Index; BMI = body mass index; CI = confidence interval; ESS = Epworth Sleepiness Scale; HbA1c = glycated hemoglobin; OR = odds ratio; OSA = obstructive sleep apnea; PAT = peripheral arterial tone; T2D = type 2 diabetes; TG = triglyceride.


In vitro histological and tetracycline staining properties of surface layer rat incisor enamel also reflect the cyclical nature of the maturation process.
Rat incisors cleaned of overlying enamel organ cells stain unevenly with several common histological stains producing two kinds of banding pattern. In one a pattern of widely spaced stained bands run in an oblique to transverse direction from a more apical level on the medial side to a more incisal level on the lateral side of each tooth. The pattern correlated directly with that produced by both in vivo and in vitro short-term tetracycline labelling in the same teeth: it also resembled the patterns previously demonstrated in a) horseradish peroxidase penetration into lateral intercellular spaces between maturation ameloblasts, b) the distribution of enamel labelling in vivo with 45Ca, c) of etching of enamel surfaces demineralized with EDTA with the glutaraldehyde fixed enamel organ in situ and d) in the distribution of smooth-ended and ruffled border types of cell specializations. We conclude that these bands demonstrate further and previously unrecognised aspects of the cyclical phenomena in enamel maturation-mineralization and show cyclical differences in the physico-chemical status of the organic matrix in the maturation process. A second, incremental growth type of banding pattern occurred at 200-225 micron intervals in the lower incisors and had the same distribution at the beginning and end of the maturation zone.


Granulomatous mastitis: Presentations, diagnosis, treatment and outcome in 206 patients from the north of Iran.
The aim of this study is to review the clinical presentations, diagnostic methods, treatment options and outcome of patients with Granulomatous Mastitis (GM). In a retrospective study, we indentified 206 women who met the required histological criteria of (GM). Thirty eight (18%) of these women had taken antibiotics before their diagnosis of GM. The most common symptoms in remaining 168 symptomatic women were breast mass. The most common ultrasonographic and mammographic finding was large irregular hypo echoic masses and an irregular mass, respectively. As a diagnostic tool, fine needle aspiration (FNA) was performed in 33 (19.5%) and core needle biopsy with or without ultrasound was done in 92 (55%) of patients while successful rate was 13 (39%) and 87 (94.5%), respectively. The remaining 43 (25.5%) of women underwent surgical excisions. Only 6 (3%) patients improved with antibiotics and 200 (97%) of women who did not respond to antibiotics, were treated with steroid and among them 144 (72%) improved. Treatment with combination of methotrexate and steroid was done in 56 (28%) patients and was effective in 40 (71%) of them. Sixteen (8%) patients were treated with a combination of steroid and bromocriptine which was effective in 5 (31%) patients. A wide surgical excision was performed in 11 (5.5%) patients who were nonresponsive to steroid and methotrexate and bromocriptine therapy. Our findings indicate that clinical and imaging findings of (GM) have overlapped with malignancy. The best diagnostic method is core needle biopsy. Corticosteroids are in the first line of treatment with a good therapeutic response.


[The participation of the neurons of the caudal ventrolateral area of the medulla oblongata in the cat in regulating vascular tonus].
Inhibition of the separate neuronal groups located in the caudal ventrolateral part of the cat medulla at different depths from the brain surface is followed by the development of unidirectional cardiohemodynamic reactions. Microinjection of 30 nl of 0.1 M solution of glycine in the chemosensitive area "L" at a depth not more than 700 microns is followed by an increase of the arterial pressure to 160-225%, presumably, due to enhancement of the total peripheral vascular resistance, the cardiac output and heart rate change insignificantly. Such direction of hemodynamic changes is due to activation of the neurogenic vascular tone. Data obtained give the possibility to appreciate investigated neuronal groups as tonically active, with an inhibitory influence on sympathetically activation of the vessels. The method of the retrograde axonal transport of HRP was used to determine monosynaptic projections from different neuronal pools of the caudal ventrolateral part of medulla to the subsolitary district of the reticular formation. The data obtained contribute to comprehension of mechanisms of interaction in the dorsal and ventral areas of the medulla participating in the regulation of the vascular tone.


[The expression of Sonic Hedgehog during late bell stage by Western Blot and in situ hybridization].
To investigate the expression and biological effect of Shh during late bell stage by morphological and semi-quantitative analysis. Tooth germs were selected from new born Bal b/c mouse (P1, P2, P3, P5, P7). Semi-quality of Shh was measured by Western Blot and the expression place and strength of Shh were observed by in situ hybridization. Shh was expressed in the ameloblast layer during late bell stage; the expression strength was high in secretive period and decreased with development; the active N-section was detectable before P3. Shh expresses specially in the ameloblast layer in late bell stage, and expression quality is related to the function of ameloblasts.


Changes in extracellular calcium concentration in the immature rat cerebral cortex during anoxia are not influenced by MK-801.
The extracellular calcium concentration ([Ca2+]ec) was recorded by calcium-sensitive microelectrodes in the parietal cortex of 9-11 day old rats during anoxia. During the first 10 min of anoxia, [Ca2+]ec increased from 1.1 mM to 1.5 +/- 0.23 mM, and thereafter it started to decrease reaching below basal level after around 13 min. The [Ca2+]ec decrease was either slow and continuous, or biphased with a rapid initial decrease followed by a continuous slow decrease. After 60 min of anoxia, the [Ca2+]ec had reached 0.2-0.3 mM. Changes in [Ca2+]ec in animals treated with the NMDA receptor antagonist MK-801 (0.3 mg/kg i.p.) did not display any significant differences compared to controls. Thus, the strong neuroprotective effect of MK-801 in ischemic situations in the immature brain can not be explained by a prevention of calcium entry during anoxic depolarization.


Plants as bioreactors: a comparative study suggests that Medicago truncatula is a promising production system.
Plants are emerging as a promising alternative to conventional platforms for the large-scale production of recombinant proteins. This field of research, known as molecular farming, is developing rapidly and several plant-derived recombinant proteins are already in advanced clinical trials. However, the full potential of molecular farming can only be realized if we gain a fundamental understanding of biological processes regulating the production and accumulation of functional recombinant proteins in plants. Recent studies indicate that species- and tissue-specific factors as well as plant physiology can have a significant impact on the amount and quality of the recombinant product. More detailed comparative studies are needed for each product, including the analysis of expression levels, biochemical properties, in vitro activity and subcellular localization. In this review we include the first results from an extensive comparative study in which the highly glycosylated enzyme phytase (from the fungus Aspergillus niger) was produced in different plant species (including tobacco and the model legume Medicago truncatula). Special emphasis is placed on M. truncatula, whose leaves accumulated the highest levels of active phytase. We discuss the potential of this species as a novel production host.


Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: report of an investigation.
In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.


Removal of hazardous chlorinated VOCs from aqueous solutions using novel ZSM-5 loaded PDMS/PVDF composite membrane consisting of three hydrophobic layers.
Hydrophobic polymer possesses significant potential for selective separation of volatile organic compounds (VOCs) from their aqueous solutions by pervaporation (PV). In the present study mixed matrix hydrophobic membranes of polydimethylsiloxane (PDMS) supported on polyvinylidenefluoride (PVDF) substrate were synthesized by incorporating hydrophobic inorganic ZSM-5 filler. The indigenous membranes were crosslinked with tetraethylorthosilicate (TEOS) for the extraction of volatile chlorinated hydrocarbons such as dichloromethane (DCM), trichloromethane (TCM), 1,2-dichloroethane (DCE), and 1,1,2,2-tetrachloroethane (TeCE), which pose serious environment threat and health hazard. Thermal stability, crosslinking, crystallinity, surface morphology and swelling characteristics of the indigenously developed membranes were determined by TGA, FTIR, XRD, SEM and sorption studies, respectively. Effect of operating parameters such as feed composition and filler concentration on separation performance in terms of flux and selectivity were determined. Flux of DCM, TCM, DCE and TeCE was found to be 0.166, 0.146, 0.141 and 0.06 kg m(-2)h(-1) with selectivity of 541, 1068, 917 and 15,000, respectively, for 20% ZSM-5 filled PDMS membrane for aqueous feeds containing 1.33% (w/v) DCM, 0.8% (w/v) TCM, 0.84% (w/v) DCE and 0.28% (w/v) TeCE in water. The membrane exhibited considerable feasibility for scale-up with significant potential for removal of hazardous chlorinated VOCs from aqueous solutions.


Skin tape stripping identifies gene transcript signature associated with allergic contact dermatitis.
Allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) are common skin conditions with an overlapping clinical and histological appearance, but distinct underlying mechanisms. Patch testing is the gold standard for ACD diagnosis, yet the interpretation of its results may be confounded by weak and varying macroscopic reactions. To examine whether gene transcript profiling of RNA sampled from patch tested patient skin by tape stripping (TS) could differentiate ACD from ICD and the baseline skin state (control) METHODS: Nine patients (seven females, two males; mean age 38.6 years, range 24-72 years) with confirmed ACD through patch testing were recruited. Total RNA was isolated from TS samples and relative transcript abundance was determined by quantitative real-time polymeraise chain reaction using 39 gene-specific primers. TS captured gene transcripts derived from diverse skin cell types, including not only keratinocytes, but also epidermal and dermal antigen-presenting cells. Among the genes analysed in transcript profiling, genes encoding epidermal barrier components and inflammatory mediators exhibited changes in transcript abundance in ACD skin compared to ICD or control skin. Our findings reveal the potential of skin TS for non-invasive biopsy during patch testing and molecular marker-based ACD diagnosis.


Peripheral BDNF Regulates Somatosensory-Sympathetic Coupling in Brachial Plexus Avulsion-Induced Neuropathic Pain.
Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.


Amiodarone and torsades de pointes in patients with advanced heart failure.
Amiodarone is considered to be safe in patients with prior QT prolongation and torsades de pointes taking class I antiarrhythmic agents who require continued antiarrhythmic drug therapy. However, the safety of amiodarone in advanced heart failure patients with a history of drug-induced torsades de pointes, who may be more susceptible to proarrhythmia, is unknown. Therefore, the objective of this study was to assess amiodarone safety and efficacy in heart failure patients with prior antiarrhythmic drug-induced torsades de pointes. We determined the history of torsades de pointes in 205 patients with heart failure treated with amiodarone, and compared the risk of sudden death in patients with and without such a history. To evaluate the possibility that all patients with a history of torsades de pointes would be at high risk for sudden death regardless of amiodarone treatment, we compared this risk in patients with a history of torsades de pointes who were and were not subsequently treated with amiodarone. Of 205 patients with advanced heart failure, 8 (4%) treated with amiodarone had prior drug-induced torsades de pointes. Despite similar severity of heart failure, the 1-year actuarial sudden death risk was markedly increased in amiodarone patients with than without prior torsades de pointes (55% vs 15%, p = 0.0001). Similarly, the incidence of 1-year sudden death was markedly increased in patients with prior torsades de pointes taking amiodarone compared with such patients who were not subsequently treated with amiodarone (55% vs 0%, p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)


Publication trends and knowledge mapping in 3D printing in orthopaedics.
Three dimensional (3D) printing, also called 'rapid prototyping' and 'additive manufacturing' is considered as a "second industrial revolution." With this rapidly emerging technology, CT or MR images are used for the creation of graspable objects from 3D reconstituted images. Patient-specific anatomical models can be, therefore, manufactured efficiently. These can enhance surgeon's understanding of their patients' patho-anatomy and also help in precise preoperative planning. The 3D printed patient-specific guides can also help in achieving accurate bony cuts, precise implant placement, and nice surgical results. Customized implants, casts, orthoses and prosthetics can be created to match an individual patient's anatomy. The 3D printing of individualized artificial cartilage scaffolds and 3D bioprinting are some other areas of growing interest. We aim to study the publication trends in 3D printing as applied to the field of orthopaedics. A literature search was performed to extract all papers related to 3D printing applications in orthopaedics and allied sciences on the Pubmed, Web of Science and SCOPUS databases. Suitable keywords and boolean operators ("3D Printing" OR "3-dimensional printing" OR "3D printed" OR "additive manufacturing" OR "rapid prototyping") AND (''Orthopaedics" OR "Orthopaedics'') were used, in May 2018. Search was attempted in Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Review of Effectiveness (DARE) databases, using keywords 3d printing orthopaedics. A similar search was repeated in pubmed and SCOPUS to get more specific papers.No limits were set on the period or evidence level, as 3D printing in orthopaedics is relatively new and evidence available is usually limited to low-level studies. Trends in a publication on these topics were analyzed, focussing on publications, type of research (basic science or clinical), type of publication, authors, institution, and country. Some citations received by these papers were also analyzed in SCOPUS and Web of Science. MS Excel (2008 - Mac version) and VOS Viewer1.6.8 (2018- Mac version) software were used to analyze the search results and for citation mapping respectively. We also identified top 10 most cited articles in the field. An increasing trend in publications in 3D printing-related work in orthopedic surgery and related fields was observed in the recent past. A search on Pubmed using the above strategy revealed 389 documents. A similar search revealed 653 documents on SCOPUS, many (314) of which were from an engineering background and only 271 were related to medicine. No papers were found in the Cochrane database. Search on TRIP database revealed 195 papers. A similar search revealed 237 papers on orthopedic applications on Pubmed and 269 documents on SCOPUS, whereas a search on Web of Science revealed only 23 papers. Publication trends were then analyzed on data derived from SCOPUS database. Overall, most papers were published from China, followed by United States, United Kingdom, and India. There has been an upsurge of interest in 3D printing in orthopedic surgery, as is evident by an increasing trend in research and publications in this area in the recent years. Presently, 3D printing is in a primitive stage in the field of orthopedic surgery as our knowledge is still insufficient, and costs and learning curve are somewhat high. However, looking at latest publication trends, we are enthusiastic that it holds the key to future in orthopaedics and trauma cases.


Attempts at preventing further spread of bovine virus diarrhoea virus (BVDV) infection in 5 Danish dairy herds in which BVDV had been isolated.
In 5 herds in which bovine virus diarrhoea virus (BVDV) had been isolated, all animals were bled for virological and serological examination. After the herd blood test, follow up blood tests were made on calves born up to 6 months later in 1 herd, 9 months later in 1 herd and up to 12 months later in 3 herds. Persistently infected animals (PI animals) were removed and after a time period a small herd sample of 10 animals that were born after removal of the PI animals were examined for BVDV antibodies. At the herd blood test a total of 21 PI animals were detected. During the follow up period another 25 PI animals were born. Among animals in the small herd samples collected after removal of the PI animals, antibody positive animals were found in the 2 herds with the shortest follow up period. In the 3 herds with a 1 year follow up period there were no antibody carriers in the herd sample. It seems possible to prevent further spread of infection with BVDV if all animals in the herds as well as animals born during the following year are examined and PI animals removed.


Developing a concept of hope from a human science perspective.
This article explores concept development from a human science perspective and uses concept inventing, a method described by Parse, for developing the concept of hope as inspired by the Taiwanese folk song "Mending a Torn Fish Net." The synthesized definition is hope is resolute picturing of the possibilities amid the restrictions-opportunities of communion-aloneness while creatively metamorphosing. This definition is explicitly connected to the three principles of Parse's theory of human becoming. Reflections on research and practice are provided.


Diagnostic delay in psychogenic nonepileptic seizures.
Delay to diagnosis was studied in 313 consecutive patients with psychogenic nonepileptic seizures (PNES). On average, patients with PNES were diagnosed 7.2 years after manifestation (SD 9.3 years). Younger age, interictal epileptiform potentials in the EEG, and anticonvulsant treatment were associated with longer delays. Other patient factors did not explain the great variability of the time to diagnosis, suggesting that physician factors contributed to delays.


Enhanced levels of asymmetric dimethylarginine in a serum of middle age patients with myelodysplastic syndrome.
Myelodysplastic syndromes (MDS) are hematological malignancies of unclear etiology where oxidative stress may contribute to the pathogenesis. Methylarginines, naturally occurring inhibitors of NO synthase, can increase superoxide generation from uncoupled NO synthase. We found significant increase in concentrations of asymmetric dimethylarginine (0.84 ± 0.32 μmol/L, p = 0.0022) and malondialdehyde (0.77 ± 0.11 μmol/L, p < 0.001) in sera of MDS patients vs controls (asymmetric dimethylarginine: 0.56 ± 0.16 μmol/L, malondialdehyde: 0.52 ± 0.07 μmol/L). On the contrary, nitrites concentrations were significantly decreased in MDS patients (1.71 ± 0.46 μmol/L, p = 0.0028) vs controls (2.16 ± 0.38 μmol/L). We suppose that the oxidative stress in MDS is enhanced due to methylated arginines influence on NO synthase activity impairment.


Outcomes of Sacral Neuromodulation for Overactive Bladder in Octogenarian Females.
Elderly women have a high incidence of refractory overactive bladder. Clinicians and elderly patients may be hesitant to consider sacral neuromodulation. We investigated outcomes of sacral neuromodulation in women 80 years old or older. From 2000 to 2013, 24 octogenarians with overactive bladder underwent stage 1 implantation of the InterStim® sacral neuromodulation device. We defined stage 1 success as 50% or greater improvement in incontinence episodes and/or pads. Those patients underwent placement of an implantable pulse generator. The primary study outcome was the rate of stage 1 success. Secondary outcomes were the complication rate and patient reported improvement/satisfaction. We identified 24 octogenarians with a median age of 85 years (range 80 to 89), of whom 18 (75%) experienced stage 1 success. At a mean 17-month followup (range 1 to 59) success was sustained in 13 patients (72%) and 15 (83%) were medication free. Two patients (12%) experienced complications, including urinary tract infection in 1 and pain at the implantable pulse generator site in 1, which resolved within 1 month. Three patients (17%) underwent lead revision and 2 subsequently regained success. Five of the 10 patients (50%) who returned the PGI-I questionnaire reported that their condition was very much or much improved, 3 felt a little improved and 2 reported no change. The self-reported satisfaction rate was 60%. Octogenarian women treated with sacral neuromodulation had a high rate of stage 1 success with no major complications. Most of them reported improvement and satisfaction at a mean followup of 17 months. Advanced age alone should not preclude consideration of sacral neuromodulation as a treatment option for overactive bladder in the properly selected elderly patient.


Screening and management of major endocrinopathies during pregnancy: an update.
Endocrinopathies during pregnancy constitute a challenging issue, being prevalent and requiring appropriate management to avoid maternal and fetal complications. This review aims to summarize and present major endocrine problems during pregnancy, the appropriate screening, maternal monitoring and management, fetal monitoring, and follow-up. Glucose metabolism, thyroid function, as well as calcium and vitamin D metabolism are the main endocrine domains that should be screened and monitored during pregnancy. Gestational diabetes mellitus (GDM) is the most prevalent endocrine disease during pregnancy, followed by thyroid disorders. Specific recommendations are provided for the optimal clinical care of pregnant women and their offspring for GDM, thyroid disorders, and calcium and vitamin D disorders.


Role of Rac1 in augmented endothelin-1-induced bronchial contraction in airway hyperresponsive mice.
It has recently been exhibited that Rac1 expression is increased in the bronchial tissue of a murine model with repeated antigen-challenged airway hyperresponsiveness (AHR). In the present study, the role of Rac1 in endothelin-1 (ET-1)-induced bronchial contraction and myosin light chain (MLC) phosphorylation was examined in AHR mice. Enhanced reactions in AHR mice were prevented by the Rac1 inhibitor NSC23766. These findings suggest that increased activation of Rac1 might be responsible for the enhancement of the bronchial contraction induced by ET-1 in AHR.


Molecularly imprinted polyaniline-polyvinyl sulphonic acid composite based sensor for para-nitrophenol detection.
We report results of the studies relating to the fabrication and characterization of a conducting polymer based molecularly imprinted para-nitrophenol (PNP) sensor. A water pollutant, para-nitrophenol is electrochemically imprinted with polyvinyl sulphonic acid (PVSA) doped polyaniline onto indium tin oxide (ITO) glass substrate. This PNP imprinted electrode (PNPI-PANI-PVSA/ITO) prepared via chronopotentiometric polymerization and over-oxidation is characterized by Fourier transform infra-red spectroscopy (FT-IR), UV-visible (UV-vis) spectroscopy, contact angle (CA), scanning electron microscopy (SEM), cyclic voltammetry (CV) and differential pulse voltammetry (DPV) studies. The response studies of PNPI-PANI-PVSA/ITO electrode carried out using DPV reveal a lower detection limit of 1×10(-3) mM, improved sensitivity as 1.5×10(-3) A mM(-1) and stability of 45 days. The PNPI-PANI-PVSA/ITO electrode shows good precision with relative standard deviation of 2.1% and good reproducibility with standard deviation of 3.78%.


[Hormonal sensitivity of mammary adenocarcinoma in rats and the capacity of the sulfhydryl groups of this tumor for bindig by various antineoplastic drugs].
A correlation was studied between the hormone-dependence of DMBA induced mammary carcinomas in rats and their in-vitro sensitivity to thiophosphamide, benzo-TEPA, sarcolysin and ederpine according to the responsiveness of SH-groups of tumor tissues. A reliable positive correlation was found between the hormone-dependence of neoplasms and their sensitivity to thiophosphamide: the more rapid was tumor regression after ovariectomy, the higher the precentage of in vitro binding of tissue homogenate sulfhydrile groups by the substance. In terms of other alkylating substances this correlation was found to be unreliable. A conclusion is made that the test of adenocarcinoma sulfhydrile groups binding to thiophosphamide may enable one to judge the hormonal responsiveness of mammary gland neoplasms.


Hydrogels of agarose, and methacrylated gelatin and hyaluronic acid are more supportive for in vitro meniscus regeneration than three dimensional printed polycaprolactone scaffolds.
In this study, porcine fibrochondrocyte-seeded agarose, methacrylated gelatin (GelMA), methacrylated hyaluronic acid (MeHA) and GelMA-MeHA blend hydrogels, and 3D printed PCL scaffolds were tested under dynamic compression for potential meniscal regeneration in vitro. Cell-carrying hydrogels produced higher levels of extracellular matrix (ECM) components after a 35-day incubation than the 3D printed PCL. Cells on GelMA exhibited strong cell adhesion (evidenced with intense paxillin staining) and dendritic cell morphology, and produced an order of magnitude higher level of collagen (p < 0.05) than other materials. On the other hand, cells in agarose exhibited low cell adhesion and round cell morphology, and produced higher levels of glycosaminoglycans (GAGs) (p < 0.05) than other materials. A low level of ECM production and a high level of cell proliferation were observed on the 3D printed PCL. Dynamic compression at 10% strain enhanced GAG production in agarose (p < 0.05), and collagen production in GelMA. These results show that hydrogels have a higher potential for meniscal regeneration than the 3D printed PCL, and depending on the material used, fibrochondrocytes could be directed to proliferate or produce cartilaginous or fibrocartilaginous ECM. Agarose and MeHA could be used for the regeneration of the inner region of meniscus, while GelMA for the outer region.


The routine use of atypical cultures in presumed aseptic revisions is unnecessary.
In presumed aseptic hip and knee revisions, it is common practice to send intraoperative cultures to screen for occult infection. Currently no guidelines exist for the routine use of acid-fast bacillus (AFB) and fungal cultures in this setting. We established (1) the rate of positive fungal and AFB cultures in aseptic hip and knee revision arthroplasties, (2) factors associated with positive fungal and AFB cultures, (3) the likelihood that positive cultures represent true-positive results, and (4) the hospital charges of sending fungal and AFB cultures routinely. We retrospectively evaluated all 1717 presumed aseptic hip and knee revisions performed from January 2006 to November 2011: 1139 patients had at least one intraoperative fungal culture and 1133 patients had at least one intraoperative AFB culture, with 923 and 920, respectively, achieving 1-year followup. The Musculoskeletal Infection Society criteria were used to classify subsequent infections. We attempted to identify risk factors for positive cultures. We observed six (0.5%) patients with positive AFB cultures and 19 (1.7%) with positive fungal cultures. Patients undergoing reimplantation procedures were more likely to have a positive fungal culture. The true-positive rate was 0% and 0.1% for AFB and fungal cultures, respectively. The total hospital charges for these cultures over the time frame of our study were USD 1,315,533. Given the extremely low rate of true-positive AFB and fungal cultures in presumed aseptic revision joint arthroplasty and the charges associated with maintaining these cultures, we believe their routine use is unwarranted. Level III, prognostic study. See the Instructions for Authors for a complete description of evidence.


Evaluation of the use of chemotherapy and other prognostic variables for surgically excised canine thyroid carcinoma with and without metastasis.
This retrospective study compared the efficacy of surgery alone versus surgery in combination with chemotherapy in the treatment of canine thyroid carcinoma; potential prognostic factors were evaluated. Forty-four dogs with biopsy-confirmed thyroid carcinoma met the inclusion criteria. Twenty-eight dogs were treated with surgery alone and 16 with surgery and chemotherapy. The median survival of dogs treated with surgery and chemotherapy was 518 d, which was not statistically different from that of the dogs treated with surgery alone. The number of thyroid lobes removed at surgery was prognostic with respect to survival. Despite an overall metastatic rate of 48%, the addition of chemotherapy to surgical excision did not improve survival; however, this finding may be due to inadequate power to demonstrate a difference.


Mycophenolate mofetil suspension in pediatric renal transplantation: three-year data from the tricontinental trial.
Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adult solid organ transplant recipients, but data in children and adolescents are scarce. This prospective, multicenter, open-labeled, single-arm study investigated the efficacy and safety of an MMF-based immunosuppressive regimen in 100 pediatric renal transplant recipients over a 3-yr period of time. Three age groups were formed (<6 yr, n = 33; 6 to <12 yr, n = 34; 12-18 yr, n = 33). Basic immunosuppression consisted of MMF (600 mg/m(2) b.i.d), cyclosporin A microemulsion and corticosteroids. Seventy-three percent of patients were given anti-lymphocyte antibody induction therapy, of whom 74% received anti-thymocyte globulin. Patient and graft survival 3 yr after transplantation amounted to 98 and 95%, respectively. Twenty-five percent of all patients suffered a biopsy-proven acute rejection episode in the first 6 month post-transplant. Children undergoing induction therapy exhibited a numerically lower rejection rate (21 vs. 37%, p = 0.11). Three years after transplantation, the acute rejection rate added up to 30% (26% with induction therapy vs. 41% without induction therapy, p = 0.21). The number of patients with acute rejection was lowest in the youngest age group (18%), in comparison with 39% in the 6 to <12 yr and 33% in the 12-18 yr age group, respectively. For the entire patient population, the rate of patients who withdrew prematurely because of adverse events was low (12%). The present study shows that MMF therapy in pediatric renal transplant recipients leads to an excellent patient and graft survival 3 yr post-transplant with an acceptable safety profile.


Improved prediction of higher heating value of biomass using an artificial neural network model based on proximate analysis.
As biomass becomes more integrated into our energy feedstocks, the ability to predict its combustion enthalpies from routine data such as carbon, ash, and moisture content enables rapid decisions about utilization. The present work constructs a novel artificial neural network model with a 3-3-1 tangent sigmoid architecture to predict biomasses' higher heating values from only their proximate analyses, requiring minimal specificity as compared to models based on elemental composition. The model presented has a considerably higher correlation coefficient (0.963) and lower root mean square (0.375), mean absolute (0.328), and mean bias errors (0.010) than other models presented in the literature which, at least when applied to the present data set, tend to under-predict the combustion enthalpy.


Critical periods in the visual system: changing views for a model of experience-dependent plasticity.
Visual system circuitry, a canonical model system for the study of experience-dependent development, matures before and following the onset of vision. Sensory experience or deprivation during an early critical period results in substantial plasticity and is a crucial factor in establishing the mature circuitry. In adulthood, plasticity has been thought to be reduced or absent. However, recent studies point to the potential for change in neuronal circuits within the mature brain, raising the possibility that aberrant circuit function can be corrected. In this review, we will discuss recent exciting findings in the field of experience-dependent plasticity that advance our understanding of mechanisms underlying the activation, expression, and closure of critical periods in the visual system.


Detection of transient capacitance increase associated with channel formation in lipid bilayers.
The insertion of alpha- and beta-latrotoxins and sea anemone (Radianthus macrodactilus) toxin into bilayer lipid membranes (BLMs) was investigated using the method of simultaneous conductance/capacitance measurement. All the toxins investigated induced capacitance changes which preceded toxin-induced conductance increases. The processes that may underlie the observed effect are discussed.


Impacts of red mud on lignin depolymerization and humic substance formation mediated by laccase-producing bacterial community during composting.
The aim of this study was to investigate the impacts of red mud on lignin degradation, humic substance formation and laccase-producing bacterial community in composting to better improve composting performances. The results indicated that the organic matter contents of final compost products in the treatment group with red mud (T) decreased by 25.74%, which was more than the control group without red mud (CK) (12.09%). The final lignin degradation ratio and humic substance concentration of the T were 18.67% and 22.80% higher than that of the CK, respectively. The final C/N values of compost in the CK and T were 11.32 and 10.66, respectively, which were both less than 15, suggesting that compost reached maturity. Redundancy analysis showed that temperature was the main factors driving the variation of laccase-producing bacterial community. Pearson analysis suggested that Pseudomonas, Phenylobacterium, and Caulobacter were the most significantly correlated with lignin degradation and humification in the T.


Synchronous small and large bowel cancer developing after pelvic irradiation.
This case report supports the belief that there is a causal relationship between therapeutic radiation and subsequent bowel malignancy.


Classification of l-DOPA pharmacokinetics shapes and creating a predictive model.
It is known that the pharmacokinetics (PK) of levodopa (LD) varies considerably. Difference in PK shapes is expected to affect drug efficacy and development of dyskinesia. In this study, the authors aimed to explore correlations between PK series data of LD and clinical characteristics and dyskinesia in patients with Parkinson's disease (PD). We studied 270 PD patients who underwent PK assessment after administration of LD/carbidopa (100/10 mg) in non-compartmental analysis. The patients were grouped according to similarities in time series data of blood LD concentration. Each group was analyzed with respect to clinical characteristics and PK parameters. We created a model to predict PK patterns based on these findings. PD patients were divided into three groups by clustering analysis: blood LD concentration of the patients in Groups 1 (n = 129), 3 (n = 44) and 2 (n = 97) rose rapidly, relatively slowly and at an intermediate rate, respectively. There were no statistically significant differences in patient characteristics except age among the three groups (one-way ANOVA). Multivariate analysis showed that frequency of dyskinesias in Group 1 was significantly higher than that in Group 2. We successfully created a PK pattern prediction model based on body weight and blood LD concentration at 15 and 30 min after administration. The PK series data of LD was classified into three patterns. The rapid absorption was associated with dyskinesias. Patients' PK patterns were successfully predicted based on their body weight and two-point LD concentration.


Molecular Mechanisms Mediating Involvement of Glial Cells in Brain Plastic Remodeling in Epilepsy.
In this review we summarize published data on the involvement of glial cells in molecular mechanisms underlying brain plastic reorganization in epilepsy. The role of astrocytes as glial elements in pathological plasticity in epilepsy is discussed. Data on the involvement of aquaporin-4 in epileptogenic plastic changes and on participation of microglia and extracellular matrix in dysregulation of synaptic transmission and plastic remodeling in epileptic brain tissue are reviewed.


Dynorphin/KOR inhibits neuronal autophagy by activating mTOR signaling pathway to prevent acute seizure epilepsy.
In previous studies, we found that dynorphin exerts antiepileptic effect by activating the kappa opioid receptor (KOR). However, the role of neuronal autophagy in dynorphin/KOR-mediated antiepileptic is still unclear. This study aimed to investigate the molecular mechanism of dynorphin's antiepileptic effect by inhibiting autophagy and reducing neuronal apoptosis. Here, a pilocarpine-induced rat model of epilepsy was established and hippocampal neurons were treated with Mg2+ -free exposed for epileptiform activity induction. The real-time polymerase chain reaction and Western blot analysis were used to evaluate messenger RNA and protein expression. The TdT-mediated dUTP-biotin nick end labeling staining and flow cytometry were used to analyze cell apoptosis in vivo and in vitro. Neuron cells viability was detected by Cell Counting Kit-8 assay. Immunofluorescent staining and green fluorescent protein-light chain 3 immunofluorescence were used to measure autophagy in vivo and in vitro. Results showed that overexpression of prodynorphin alleviated neuronal apoptosis, activated the mammalian target of rapamycin (mTOR) signaling pathway, and inhibited neuronal autophagy in epileptic rats. Dynorphin inhibited Mg2+ -free-induced seizure-like neuron apoptosis, partially reversing the effect of Mg2+ -free on the mTOR signaling pathway and seizure-like neuron autophagy. Further, using rapamycin, we found that dynorphin inhibited Mg2+ -free-induced seizure-like neuron autophagy and apoptosis by activating the mTOR signaling pathway. In conclusion, dynorphin inhibits autophagy by activating the mTOR signaling pathway and has a protective effect on epilepsy acute seizure and epilepsy-induced brain injury.


Viral proteome size and CD8+ T cell epitope density are correlated: the effect of complexity on selection.
The relation between the complexity of organisms and proteins and their evolution rates has been discussed in the context of multiple generic models. The main robust claim from most such models is the negative relation between complexity and the accumulation rate of mutations. Viruses accumulate escape mutations in their epitopes to avoid detection and destruction of their host cell by CD8+ T cells. The extreme regime of immune escape, namely, strong selection and high mutation rate, provide an opportunity to extend and validate the existing models of relation between complexity and evolution rate as proposed by Fisher and Kimura. Using epitope prediction algorithms to compute the epitopes presented on the most frequent human HLA alleles in over 100 fully sequenced human viruses, and over 900 non-human viruses, we here study the correlation between viruses/proteins complexity (as measured by the number of proteins in the virus and the length of each protein, respectively) and the rate of accumulation of escape mutation. The latter is evaluated by measuring the normalized epitope density of viral proteins. If the virus/protein complexity prevents the accumulation of escape mutations, the epitope density is expected to be positively correlated with both the number of proteins in the virus and the length of proteins. We show that such correlations are indeed observed for most human viruses. For non-human viruses the correlations were much less significant, indicating that the correlation is indeed induced by human HLA molecules.


A computational approach to the inference of sphingolipid pathways from the genome of Aspergillus fumigatus.
A growing body of evidence suggests that sphingolipids are important bioactive molecules, in addition to being critical structural components of cellular membranes. These molecules have been implicated in regulating cell growth, differentiation, angiogenesis, apoptosis, and senescence. Many of the enzymes involved in sphingolipid biosynthesis are the targets of fungal toxins, thus underscoring the importance of this pathway. An international consortium has made considerable progress in sequencing the genome of Aspergillus fumigatus, one of the most common mold pathogens of humans; however, most genes have not yet been annotated. Here, we have identified genes involved in the sphingolipid pathway of A. fumigatus by comparative analysis with four other fungal species and the gene prediction program GlimmerM. Our results shows that A. fumigatus has most of the sphingolipid pathway genes found in other fungi, except for the CSG2 and IPT1 genes; the former is involved in the mannosylation of inositol phosphorylceramide (IPC) to mannose-inositol-phosphorylceramide and the latter involved in the synthesis of mannose-(inositol-P)(2)-ceramide from mannose-inositol-phosphorylceramide.


Family and Cultural Perceptions About Meat Consumption among Hispanic/Latino and White Adults in the United States.
The study examines the extent to which Hispanic/Latino Americans and non-Hispanic White Americans report that meat is an important aspect of their cultural beliefs and practices. An online national survey was completed using quota sampling to recruit approximately equal groups of U.S. Hispanic/Latino and non-Hispanic White Americans (n = 512). A path model predicting willingness to reduce meat consumption was estimated. Hispanic/Latino Americans viewed meat as a more integral aspect of their cultural food practices, and reported that meat dishes comprise a higher percentage of their culture's traditional foods. Cultural beliefs were associated with meat consumption and willingness to reduce meat consumption.


Structural Variations of the Prostatic Urethra Within the Prostate Predict the Severities of Obstructive Symptoms: A Prospective Multicenter Observational Study.
To describe distinctive morphologic variations of the prostate associated with the prostatic urethra, and to determine whether structural changes of the urethra within the prostate resulting from gland enlargement, rather than prostrate volume itself, lead to male lower urinary tract symptom (LUTS). After standardizing measurements, 7 ultrasonography-determined variables, that is, prostate volume, transitional zone volume, transitional zone-to-total volume ratio, presence of intraprostatic protrusion, prostatic urethral angle, prostatic urethral length (PUL), and PUL-to-volume ratio (rPUL), were obtained prospectively in 293 men who had not taken LUTS medication during the 3 months prior to initial visits. Correlations between these variables and international prostate symptom scores (IPSS) were then investigated. By simple correlation, only rPUL showed a significant association with IPSS. Multiple linear regression revealed IPSS were significantly correlated with age (beta = .179, P = .04) and rPUL (beta = .139, P = .019). Subanalysis with respect to the symptoms of IPSS revealed only rPUL was correlated with voiding symptoms (Q1,3,5,6; beta = .122, P = .036), and that age alone was correlated with storage symptoms (Q2,4,7; beta = .262, P < .001). When dividing 4 groups by applying mean cut-offs for PUL (62 mm) and prostate volume (30 g), long PUL with small volume had significantly higher IPSS score than short PUL with large volume (P = .042). Structural differences of prostate related to prostatic urethra as reflected by rPUL were found to be significantly correlated with the severity of voiding symptoms. This finding suggests structural change of the prostatic urethra inducted by prostate enlargement underlies the development of male LUTS.


The Evidence-base for Using Ontologies and Semantic Integration Methodologies to Support Integrated Chronic Disease Management in Primary and Ambulatory Care: Realist Review. Contribution of the IMIA Primary Health Care Informatics WG.
Most chronic diseases are managed in primary and ambulatory care. The chronic care model (CCM) suggests a wide range of community, technological, team and patient factors contribute to effective chronic disease management. Ontologies have the capability to enable formalised linkage of heterogeneous data sources as might be found across the elements of the CCM. To describe the evidence base for using ontologies and other semantic integration methods to support chronic disease management. We reviewed the evidence-base for the use of ontologies and other semantic integration methods within and across the elements of the CCM. We report them using a realist review describing the context in which the mechanism was applied, and any outcome measures. Most evidence was descriptive with an almost complete absence of empirical research and important gaps in the evidence-base. We found some use of ontologies and semantic integration methods for community support of the medical home and for care in the community. Ubiquitous information technology (IT) and other IT tools were deployed to support self-management support, use of shared registries, health behavioural models and knowledge discovery tools to improve delivery system design. Data quality issues restricted the use of clinical data; however there was an increased use of interoperable data and health system integration. Ontologies and semantic integration methods are emergent with limited evidence-base for their implementation. However, they have the potential to integrate the disparate community wide data sources to provide the information necessary for effective chronic disease management.


Newborn Glaucoma: A Neglected Manifestation of Congenital Rubella Syndrome.
To study the frequency of intrauterine rubella infection in a cohort of neonatal-onset glaucoma (NOG) and its effect on the treatment outcomes. Prospective cohort study. Infants with NOG presenting to the pediatric glaucoma service at a tertiary care center in northern India at Chandigarh between January 1, and September 30, 2018, with a minimum postoperative follow-up of 1 year were included in this study. Rubella immunoglobulin-M (IgM) antibodies were tested in all patients. Surgery for intraocular pressure (IOP) control comprised combined trabeculotomy with trabeculectomy or goniotomy. Presenting features and treatment outcomes at 1 year were compared among infants with and without rubella-IgM antibodies. Of 27 eligible infants, 7 (25.9%) were rubella-IgM positive, and all had bilateral glaucoma. One eye in a rubella-positive baby was an unsightly blind eye and required a prosthesis. A total of 13 eyes of 7 patients were compared with 34 eyes of 20 rubella-negative patients. There was no significant difference in mean age and IOP at presentation. Rubella-positive infants had significantly more opaque corneas (P < 0.001), shorter eyes (P < 0.001), and smaller corneal diameters (P = 0.007) at presentation. Two patients in the rubella group had bilateral cataracts, 3 patients had heart disease, and 1 patient had sensorineural deafness. Salt-and-pepper retinopathy was noted in both rubella-positive infants where fundus evaluation was possible. Despite comparable IOP control (P = 0.51), the corneal clarity remained significantly worse in the rubella-positive patients (P = 0.02). Twenty-five percent of those with newborn glaucoma had underlying intrauterine rubella infection, thus making them susceptible for development of congenital rubella syndrome (CRS). Neonatal-onset glaucoma is an important component of CRS, which may present without buphthalmos and persistent corneal clouding despite good IOP control.


Influences of visual and action information on object identification and action production.
To evaluate the impact of semantic information elicited by labels, participants learned to identify or use novel graspable objects associated with novel actions. We identified each object/action pair with labels that elicited visual form or action semantics and varied the congruence between the label's information and the visual form or action of novel objects. In Experiment 1, participants named objects, and in Experiment 2 they produced the action associated with objects. Generally, congruent labels facilitated performance. Furthermore, for participants who learned incongruent associations, the visual form and semantic information elicited by labels influenced performance in opposite patterns. These findings support the notion that naming may be required before actions are produced when object/action associations are novel. Our findings further support the notion that links between the structural properties of objects and their actions may already be stronger than the links between verbal labels and actions in novel object/action associations.


Nationwide experience of cardio- and cerebrovascular complications during infrainguinal endovascular intervention for peripheral arterial disease and acute limb ischaemia.
Endovascular treatment for peripheral arterial disease (PAD) is increasingly used and also continuously applied to more severe vascular pathology. Only few studies report on systemic complications during these procedures, but it is important to address these risks. We report the results of a recent national audit on cardio- and cerebrovascular complications after endovascular procedures for PAD. Data from the Swedish Vascular Registry (Swedvasc) were retrieved on all infrainguinal endovascular procedures performed between May 2008 and December 2011. A total of 9187 cases were analysed regarding the prevalence of myocardial infarction and major stroke within 30 days post-intervention. A literature review in PubMed and Cochrane databases was conducted. The risk of myocardial infarction was 0.3% in intermittent claudication, 1.2% in critical limb ischaemia and 1% in acute limb ischaemia. Corresponding risk of major stroke was 0.4%, 0.3% and 1.4%. Thrombolytic therapy was associated with a threefold risk of major stroke. Only a few studies relevant to the subject were found during the literature review. In this population-based study we found a low risk of cardiac complications, but catheter-administered thrombolytic therapy entailed a non-negligible risk of major stroke.


Oncolytic Virotherapy for Malignant Tumor: Current Clinical Status.
Oncolytic viruses, as novel biological anti-tumor agents, provide anti-tumor therapeutic effects by different mechanisms including directly selective tumor cell lysis and secondary systemic anti-tumor immune responses. Some wide-type and genetically engineered oncolytic viruses have been applied in clinical trials. Among them, T-Vec has a significant therapeutic effect on melanoma patients and received the approval of the US Food and Drug Administration (FDA) as the first oncolytic virus to treat cancer in the US. However, the mechanisms of virus interaction with tumor and immune systems have not been clearly elucidated and there are still no "gold standards" for instructions of virotherapy in clinical trials. This Review collected the recent clinical trials data from 2005 to summarize the basic oncolytic viruses biology, describe the application in recent clinical trials, and discuss the challenges in the application of oncolytic viruses in clinical trials.


Association between serum inflammatory cytokines and disease activity in juvenile idiopathic arthritis.
Circulating interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha), osteocalcin, and conventional parameters of inflammation were examined serially in 14 children with juvenile idiopathic arthritis (JIA) to determine any correlation with the disease activity. Serum IL-1beta was undetectable in all JIA patients. Serum IL-6, white blood cell counts, platelet counts, erythrocyte sedimentation rate and C-reactive protein levels were significantly elevated in the active phase of JIA, whereas hemoglobin levels were significantly lower. Osteocalcin levels were decreased and TNF-alpha increased in active JIA status, but these differences showed no statistical significance. We concluded that inflammatory cytokines play an important role in JIA. Monitoring IL-6 in children with JIA is useful in determining disease activity and response to therapy. These findings confirm earlier reports.


N-phenyl-1-naphthylamine (PNA) Accumulates in Snapping Turtle (Chelydra serpentina) Liver Activating the Detoxification Pathway.
Substituted phenylamine antioxidants (SPAs) are used in Canadian industrial processes. SPAs, specifically N-phenyl-1-naphthylamine (PNA), have received very little attention despite their current use in Canada and their expected aquatic and environmental releases. There is a research gap regarding the effects of PNA in wildlife; therefore, Chelydra serpentina (common snapping turtle) was studied due to its importance as an environmental indicator species. A chronic experiment was performed using PNA spiked food (0 to 3446 ng/g) to determine its toxicity to juvenile C. serpentina. A significant increase in cyp1a mRNA level was observed in the liver of turtles exposed to 3446 ng/g PNA, suggesting that phase I detoxification is activated in the exposed animals. Additionally, a significant decrease in cyp2b transcript level was observed at the two lowest PNA doses, likely indicating another metabolic alteration for PNA. This study helped determine the molecular effects associated with a PNA exposure in reptiles.


Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory.
There are approximately 8.5 million Alzheimer disease (AD) patients who need anesthesia and surgery care every year. The inhalation anesthetic isoflurane, but not desflurane, has been shown to induce caspase activation and apoptosis, which are part of AD neuropathogenesis, through the mitochondria-dependent apoptosis pathway. However, the in vivo relevance, underlying mechanisms, and functional consequences of these findings remain largely to be determined. We therefore set out to assess the effects of isoflurane and desflurane on mitochondrial function, cytotoxicity, learning, and memory using flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry, and the fear conditioning test. Here we show that isoflurane, but not desflurane, induces opening of mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, reduction in levels of mitochondrial membrane potential and adenosine-5'-triphosphate, activation of caspase 3, and impairment of learning and memory in cultured cells, mouse hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3 activation, and impairment of learning and memory. Finally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species. These findings suggest that desflurane could be a safer anesthetic for AD patients as compared to isoflurane, and elucidate the potential mitochondria-associated underlying mechanisms, and therefore have implications for use of anesthetics in AD patients, pending human study confirmation.


The effect of rate of eruption on periodontal ligament glycosylaminoglycan content and enamel formation in the rat incisor.
The rate of eruption of rat mandibular incisors was either increased by cutting one tooth out of occlusion or eliminated by means of pinning. The effects of such changes in eruption rate on the sulphated glycosylaminoglycan content of the periodontal ligaments was analysed. The length of the enamel secretory zone and the composition of the developing enamel matrix protein was also compared. Sulphated glycosylaminoglycan content of the periodontal ligament increased fourfold (P < 0.001) during accelerated eruption but decreased to a corresponding extent (P < 0.001) in the absence of eruption, when compared with controls. The length of the enamel secretory zone was also significantly reduced in the immobilised teeth, although the protein content was similar compared with controls. The results demonstrate the differential response to varied eruption rates of the periodontal ligament and enamel, particularly in respect of the extracellular matrix. The data are consistent with the view that the ground substance of the periodontal ligament plays a role in the generation of the eruptive force.


Lipid Structure Influences the Digestion and Oxidation Behavior of Docosahexaenoic and Eicosapentaenoic Acids in the Simulated Digestion System.
Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential for human health but prone to oxidation. While esterification location is known to influence the stability of omega-3 in triacylglycerols (TAGs) in oxidation trials, their oxidative behavior in the gastrointestinal tract is unknown. Synthesized ABA- and AAB-type TAGs containing DHA and EPA were submitted to static in vitro digestion for the first time. Tridocosahexaenoin and DHA as ethyl esters were similarly digested. Digesta were analyzed by gas chromatography, liquid chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy. Besides the formation of di- and monoacylglycerols, degradation of hydroperoxides was detected in ABA- and AAB-type TAGs, whereas oxygenated species increased in tridocosahexaenoin. Ethyl esters were mainly unaffected. EPA was expectedly less susceptible to oxidation prior to and during the digestion process, particularly in sn-2. These results are relevant for the production of tailored omega-3 structures to be used as supplements or ingredients.


Gait differs between unilateral and bilateral knee osteoarthritis.
To compare walking biomechanics in the most painful leg, and symmetry in biomechanics between legs, in individuals with (1) unilateral pain and structural osteoarthritis (OA), (2) unilateral pain, but bilateral structural OA, and (3) bilateral pain and structural OA and in (4) an asymptomatic control group. Cohort study. Laboratory based. Participants with symptomatic and/or radiographic medial tibiofemoral OA in one or both knees (n=91), and asymptomatic control participants (n=31). Not applicable. The peak knee adduction moment, peak knee flexion moment, knee varus-valgus angle, peak knee flexion angle, toe-out, and trunk lean were computed from 3-dimensional analysis of walking at a self-selected speed. After controlling for walking speed, greater trunk lean toward the more painful knee and reduced flexion in the more painful knee were observed in all OA groups compared with the control group. Between-knee asymmetries indicating greater varus angle and a lower external flexion moment in the painful knee were present in those with unilateral pain and either unilateral or bilateral structural OA. Knee biomechanics were symmetrical in those with bilateral pain and structural OA and in the pain free control group. The presence of pain unilaterally appears to be associated with asymmetries in knee biomechanics. Contrary to this, bilateral pain is associated with symmetry. This suggests that the symptomatic status of both knees should be considered when contemplating unilateral or bilateral biomechanical interventions for medial knee OA.


LncRNA metastasis-associated lung adenocarcinoma transcript-1 promotes osteogenic differentiation of bone marrow stem cells and inhibits osteoclastic differentiation of Mø in osteoporosis via the miR-124-3p/IGF2BP1/Wnt/β-catenin axis.
Osteoporosis is defined as a skeletal disorder characterized by impairment in bone strength. The potential application of lncRNAs as therapeutic targets for osteoporosis has been unveiled. This study investigated the regulatory mechanism of lncRNA MALAT1 in the differentiation of bone marrow stem cells (BMSCs) and macrophages (Mø) in osteoporosis. MALAT1 expression in peripheral blood of elderly osteoporosis patients and healthy volunteers was detected. BMSCs and mononuclear Mø were isolated and cultured. Osteogenic differentiation of BMSCs and osteoclastic differentiation of Mø were induced. BMSCs and Mø were transfected with si-MALAT1, miR-124-3p mimics, miR-124-3p inhibitor, or pcDNA IGF2BP1, followed by detection of cell differentiation. The target microRNAs (miRs) and downstream genes and signaling pathways of MALAT1 were examined. The ovariectomy-induced mouse model of osteoporosis was established, and the mice were injected with pcDNA-MALAT1. MALAT1 was downregulated in osteoporosis patients, increased in BMSCs after osteogenic differentiation, and diminished in Mø after osteoclastic differentiation. Downregulation of MALAT1 repressed osteogenic differentiation of BMSCs and facilitated osteoclastic differentiation of Mø. MALAT1 upregulated IGF2BP1 expression by competitively binding to miR-124-3p. miR-124-3p silencing reversed the effect of si-MALAT1 on BMSCs and Mø differentiation, and IGF2BP1 upregulation averted the effect of overexpressed-miR-124-3p by activating the Wnt/β-catenin pathway. Upregulation of MALAT1 activated the Wnt/β-catenin pathway and attenuated bone injury in mice. In conclusion, lncRNA MALAT1 promoted the osteogenic differentiation of BMSCs and inhibited osteoclastic differentiation of Mø in osteoporosis via the miR-124-3p/IGF2BP1/Wnt/β-catenin axis.


Association Between Operative Approach and Venous Thromboembolism Rate Following Hepatectomy: a Propensity-Matched Analysis.
The use of minimally invasive approaches to hepatectomy has increased in recent years, but the risk of postoperative venous thromboembolism (VTE) is undefined. We aimed to compare VTE rates after open hepatectomy and minimally invasive hepatectomy using an administrative dataset. Patients with primary or metastatic liver tumors were identified in the National Surgical Quality Improvement Program-targeted hepatectomy database (2016-2018). VTE was compared between patients who underwent open or minimally invasive hepatectomy after a propensity score matching of 1:1 for demographics, comorbidities, and operative factors. A total of 6935 patients underwent open hepatectomy and 2237 underwent minimally invasive hepatectomy. After matching, there were 1968 patients per group without differences in demographics, comorbidities, or operative variables. Prior to matching, the VTE rate was higher among patients who underwent open hepatectomy (2.8% vs. 1.1%, p < 0.001), and open hepatectomy was independently associated with VTE (OR = 1.90, p = 0.006). The VTE rate remained higher among open hepatectomy compared to minimally invasive hepatectomy after matching (2.4% vs. 1.1%, p = 0.003). Open hepatectomy was associated with a higher VTE rate in patients undergoing minor (1.9 vs. 1.0%, p = 0.028) and major hepatectomy (5.0 vs. 1.9%, p = 0.045). Patients who undergo an open hepatectomy for malignancy have a higher incidence of postoperative VTE compared to minimally invasive hepatectomy for both minor and major hepatectomy.


Accuracy of transurethral resection of the prostate versus transrectal needle biopsy in the diagnosis of prostatic carcinoma.
Transurethral prostatic resection for obstructive uropathy often yields malignant tissue in a significant number of patients with prostatic carcinoma. A comparison of the diagnostic accuracy of transurethral prostatectomy and transrectal prostatic biopsy in 139 patients who had both procedures demonstrated no significant difference. It is suggested that patients with obstruction and suspected prostatic carcinoma, who are not candidates for curative treatment, should have transurethral prostatectomy to relieve the obstruction and to confirm the diagnosis simultaneously.


Pre-incisional infiltration for pediatric tonsillectomy: a randomized double-blind clinical trial.
Tonsillectomy is frequently associated with post-operative pain of considerable duration. The aim of the current study is to corroborate our previous observational data by conducting a prospective double-blind placebo-controlled randomized clinical trial to determine the potential effect of pre-incision infiltration of local anesthesia on post-operative pain after tonsillectomy. Randomized double-blind controlled clinical trial. Tertiary care facility in Beirut, Lebanon. Ninety patients who underwent tonsillectomy allocated evenly in three groups. Pre-incision infiltration of 1.5 local anesthetic mixture in each tonsil was performed in conjunction with general anesthesia (infiltration, n=30). Pre-incision infiltration of 1.5 ml of 0.9% of normal saline was applied with general anesthesia (placebo, n=30). GA received only general anesthesia. Post-operative pain at rest, eating soft diet, jaw opening at 0, 6, 12, and once daily for the 10-day follow-up period, hemodynamic stability, hospital stay, parent and surgeon satisfaction, ear pain and analgesics consumption were assessed. Hemodynamic stability was maintained during pre, per and post-operation. 93.1% of infiltration group left the hospital the same day compared to 60% in placebo groups and 41.4% in general anesthesia group (p=0.001). Surgeon's satisfaction was significantly higher in infiltration group compared to placebo and general anesthesia groups (p=0.001). Parent's satisfaction was significantly higher in infiltration group (89.65%) compared to general anesthesia group (13.8%) and placebo group (36.7%) (p=0.001). The average pain scores at rest, on jaw opening and when eating soft diet were significantly lower in infiltration group compared to placebo group and general anesthesia group (p<0.05). Analgesic consumption in placebo and general anesthesia groups were significantly higher compared to infiltration group (p<0.05). This modified pre-incision infiltration of anesthetic mixture combined with general anesthesia reduces significantly post-tonsillectomy pain in children and provides a more rapid return to normal activity compared to general anesthesia alone or in combination with a placebo infiltration.


Sperm motility in the fishes of pesticide exposed and from polluted rivers of Gomti and Ganga of north India.
Investigation of lethal dose of gamma-HCH (gamma isomer of hexachlorocyclohexane), DDT (dichlorodiphenyltrichloroethane) and chlorpyrifos on spermatozoa motility after 40 days exposure in catfish, Heteropneustes fossilis was done under laboratory conditions. The sperm motility was done in the fishes captured from unpolluted ponds of Gujartal considering as reference site and polluted rivers Gomti and Ganga of north India at pre-spermiating stage. Results indicate that 1ppm of gamma-HCH, DDT and chlorpyrifos was lethal dose on sperm motility. The motility of spermatozoa decreased in insecticide exposed fish as well as in the fishes of polluted rivers when compared with their respective controls. The sperm motility was highest at 1:2000 (testicular milt: extender) dilution and duration of sperm motility was 90s after post-activation. The duration of motility also declined in the fishes captured from polluted rivers when compared with the same species captured from the reference site. It is concluded that the insecticides decrease the sperm motility and its duration in exposed fish as well as in the captured fishes from polluted rivers causing the decline in fish population of riverine systems due to influence of xenobiotics on the endocrine system.


Neuroendocrine carcinoma of the parotid gland: a report of two cases with ultrastructural and immunohistochemical studies.
Two cases of primary small cell carcinoma of the parotid gland are reported. This rare neoplasm usually presents as a painful or painless mass in the gland. The finding of neurosecretory granules by electron microscopic study, combined with strong immunoreactivity for neuron-specific enolase and chromogranin, confirms the true neuroendocrine origin of the carcinoma. This tumor appears to have a better prognosis than small cell carcinoma of the lung, which it resembles histologically.


Enteral Feeding and Antibiotic Treatment Do Not Influence Increased Coefficient of Variation of Total Fecal Bile Acids in Necrotizing Enterocolitis.
Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants. In animal models, the accumulation of ileal bile acids (BAs) is a crucial component of NEC pathophysiology. Recently, we showed that the coefficient of variation of total fecal BAs (CV-TBA) was elevated in infants who develop NEC compared to matched controls. However, neither the type of enteral nutrition nor antibiotic treatments-parameters that could potentially influence BA levels-were used to match pairs. Thus, we assessed the relationships between exposure to enteral feeding types and antibiotic treatments with NEC status and CV-TBA. Serial fecal samples were collected from 79 infants born with birth weight (BW) ≤1800 gm and estimated gestational age (EGA) ≤32 weeks; eighteen of these infants developed NEC. Total fecal BA levels (TBA) were determined using a commercially available enzyme cycling kit. Relationships between CV-TBA and dichotomous variables (NEC status, demographics, early exposure variables) were assessed by independent samples t-tests. Fisher's exact tests were used to assess relationships between NEC status and categorical variables. High values for CV-TBA levels perfectly predicted NEC status among infants in this study. However, feeding type and antibiotic usage did not drive this relationship. As in previous studies, high values for the CV-TBA levels in the first weeks of life perfectly predicted NEC status among infants. Importantly, feeding type and antibiotic usage-previously identified risk factors for NEC-did not drive this relationship.


In vivo monitoring of gabapentin in rats: a microdialysis study coupled to capillary electrophoresis and laser-induced fluorescence detection.
Gabapentin (GP) is a new anticonvulsant used in refractory epilepsy. Few studies have monitored the drug in vivo. We report the combination of capillary electrophoresis and laser-induced fluorescence detection (CZE-LIFD) with brain microdialysis and plasma ultrafiltration in an attempt to measure GP and offer an alternative technique for pharmacokinetic studies. We found that CZE-LIFD is capable of linearly measuring 10(-7)-10(-9) M GP in a 1 nL volume. It was also demonstrated that it is possible to monitor GP in prefrontal cortex dialysates and plasma in rats. It is concluded that the method permits in vivo monitoring of the drug in pharmacological as well as in clinical studies.


The effect of cycle length on the atrial refractory period.
The effect of cycle length upon refractory period of the atria was measured in 34 patients. The effect of abrupt change in paced cycle length on atrial refractory period was measured by introducing after every eighth paced cycle (CLP) a test cycle (CLT) at an interval which was either 100 ms longer (CLT = CLP + 100 ms) or shorter (CLT = CLP - 100 ms) than the paced cycle. These findings confirm that: (1) atrial refractory periods shorten with decreasing cycle length during steady state pacing; (2) an abrupt change in paced cycle length results in a change in refractory period. This change is similar in direction but smaller in magnitude than the change which occurs in response to steady state pacing; and (3) there is no correlation between intraatrial conduction time and refractoriness.


Antitrust enforcement in the healthcare industry: the expanding scope of state activity.
To describe the landscape of state antitrust activity and review related research and policy issues. In particular, to examine state laws that attempt to immunize mergers among healthcare providers from state and federal antitrust prosecution and consent decrees issued by state attorneys general permitting healthcare providers to merge. State laws attempting to immunize collaborative activities from state and federal antitrust prosecution and consent decrees between state attorneys general and collaborating healthcare providers. State antitrust agencies have been more willing than federal antitrust agencies to approve mergers that are contingent on the fulfillment of specific conditions that require continued oversight. Research is needed to inform policymakers about the consequences of state-approved mergers on market performance.


First-trimester amniotic fluid acetylcholinesterase electrophoresis.
Acetylcholinesterase (AChE) gel electrophoresis was performed on normal amniotic fluids obtained at 4-15 weeks of pregnancy. Until 8 weeks, all the fluids were AChE-positive; the percentage of positive specimens decreased from 9 until 11 weeks and no positive specimen was found after 12 weeks. This method may allow early prenatal diagnosis of neural tube defects after the 12th week.


[Acute blue urticaria following subcutaneous injection of patent blue dye].
Patent blue (PB) is a lymphatic vessel dye commonly used in France for sentinel lymph node detection in breast cancer, and less frequently in melanoma, and which may induce hypersensitivity reactions. We report a case of acute blue urticaria occurring within minutes of PB injection. Ten minutes after PB injection for sentinel lymph node detection during breast cancer surgery, a 49-year-old woman developed generalised acute blue urticaria and eyelid angioedema without bronchospasm or haemodynamic disturbance, but requiring discontinuation of surgery. Skin testing using PB and the anaesthetics given were run 6 weeks after the episode and confirmed PB allergy. PB was formally contra-indicated. Immediate hypersensitivity reactions to PB have been reported for between 0.24 and 2.2% of procedures. Such reactions are on occasion severe, chiefly involving anaphylactic shock. Two mechanisms are probably associated: non-specific histamine release and/or an IgE-mediated mechanism. Skin tests are helpful in confirming the diagnosis of PB allergy. Blue acute urticaria is one of the clinical manifestations of immediate hypersensitivity reactions to patent blue dye. Skin tests must be performed 6 weeks after the reaction in order to confirm the diagnosis and formally contra-indicate this substance.


Inhalation of hypertonic saline as a bronchial challenge in children with mild asthma and normal children.
The response to bronchial challenge with ultrasonically nebulized 4.5% saline was compared to the response to histamine and isocapneic hyperventilation in a group of children with mild asthma and control subjects. Challenge with 4.5% saline was found to have an accuracy of approximately 80%, compared to 90% for histamine and 80% for hyperventilation. The challenge test was well tolerated by all children. Increasing the dose of 4.5% saline delivered to the children by use of a nebulizer with a higher output improved the accuracy of challenge with 4.5% saline to approximately 90%. This finding suggests that the nebulizer output is an important determinant of the accuracy of bronchial challenge with 4.5% saline. Bronchial challenge with 4.5% saline appears to be a promising addition to the tests of bronchial responsiveness in children, but further studies, particularly documenting the reproducibility and the relationship to clinical asthma, are needed before it can replace the current standard tests.


Triple-synergistic MOF-nanozyme for efficient antibacterial treatment.
The abuse of antibiotics makes bacterial infection an increasingly serious global health threat. Reactive oxygen species (ROS) are the ideal alternative antibacterial approach for quick and effective sterilization. Although various antibacterial strategies based on ROS have been developed, many of them are still limited by insufficient antibacterial efficiency. Here, we have developed an acid-enhanced dual-modal antibacterial strategy based on zeolitic imidazolate frameworks-8 (ZIF8) -derived nanozyme. ZIF8, which can release Zn2+, is chosen as the carrier to integrate glucose oxidase (GOx) and gold nanoparticles (Au NPs) which can produce ROS via a cascade catalytic reaction. Thus, the bactericidal capability of ROS and Zn2+ have been integrated. More importantly, gluconic acid, a "by-product" of the catalytic reaction, can generate an acidic environment to promote both the ROS-producing and Zn2+-releasing, enhancing the overall antibacterial performance further. This triple-synergistic strategy exhibits extraordinary bactericidal ability at a low dosage of 4 μg/mL (for S. aureus) and 8 μg/mL (for E. coli), which shows a great potential of MOF-derived nanozyme for efficient bacterial eradication and diverse biomedical applications.


Multi-histidine functionalized material for the specific enrichment of sialylated glycopeptides.
Sialylation, an important form of glycosylation, is involved in many biological processes and plays an important role in the development of diseases. However, due to the low abundance among various glycosylation and lack of efficient enrichment method with high specificity, the study of sialylation remains a challenge. Herein, multi-histidine modified microspheres (MHM) were synthesized to enrich sialylated glycopeptides. It was found that MHM could selectively enrich sialylated glycopeptides from over 100 times of non-sialylated glycopeptides, which indicated MHM possessed good enrichment specificity towards sialylated glycopeptides. Furthermore, MHM were utilized to the large-scale analysis of protein sialylation, and 510 intact glycopeptides were identified with over 94.5% sialylated glycopeptide specificity from 4 μL human serum. The good specificity could be attributed to the synergistic effect by the electrostatic interaction and hydrophilic interaction. Hence, MHM could provide an alternative approach for the analysis of site-specific sialylation at proteome level from complex biological samples.


Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033).
This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F. Healthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2-6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 μg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3. Overall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > -10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI -10.6). In Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series. ClinicalTrials.gov: NCT04384107; EudraCT 2019-003644-68.


Antibodies specific for branched ribonucleic acids.
A chemically synthesized branched tetranucleotide, G3'p5'A [2'p5'G]3'p5'C corresponding to the consensus sequence at the branch point in introns undergoing RNA splicing, was used as a hapten to elicit antibranch antibodies. Binding assays with 32P-labeled hapten and unlabeled structurally related haptens indicated that the antibodies are highly specific for the branch structure and have some specificity for the A2'p5'G sequence at the branch point, but have essentially none for a variety of other 2'p5' or 3'p5' dinucleotides or for the linear trinucleotide G3'p5'A3'p5'C. Purification of these antibodies by binding to A2'p5'G covalently linked to Sepharose followed by covalent attachment of the purified antibodies to protein A-Sepharose has provided an adsorbent that immunospecifically retains branched oligonucleotides as well as branched introns released from RNAs during in vitro splicing.


Porcine aldo-keto reductase 1C subfamily members AKR1C1 and AKR1C4: Substrate specificity, inhibitor sensitivity and activators.
Most members of the aldo-keto reductase (AKR) 1 C subfamily are hydroxysteroid dehydrogenases (HSDs). Similarly to humans, four genes for AKR1C proteins (AKR1C1-AKR1C4) have been identified in the pig, which is a suitable species for biomedical research model of human diseases and optimal organ donor for xenotransplantation. Previous study suggested that, among the porcine AKR1Cs, AKR1C1 and AKR1C4 play important roles in steroid hormone metabolism in the reproductive tissues; however, their biological functions are still unknown. Herein, we report the biochemical properties of the two recombinant enzymes. Kinetic and product analyses of steroid specificity indicated that AKR1C1 is a multi-specific reductase, which acts as 3α-HSD for 3-keto-5β-dihydro-C19/C21-steroids, 3β-HSD for 3-keto-5α-dihydro-C19-steroids including androstenone, 17β-HSD for 17-keto-C19-steroids including estrone, and 20α-HSD for progesterone, showing Km values of 0.5-11 µM. By contrast, AKR1C4 exhibited only 3α-HSD activity for 3-keto groups of 5α/β-dihydro-C19-steroids, 5β-dihydro-C21-steroids and bile acids (Km: 1.0-1.9 µM). AKR1C1 and AKR1C4 also showed broad substrate specificity for nonsteroidal carbonyl compounds including endogenous 4-oxo-2-nonenal, 4-hydroxy-nonenal, acrolein, isocaproaldehyde, farnesal, isatin and methylglyoxal, of which 4-oxo-2-nonenal was reduced with the lowest Km value of 0.9 µM. Moreover, AKR1C1 had the characteristic of reducing aliphatic ketones and all-trans-retinal. The enzymes were inhibited by flavonoids, synthetic estrogens, nonsteroidal anti-inflammatory drugs, triterpenoids and phenolphthalein, whereas only AKR1C4 was activated by bromosulfophthalein. These results suggest that AKR1C1 and AKR1C4 function as 3α/3β/17β/20α-HSD and 3α-HSD, respectively, in metabolism of steroid hormones and a sex pheromone androstenone, both of which also play roles in metabolism of nonsteroidal carbonyl compounds.