Role of nitric oxide in wound repair.
After injury, wound healing is essential for recovery of the integrity of the body. It is a complex, sequential cascade of events. Nitric oxide (NO) is a small radical, formed from the amino acid L-arginine by three distinct isoforms of nitric oxide synthase. The inducible isoform (iNOS) is synthesized in the early phase of wound healing by inflammatory cells, mainly macrophages. However many cells participate in NO synthesis during the proliferative phase after wounding. NO released through iNOS regulates collagen formation, cell proliferation and wound contraction in distinct ways in animal models of wound healing. Although iNOS gene deletion delays, and arginine and NO administration improve healing, the exact mechanisms of action of NO on wound healing parameters are still unknown. The current review summarizes what is known about the role of NO in wound healing and points out path for further research.


Intestinal symptoms and psychological factors jointly affect quality of life of patients with irritable bowel syndrome with diarrhea.
Patients with irritable bowel syndrome (IBS) have significantly reduced quality of life (QOL). Although intestinal and extraintestinal symptoms, as well as comorbid psychological disorders, may reduce the QOL of IBS patients, the primary determinant of QOL in these patients remains unclear. This study aimed to identify the main factors affecting QOL in patients with IBS with diarrhea (IBS-D). Consecutive patients meeting the Rome III Diagnostic Criteria for IBS-D were enrolled in this study. Patients with organic diseases were excluded. The intestinal symptoms, psychological states and QOL of these patients were evaluated using IBS-specific symptom questionnaires, the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), and the Chinese version of the IBS-QOL instrument. Overall scores for intestinal symptoms were calculated by frequency and degree. This study enrolled 227 IBS-D patients, of mean age 44.68 ± 10.81 years. Their mean overall IBS-QOL score was 71.68 ± 18.54, with the lowest score being for food avoidance (53.71 ± 26.92). Overall IBS-QOL score correlated negatively with overall scores of intestinal symptoms and HAMD and HAMA scores (p < 0.001 each). Overall intestinal symptoms scores correlated negatively with HAMD and HAMA scores (p < 0.001 each). Scores of HAMD, HAMA and structural factors (i.e., anxiety/somatization, cognitive disorder, psychomotor retardation, psychic anxiety, and somatic anxiety) were significantly higher in female than in male patients (p < 0.01). Food avoidance and social reaction scores of female patients were significantly lower than those of male patients (p < 0.05 each). The degree of defecation urgency, frequency of passing mucus and psychomotor retardation were independent factors predicting reduced QOL in IBS-D patients. Intestinal symptoms and psychological factors jointly reduce the QOL of IBS-D patients, with gender differences in the impact of both factors on QOL.


Modeling ErbB2-p130Cas interaction to design new potential anticancer agents.
The ErbB2 receptor tyrosine kinase is overexpressed in approximately 15-20% of breast tumors and associated with aggressive disease and poor clinical outcome. p130Cas represents a nodal scaffold protein regulating cell survival, migration and proliferation in normal and pathological contexts. p130Cas overexpression in ErbB2 human breast cancer correlates with poor prognosis and metastasis formation. Recent data indicate that p130Cas association to ErbB2 protects ErbB2 from degradation, thus enhancing tumorigenesis. Therefore, inhibiting p130Cas/ErbB2 interaction might represent a new therapeutic strategy to target breast cancer. Here we demonstrate by performing Molecular Modeling, Molecular Dynamics, dot blot, ELISA and fluorescence quenching experiments, that p130Cas binds directly to ErbB2. Then, by structure-based virtual screening, we identified two potential inhibitors of p130Cas/ErbB2 interaction. Their experimental validation was performed in vitro and in ErbB2-positive breast cancer cellular models. The results highlight that both compounds interfere with p130Cas/ErbB2 binding and significantly affect cell proliferation and sensitivity to Trastuzumab. Overall, this study identifies p130Cas/ErbB2 complex as a potential breast cancer target revealing new therapeutic perspectives for protein-protein interaction (PPI).


Comparison of vaccine efficacy for different antigen delivery systems for infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L.) in a cohabitation challenge model.
Two strains of IPNV made by reverse genetics on the Norwegian Sp strain NVI-015 (GenBank AY379740) backbone encoding the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs were used to prepare inactivated whole virus (IWV), nanoparticle vaccines with whole virus, Escherichia coli subunit encoding truncated VP2-TA and VP2-PT, VP2-TA and VP2-PT fusion antigens with putative translocating domains of Pseudomonas aeruginosa exotoxin, and plasmid DNA encoding segment A of the TA strain. Post challenge survival percentages (PCSP) showed that IWV vaccines conferred highest protection (PCSP=42-53) while nanoparticle, sub-unit recombinant and DNA vaccines fell short of the IWV vaccines in Atlantic salmon (Salmo salar L.) postsmolts challenged with the highly virulent Sp strain NVI-015 (TA strain) of IPNV after 560 degree days post vaccination. Antibody levels induced by these vaccines did not show antigenic differences between the virulent and avirulent motifs for vaccines made with the same antigen dose and delivery system after 8 weeks post vaccination. Our findings show that fish vaccinated with less potent vaccines comprising of nanoparticle, DNA and recombinant vaccines got infected much earlier and yielded to higher infection rates than fish vaccinated with IWV vaccines that were highly potent. Ability of the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs to limit establishment of infection showed equal protection for vaccines made of the same antigen dose and delivery systems. Prevention of tissue damage linked to viral infection was eminent in the more potent vaccines than the less protective ones. Hence, there still remains the challenge of developing highly efficacious vaccines with the ability to eliminate the post challenge carrier state in IPNV vaccinology.


Check-if-apply approach for consumers and utilities to communicate about drinking water aesthetics quality.
Globally, consumers judge their drinking water through its aesthetic qualities because tastes, odors, and appearances are readily detectable by untrained consumers. Consumer feedback is critical to the water industry for efficient resolution of aesthetic water quality issues, although consumer descriptions of taste and odor issues can sometimes be unfocused or confusing. A user-friendly approach can facilitate consumer communications to utilities in the challenging task of describing drinking water taste and odor issues. The purpose of this study was to develop a list of taste and odor descriptors and test a novel "check-if-apply" approach to describe drinking water quality. The final list contained 28 individual and/or groups of descriptors. 75 participants tested water samples impacted by various tastants or odorants: duplicate samples of chloraminated tap water, tap water with heptanal, tap water with 2-methylisoborneol (MIB), tap water with NaCl, bottled water, and bottled water with CuSO4. Participants used a 9-point hedonic scale (1 = 'dislike extremely'; 9 = 'like extremely') to rate overall liking of each sample, and they used the check-if-apply list to describe the taste or odor. Participants also answered a brief questionnaire and used a 5-point scale (1 = 'very difficult'; 5 = 'very easy') to evaluate their experience using the check-if-apply list. Significant differences were observed in acceptability and sensory profile of samples (p-value <0.05). Tap water with MIB had the lowest acceptability mean score (3.43 ± 1.74), while flavorless bottled water had the highest acceptability mean score (6.23 ± 1.47). 'Salty', 'metallic', 'chemical' and 'musty/earthy' were the dominant descriptors for NaCl, CuSO4, heptanal, and MIB, respectively. Most participants (81%) found the check-if-apply list as 'somewhat easy' to 'very easy' to use (mean = 3.44 ± 1.07) and suggested it as a user-friendly lexicon for consumers and utilities to communicate about water quality.


Correlations between levels of mite and cat allergens in settled and airborne dust.
Thirty homes in Rochester, Minn., 20 of which housed cats, were studied to compare cat and mite allergen concentrations in airborne and settled dust. With Air Sentinels in the bedroom and living room for airborne collections, and a Sample Vac for collections from living room carpet and bedroom mattress, immunochemical quantifications of each were made with various radiometric assays with polyclonal and monoclonal antibodies. The most significant correlations were found between airborne mite in the bedroom and living room (p less than 0.001) and airborne mite in the bedroom and dust from the bedroom mattress (p less than 0.001). Most houses had specific epitopes of both Dermatophagoides pteronyssinus and D. farinae, but D. farinae was present in greater amounts. In seven houses we found greater than 10 micrograms of group I mite allergen per gram of settled dust, indicating that some houses in Minnesota have concentrations of mite allergens high enough to cause allergic disease, even in the winter. Clinical interpretation of these data on air levels is hampered by uncertainty as to whether symptoms are more closely related to average steady-state exposure, which we measured, or to brief heavy concentrations. Further epidemiologic studies are needed to define the concentration of mite and cat allergens in the air that are risk factors for allergic disease. The concentration of cat allergen correlated with mite allergen in the air, but not in settled dust, presumably reflecting the fact that both are influenced by ventilation rate.


Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication.
We have discovered that 3,3',5-triiodothyronine (T3) inhibits binding of a PIP-box sequence peptide to proliferating cell nuclear antigen (PCNA) protein by competing for the same binding site, as evidenced by the co-crystal structure of the PCNA-T3 complex at 2.1 Å resolution. Based on this observation, we have designed a novel, non-peptide small molecule PCNA inhibitor, T2 amino alcohol (T2AA), a T3 derivative that lacks thyroid hormone activity. T2AA inhibited interaction of PCNA/PIP-box peptide with an IC(50) of ~1 μm and also PCNA and full-length p21 protein, the tightest PCNA ligand protein known to date. T2AA abolished interaction of PCNA and DNA polymerase δ in cellular chromatin. De novo DNA synthesis was inhibited by T2AA, and the cells were arrested in S-phase. T2AA inhibited growth of cancer cells with induction of early apoptosis. Concurrently, Chk1 and RPA32 in the chromatin are phosphorylated, suggesting that T2AA causes DNA replication stress by stalling DNA replication forks. T2AA significantly inhibited translesion DNA synthesis on a cisplatin-cross-linked template in cells. When cells were treated with a combination of cisplatin and T2AA, a significant increase in phospho(Ser(139))histone H2AX induction and cell growth inhibition was observed.


Comparison of original and biosimilar infliximab (CTP-13) in biologic-naïve patients with Crohn's disease and ulcerative colitis: a retrospective, multicenter real-life study in Spain.
biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naïve, IBD patients in the real life clinical practice. a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naïve patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naïve patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. two hundred and thirty-nine IBD biologic-naïve patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn's disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.


The obese brain: is it a matter of time?
Understanding how obesity rewires the brain, triggers neuroinflammation and neurodegeneration relies on research using animal models. There is, however, a disconnect between the timeline of human obesity and typical preclinical protocols. We emphasize here the need to adopt models of chronic obesity to study the pathophysiology of human obesity.


A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of theranostic agents. [Corrected].
Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ∼87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.


Circulating endothelial progenitor cells.
Angiogenesis research investigates the formation of new blood vessels in wound healing, tumour growth and embryonic development. Circulating, bone marrow-derived endothelial progenitor cells (EPCs) were first described 8 years ago, yet the exact nature of these endothelial precursor cells remains unclear. The contributions of circulating EPCs to angiogenesis in tumours, ischaemic injury and other diseases as well as their usefulness in the repair of wounded hearts and limbs remain under intense investigation.


Prognostic importance of human papillomavirus type 16 DNA in cervical cancer.
Human papillomavirus (HPV) type 16 DNA is frequent in invasive cervical cancers. Among 43 patients with invasive cervical cancer, HPV-16-positive tumors spread to the parametrial and pelvic lymph nodes significantly more often than did HPV-16-negative tumors (P less than 0.05). Demonstration of HPV-16 DNA in invasive cervical cancers may be an additional prognostic factor for this disease.


Normative values for the spine shape parameters using 3D standing analysis from a database of 268 asymptomatic Caucasian and Japanese subjects.
Sagittal balance analysis has gained importance and the measure of the radiographic spinopelvic parameters is now a routine part of many interventions of spine surgery. Indeed, surgical correction of lumbar lordosis must be proportional to the pelvic incidence (PI). The compensatory mechanisms [pelvic retroversion with increased pelvic tilt (PT) and decreased thoracic kyphosis] spontaneously reverse after successful surgery. This study is the first to provide 3D standing spinopelvic reference values from a large database of Caucasian (n = 137) and Japanese (n = 131) asymptomatic subjects. The key spinopelvic parameters [e.g., PI, PT, sacral slope (SS)] were comparable in Japanese and Caucasian populations. Three equations, namely lumbar lordosis based on PI, PT based on PI and SS based on PI, were calculated after linear regression modeling and were comparable in both populations: lumbar lordosis (L1-S1) = 0.54*PI + 27.6, PT = 0.44*PI - 11.4 and SS = 0.54*PI + 11.90. We showed that the key spinopelvic parameters obtained from a large database of healthy subjects were comparable for Causasian and Japanese populations. The normative values provided in this study and the equations obtained after linear regression modeling could help to estimate pre-operatively the lumbar lordosis restoration and could be also used as guidelines for spinopelvic sagittal balance.


What can clients tell us about whether to use motivational interviewing? An analysis of early-session ambivalent language.
Although motivational interviewing (MI) is an effective method for promoting change in problematic alcohol and other drug use, it does not benefit all clients. Clinicians have little empirical guidance on who is likely to benefit from MI and who is not. We hypothesized that differences in clients' spontaneously offered language early in the session would predict their responsiveness to MI during the remainder of the session. The study obtained coding data from 125 counseling sessions from a large randomized controlled trial of clinician training. A cluster analysis created one group of clients whose language reflected ambivalence, and one group whose language reflected readiness to change. We conducted a univariate analysis of variance to compare the mean change in percent change talk across the session between groups. Clients whose language reflected ambivalence early in the session had a greater change in their percent change talk during the remainder of the session, compared to those whose language reflected greater readiness to change (F (1,90) = 63.02, t = 7.94, p < .001). Surprisingly, the group whose language reflected readiness had a decrease in their percent change talk during the remainder of the session (M = -10.9%, SD = 16.3%). Adjusting the results for regression to the mean effects did not eliminate these differences. Clients' language early in the session may offer clinicians some guidance on whether MI is likely to be useful or counterproductive in the treatment of substance use disorder.


A comprehensive SEER registry analysis of elderly patients with classical Hodgkin lymphoma based on treatment era and race.
We conducted a Surveillance, Epidemiology, and End Results Program (SEER-18) registry analysis of classical Hodgkin lymphoma (cHL) patients more than 60 years old and compared outcomes of those diagnosed between 2006 and 2010 (cohort 1) to those identified between 2011 and 2015 (cohort 2) based on treatment era and race. Cohort 1 had a median overall survival (OS) of 4 years and cohort 2 had a median OS of 4.75 years [hazard ratio (HR): 0.92 (0.85-1.00); p = 0.052]. Non-Hispanic blacks (NHBs) had a similar 5-year OS compared to non-Hispanic whites (NHWs) of 48.6% vs. 50.2% (HR: 0.95 [0.79-1.15]; p > 0.99); on the contrary, Hispanics had worse 5-year OS of 41.8% vs. 48.6% (HR: 1.24 [1.09-1.41]; p < 0.001). NHW was the only race that had improvement in 5-year OS in 2011-2015 compared to 2006-2010 (51% vs. 46.5%, p = 0.002). In the multivariable analysis, older age, male gender, stage III-IV, unmarried status, Hispanic race, lack of chemotherapy, and diagnosis in 2006-2010 were associated with worse OS. Lymphoma was the most common cause of death in 60% of patients. In conclusion, elderly cHL patients diagnosed after 2010 had improved OS by nine months that was most prevalent in NHWs, and disparity in OS existed between NHWs and Hispanics throughout the study period.


Estimated insulin sensitivity predicts incident micro- and macrovascular complications in adults with type 1 diabetes over 6 years: the coronary artery calcification in type 1 diabetes study.
Reduced insulin sensitivity (IS) is well documented in type 1 diabetes (T1D) and may contribute to vascular complications. We examined the association of estimated IS (eIS) with incident macro- and microvascular complications in adults with T1D in the prospective CACTI study. Participants (N=652) were 19-56 years old at baseline and re-examined 6.2±0.6years later. Urinary albumin excretion was measured, and categorized as microalbuminuria or greater. Diabetic retinopathy (DR) was based on self-reported history, proliferative DR (PDR) as history of laser eye therapy and coronary artery calcium (CAC) was measured using electron-beam CT. Progression of CAC was defined as a change in the square root transformed CAC volume score of ≥2.5. IS was estimated (eIS) by an equation derived from clamp studies. Predictors of each complication were examined using stepwise logistic regression and subjects with complications at baseline excluded. Age, T1D duration, sex, HbA1c, SBP, LDL-C, and eIS were considered for inclusion. Greater eIS at baseline predicted lower odds of developing albuminuria (OR: 0.67, 95% CI 0.51-0.88), DR (OR 0.79, 0.64-0.97), PDR (OR: 0.76, 0.57-0.99) and CACp (OR: 0.71, 0.60-0.85) in multivariable models. Greater eIS conferred protection from the development of vascular complications over 6-years in T1D.


Stereotactic Radiotherapy after Radical Prostatectomy in Patients with Prostate Cancer in the Adjuvant or Salvage Setting: A Systematic Review.
(1) Background: Prostate cancer is the most common cancer in men and can be treated with radical prostatectomy (RPE) or radiotherapy in the primary setting. Stereotactic radiotherapy (SBRT) has proven to be effective and well tolerated in this setting. However, if SBRT is an equally promising treatment option if applied in the adjuvant or salvage setting after RPE remains unknown. (2) Methods: We searched the PubMed and Embase databases with the following full-text queries in August 2021 for any combination of the terms "SBRT", "prostate", "adjuvant", "postoperative", "salvage", "stereotactic radiotherapy", "prostate bed". There were no limitations regarding publication date or language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. (3) Results: We identified 11 individual studies that were included in this systematic review. Three publications included patients without prior radiotherapy and the remaining eight patients with prior radiotherapy. In all but two publications the radiation target was the macroscopic recurrence. SBRT was overall well tolerated with acceptable rates of acute and late gastrointestinal or genitourinary toxicity. Quality of life was published for two phase I trials with good results. There was a very heterogeneous reporting on biochemical control after SBRT. (4) Conclusions: At this point, ultra-hypofractionated RT using SBRT to the prostate bed remains experimental and its use should be restricted to clinical trials. Given the biological rationale for extreme hypofractionation in patients with prostate cancer and the acceptable toxicity rates that have been reported, further exploration of this field is warranted.


Single-molecular diodes based on opioid derivatives.
We propose an efficient single-molecule rectifier based on a derivative of opioid. Electron transport properties are investigated within the non-equilibrium Green's function formalism combined with density functional theory. The analysis of the current-voltage characteristics indicates obvious diode-like behavior. While heroin presents rectification coefficient R>1, indicating preferential electronic current from electron-donating to electron-withdrawing, 3 and 6-acetylmorphine and morphine exhibit contrary behavior, R<1. Our calculations indicate that the simple inclusion of acetyl groups modulate a range of devices, which varies from simple rectifying to resonant-tunneling diodes. In particular, the rectification rations for heroin diodes show microampere electron current with a maximum of rectification (R=9.1) at very low bias voltage of ∼0.6 V and (R=14.3)∼1.8 V with resistance varying between 0.4 and 1.5 M Ω. Once most of the current single-molecule diodes usually rectifies in nanoampere, are not stable over 1.0 V and present electrical resistance around 10 M. Molecular devices based on opioid derivatives are promising in molecular electronics.


[Characterization and investigation of 16 European priority polycyclic aromatic hydrocarbons in commercial infant formula milk powder in Hangzhou].
A gas chromatography-mass spectrometry(GC-MS) method for the determination of 16 European priority polycyclic aromatic hydrocarbons(16 EUPAHs) in infant formula milk powder was established, and the characterization and investigation of 16 EUPAHs in 70 milk formula powders were carried out in 2020. After hydrolysis, extraction, saponification and solid phase extraction, infant formula milk powder was detected by GC-MS using DB-EUPAH capillary column(20 m×0.18 mm, 0.14 μm)and quantified by internal standard method. The average recoveries ranged from 67.8% to 116.2% and the relative standard deviations ranged from 2.0% to 15.1%(n=6). The limits of quantification and detection of the method were 0.5 and 0.2 μg/kg, respectively. The content of 16 EUPAHs was <0.2-0.48 μg/kg, including PAH4 content in the range of <0.2-0.91 μg/kg, the characterization and investigation of infant formula powder in 16 EUPAHs mainly chrysene, cyclopenta[c, d]pyrene, benz[a]anthracene, benzo[b]fluoranthene, benzo[g, h, i]perylene. The method is simple, accurate and suitable for the determination of 16 EUPAHs in infant formula milk powder. The result showed that the content of 16 EUPAHs in commercially available infant formula milk powder in Hangzhou was low and all of them met the limit requirement of European Union.


Fyn positively regulates the activation of DAP12 and FcRγ-mediated costimulatory signals by RANKL during osteoclastogenesis.
Osteoclasts (OCs) are the only bone-resorbing cells and are critically involved in various bone-associated diseases, including osteoporosis and rheumatoid arthritis. Differentiation of OCs from bone marrow macrophage cells (BMMs) is regulated by RANK and the adaptor protein (DAP12/FcRγ)-mediated costimulatory signals. However, it is unknown how RANKL/RANK signal stimulates phosphorylation of DAP12/FcRγ to initiate the costimulatory signals. As reported here, we found that OC differentiation and acquisition of bone resorption capacity were suppressed in RANKL-stimulated Fyn(-/-) or Fyn-siRNA-transfected BMMs, but could be restored by overexpression of Fyn kinase in Fyn(-/-) BMMs. However, the RANKL-stimulated proliferation of BMMs was unaffected by the absence of Fyn. In addition, RANKL-stimulated Fyn(-/-) BMMs no longer exhibited the optimal induction of typical OC markers such as NFATc1, c-Fos, c-Src, TRAF6, and cathepsin K or costimulatory signals such as the activating phosphorylations of Syk, PLCγ2, and Gab2. These were restored by overexpression of Fyn in Fyn(-/-) BMMs. Immunoprecipitation studies also indicated that the adaptor proteins DAP12/FcRγ and Syk interacted with RANK during RANKL stimulation in BMMs in a Fyn-dependent manner. Phosphorylation of the DAP12/FcRγ and the recruitment of Syk by DAP12/FcRγ were suppressed in Fyn(-/-) BMMs. This is the first demonstration that Fyn relays the initial RANK/RANKL signal to the ITAM-containing adaptors DAP12/FcRγ for OC differentiation.


Inhibition of rat and human prolidases by captopril.
We examined the effects of captopril on prolidase activity of crude homogenates of various tissues in the rat and in the human. It was found that captopril caused significant inhibition of prolidases from liver, kidney, and intestine in both species, whereas it showed minimal inhibitory effect on erythrocyte prolidase. In the rat, Ki for the inhibition of kidney and liver prolidases was in the range of 25-35 microM while, in the human, the value was considerably higher. The nature of inhibition was found to be competitive both in the rat and in the human. Oral administration of captopril (daily dose, 40 mg/kg) for 7 days in the rat resulted in increased urinary excretion of peptide-bound 4-hydroxy-L-proline compared to controls, indicating in vivo inhibition of tissue prolidases by captopril.


A national probability survey of American Medical Association gynecologists and primary care physicians concerning menopause.
This survey intended to clarify physicians' understanding of the issues surrounding women, menopause, alternative medicine, and drug therapy for the treatment of menopause. This study was designed as a national probability sample survey of primary care physicians and gynecologists nationwide. Its focus was to identify major concerns and issues identified by patients about menopause and perceived communication with effectiveness how to communicate with their patients. Physicians were also asked to rate their comfort level in recommending the use of herbal remedies and which herbal remedy they felt comfortable recommending to interested patients. Data indicated that a patient's complaint about menopausal symptoms was the most common factor leading to discussion of menopausal issues with physicians (91%) and that the primary concern to the patient was management of menopausal symptoms. Other factors were controversies about hormone replacement therapy, long-term health implications of menopause, and hormone replacement therapy. Eighty percent of the physician found confusing messages with regard to menopause to be the most challenging aspect in patient communication. The second most challenging issue is "inconclusive data about hormone replacement therapy" (56%). Seventy-six percent of the physicians found "showing sympathy" to be the most important factor for the physicians to communicate effectively with patients, whereas "being honest and open" was the most important patient attitude cited for the same purpose. When it comes to herbal therapy for menopause symptom control, only 4% of the physicians indicated that none of their patients take any remedies. Only 18% were not very comfortable in discussing or recommending herbal therapies, whereas the rest ranged from fairly comfortable to completely comfortable. This study has provided data with regard to physician understanding of menopause treatment options and their primary interaction with patients on this issue. More in-depth studies concerning efficacy and/or side effects of each available treatment will be the relevant next step, given the controversies about both hormone replacement therapy and alternative therapies. The relative efficacy, safety, and cost-effectiveness of different treatments should also be put into the context of both clinical diagnosis and physicians' clinical judgment. Attention to comments by physicians and patients with regard to communication may produce better information exchange and trust between patient and physician.


Review on the status of goat production, marketing, challenges and opportunities in Namibia.
This paper presents the current status of goat production and marketing in Namibia and its challenges and opportunities. Livestock data and reports from the Directorate of Veterinary Services, Meat Board of Namibia and Namibia Statistics Agency were analysed to establish the current status in goat production and marketing. Namibia has 1.9 million goats of which 54% of the total number is found in the northern communal areas. In the commercial farming sector, Boer goat is the main established breed for meat production, while in northern communal areas, the local indigenous goats are common. Goats are reared under an extensive production system and fully dependent on rangelands. Marketing of goats in the formal market is regulated by the board of the red meat industry, whereas there is no regulated marketing in the informal market. The main purpose of goats farming in communal areas is rather for home consumption; thus, trading becomes secondary when a need for emergency income arises. In the commercial sector, goats are mainly marketed on hoof to the lucrative South African market. The major challenges for goat production are recurrent drought, diseases and parasites, predators and theft and poor management. Organized marketing in communal areas and lack of marketing infrastructure are impeded by small flock sizes that limit the numbers that can be marketed. Consumers' health consciousness provides an opportunity to increase goat production through increased demand for goat meat and milk. Market incentives such as attractive prices, market infrastructure, value addition and support policies for local farmers are imperative to improve goat production and marketing.


Preoperative detection of posterior capsule tear with ultrasound biomicroscopy in traumatic cataract.
We report ultrasound biomicroscopy (UBM) evaluation of a paintball-related traumatic cataract with a posterior capsule tear. Slitlamp examination revealed anterior and posterior subcapsular cataracts with a suspicious tiny posterior capsule tear within the larger area of posterior bulging. Ultrasound biomicroscopy (35 MHz) confirmed the presence of a sub-1.0 mm posterior capsule tear, which was clearly observed intraoperatively and postoperatively. This is the first report illustrating the high performance of 35 MHz UBM in detecting a sub-1.0 mm posterior capsule tear. No author has a financial or proprietary interest in any material or method mentioned.


The Greek version of the Australian Pelvic Floor Questionnaire: Cross-cultural adaptation and validation amongst women with urinary incontinence.
As in Greek settings there is a need to develop validated patient-reported outcomes (PROs) for pelvic floor dysfunction, this study's aim was to cross-culturally adapt and validate the Australian Pelvic Floor Questionnaire (APFQ) into Greek, a 42-item PRO for routine urogynaecological evaluation of four domains; bladder, bowel, prolapse and sexual function. Cross-cultural translation was completed through official multistage forward and back-translation process. Validation involved administering the adapted APFQ (APFQ_GR) to women visiting Greek community-based healthcare settings. International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) was also administered. Comparison between women with and without pelvic floor dysfunction (symptomatic versus control) was also undertaken for exploring discriminatory validity. Test-retest reliability was explored by re-administering APFQ_GR 10-15 days following initial testing and internal consistency was explored against each domain separately as well as total items' score. Greek APFQ translation was successfully performed and piloted to a women sample with varying levels of education for comprehensibility, thus, satisfying the questionnaire's face validity. 100 women (53.7 ± 13.1 years-old) participated in validation, 63 of which predominantly complained of urinary incontinence (UI) and 37 were asymptomatic. There were no ceiling effects. Floor effects were detected for women without symptoms. Moderate to very strong correlations were yielded between APFQ_GR total score and bladder domain, respectively, with ICIQ-UI SF single-item and total score (ρ = 0.403-0.758, p < 0.001), indicating satisfactory criterion-related validity. Moderate correlations were yielded for the sexual function domain with APFQ_GR total score and weaker correlations were found in the other two domains. Independent samples t-test yielded significant differences across the questionnaire's scores (p < 0.001), indicating good discriminatory validity between symptomatic and asymptomatic women. Test-retest reliability was excellent (ICC3,1 = ≥0.998). Internal consistency was very good for each domain and total items' score (Cronbach's α = 0.714-0.924). The Greek APFQ was proven appropriate, comprehensible, valid and reliable for women with urinary incontinence and can thus, be used across Greek healthcare settings. Prolapse and bowel domains merit further research.


Improved 3D-QSAR Prediction by Multiple Conformational Alignments and Molecular Docking Studies to Design and Discover HIV-I Protease Inhibitors.
Inhibition of HIV-I protease enzyme is a strategic step for providing better treatment in retrovirus infections, which avoids resistance and possesses less toxicity. In the course of our research to discover new and potent protease inhibitors, 3D-QSAR (CoMFA and CoMSIA) models were generated using 3 different alignment techniques, including multifit alignment, docking based and Distill based alignment for 63 compounds. Novel molecules were designed from the output of this study. A total of 3 alignment methods were used to generate CoMFA and CoMSIA models. A Distill based alignment method was considered a better method according to different validation parameters. A 3D-QSAR model was generated and contour maps were discussed. The biological activity of designed molecules was predicted using the generated QSAR model to validate QSAR. The newly designed molecules were docked to predict binding affinity. In CoMFA, leave one out cross-validated coefficient (q2), conventional coefficient (r2) and predicted correlation coefficient (r2Predicted) values were found to be 0.721, 0.991 and 0.780, respectively. The best obtained CoMSIA model also showed significant cross-validated coefficient (q2), conventional coefficient (r2) and predicted correlation coefficient (r2Predicted) values of 0.714, 0.987 and 0.721, respectively. Steric and electrostatic contour maps generated from CoMFA and hydrophobic and hydrogen bond donor and hydrogen bond acceptor contour maps from CoMSIA models were used to design new and bioactive protease inhibitors by incorporating bioisosterism and knowledge-based structure-activity relationship. The results from both these approaches, ligand-based drug design and structure-based drug design, are adequate and promising to discover protease inhibitors.


Expression and localization of X11 family proteins in neurons.
The X11/Mint family of proteins comprises X11/X11α/Mint1, X11L/X11β/Mint2, and X11L2/X11γ/Mint3. Each of these molecules is an adaptor protein that contains a phosphotyrosine interaction/binding (PI/PTB) and two PDZ domains in its carboxy-terminal region. X11/Mint family members associate with a broad spectrum of membrane proteins, including Alzheimer's β-amyloid precursor protein (APP), alcadeins, and low density lipoprotein receptor proteins, as well as various cytoplasmic proteins including Arf, kalirin-7, and Munc18. In particular, X11 and X11L are thought to play various roles in the regulation of neural functions in brain. Nevertheless, the protein levels and respective localization of individual family members remain controversial. We analyzed the protein levels of X11 and X11L in the corresponding single- and double-knockout mice. X11 and X11L did not exhibit obvious changes of their protein levels when the other was absent, especially in cerebrum in which they were widely co-expressed. In cerebellum, X11 and X11L localized in characteristic patterns in various types of neurons, and X11 protein level increased without an obvious ectopic localization in X11L-knockout mice. Interestingly, only X11L protein existed specifically in brain, whereas, contrary to the accepted view, X11 protein was detected at the highest levels in brain but was also strongly detected in pancreas, testis, and paranephros. Together, our results indicate that both X11 and X11L exert largely in brain neurons, but X11 may also function in peripheral tissues.


Production of metallothionein polyclonal antibodies using chickens as model.
The production of polyclonal antibodies (pAbs) against metallothioneins (MT) has been done in mammals. In this work, we describe a model where pAbs against rat liver MT were produced in chickens. Liver MT-1 and MT-2 isoforms isolated from rats were used as immunogens. MT was purified by exclusion chromatography and MT isoforms isolated by ionic exchange chromatography. Chickens were immunized with each isoform emulsified with Freund adjuvant over 6 weeks. MT-pAbs obtained from egg yolk were purified by ammonium sulfate precipitation followed by thiophilic interaction chromatography. MT-pAbs were characterized by ELISA, SDS-PAGE electrophoresis, and Western blot assays. Results showed significant titers (1:1,000) of MT-1 and MT-2 IgY in the eggs collected 30 days after the first immunization as determined by a direct ELISA assay; results also show a cross-reaction between MT-1 and MT-2 isoforms: however, the Abs obtained did not react with other non-MT proteins in hepatic homogenates. Sensitivity assays showed that MT-pAbs detected MT-1 and MT-2 at nanogram levels. These data suggest that chickens are an alternative model for producing pAbs against mammal high-homology proteins such as MT.


Variability in accuracy of prostate cancer segmentation among radiologists, urologists, and scientists.
There is increasing research in using segmentation of prostate cancer to create a digital 3D model from magnetic resonance imaging (MRI) scans for purposes of education or surgical planning. However, the variation in segmentation of prostate cancer among users and potential inaccuracy has not been studied. Four consultant radiologists, four consultant urologists, four urology trainees, and four nonclinician segmentation scientists were asked to segment a single slice of a lateral T3 prostate tumor on MRI ("Prostate 1"), an anterior zone prostate tumor MRI ("Prostate 2"), and a kidney tumor computed tomography (CT) scan ("Kidney"). Time taken and self-rated subjective accuracy out of a maximum score of 10 were recorded. Root mean square error, Dice coefficient, Matthews correlation coefficient, Jaccard index, specificity, and sensitivity were calculated using the radiologists as the ground truth. There was high variance among the radiologists in segmentation of Prostate 1 and 2 tumors with mean Dice coefficients of 0.81 and 0.58, respectively, compared to 0.96 for the kidney tumor. Urologists and urology trainees had similar accuracy, while nonclinicians had the lowest accuracy scores for Prostate 1 and 2 tumors (0.60 and 0.47) but similar for kidney tumor (0.95). Mean sensitivity in Prostate 1 (0.63) and Prostate 2 (0.61) was lower than specificity (0.92 and 0.93) suggesting under-segmentation of tumors in the non-radiologist groups. Participants spent less time on the kidney tumor segmentation and self-rated accuracy was higher than both prostate tumors. Segmentation of prostate cancers is more difficult than other anatomy such as kidney tumors. Less experienced participants appear to under-segment models and underestimate the size of prostate tumors. Segmentation of prostate cancer is highly variable even among radiologists, and 3D modeling for clinical use must be performed with caution. Further work to develop a methodology to maximize segmentation accuracy is needed.


Preoperative therapy and long-term survival in gastric cancer: One size does not fit all.
The administration of perioperative chemotherapy represents the Western standard of care for patients with locally advanced gastric cancer. The aim of this study is to determine if the administration of the preoperative component of the perioperative regimen is beneficial in the entire population of patients with locally advanced gastric cancer. Seventy patients undergoing preoperative therapy were compared with 347 patients undergoing upfront gastrectomy. Survival analyses were conducted with Kaplan-Meier curves and Cox regression. Patients undergoing preoperative therapy or undergoing upfront gastrectomy were matched 1:1 using the propensity score matching (PSM) method, and a survival analysis was conducted on matched patients. A subgroup analysis was conducted by tumor location and Lauren histotype. In patients undergoing preoperative therapy, factors significantly associated with survival were T and N downstaging, type of gastrectomy, resection status and Lauren histotype. Preoperative therapy was not significantly associated with survival (p = 0,761 before PSM and p = 0,519 after PSM). After PSM, the independent variables significantly associated with survival were type of gastrectomy, type of lymphadenectomy, R status and postoperative therapy. In the subgroup analysis, preoperative therapy demonstrated a selective association with the location of the tumor (p = 0,055) and with Lauren intestinal histotype (p = 0,002). Preoperative therapy had a non-significant impact on survival in the entire population of gastric cancer patients. The advantage of preoperative therapy seems to be limited to patients with proximal tumors and an intestinal histology. Future studies should better evaluate the diverse response of the different phenotypes of gastric cancer to preoperative therapy.


COVID-19 Infection in Kidney Transplant Recipients: A Single Center Experience.
Kidney transplant recipients appear to be particularly high risk for critical COVID-19 illness owing to chronic immunosuppression and coexisting conditions. The aim of this study is to present the clinical characteristics and outcomes of our hospital's kidney transplant recipients who were hospitalized due to COVID-19 infection. In our retrospective observational study of COVID-19 PCR-positive patients, 31 of them were hospitalized with COVID-19 pneumonia and they were evaluated using demographics, laboratory data, treatment, and outcome. The prognostic nutritional index (PNI), which is calculated using the serum albumin concentration and total lymphocytic count, was also evaluated. The baseline immunosuppressive therapy of patients at the time of admission and the treatments they received during their hospitalization were recorded. All patients were treated with favipiravir. Of the 31 renal transplant patients with COVID-19 pneumonia, 20 were male and the mean age was 52.7 ± 13.4. Nine (29%) of the patients died. All patients were treated with favipiravir for 5 days; laboratory tests were recorded before and after treatment. The mean PNI of the patients who survived was higher than the patients who died. The 9 patients who died had lower PNI and higher neutrophil-to-lymphocyte ratio (NLR), creatinine, l-lactate dehydrogenase (LDH), ferritin, and C-reactive protein (CRP) levels. Hospitalized kidney transplant recipients with COVID-19 have higher rates of mortality. The PNI exhibited good predictive performance and may be a useful clinical marker that can be used for estimating survival in COVID-19 patients.


Management of Postoperative Facet Cysts: A Report of 3 Cases.
The exact underlying etiology behind synovial facet cysts remains unclear, and optimal surgical management continues to be a challenge. The authors present a series of 3 patients who underwent primary lumbar decompression and developed postoperative facet cysts within 6 months of index surgery requiring operative intervention. No patients had radiographic evidence of instability. Average follow-up after revision surgery was 14 months. We report on the 3 cases with the phenomenon of postoperative facet cysts and present a complication that falls within the spectrum of lumbar decompression surgery with several successful treatment options.


Defensive burying behavior in maudsley reactive (MR/Har) and nonreactive (MNRA/Har) rats.
Based upon differences in open field and conflict behaviors, the MR/Har and MNRA/Har rat strains have been proposed as a genetically-based "animal model" for the study of emotionality and/or anxiety. The present study compared the MR/Har and MNRA/Har rat strains in the Defensive Burying paradigm. Prior to testing, female MR/Har and MNRA/Har rats were placed in a 40 X 30 X 40 cm Plexiglas chamber containing clay bedding material (5 cm deep) for 30 minute periods on each of four consecutive days. On the fifth day, a wire wrapped prod was placed at one end of the chamber. Rats were placed in the chamber singly and a 3 mA shock was delivered upon contact with the prod. Defensive Burying behavior (i.e., the moving of bedding material toward or over the prod) was recorded for each animal for 15 minutes postshock. There was no MR/Har versus MNRA/Har difference in the percent of animals exhibiting Defensive Burying, nor was there a MR/Har versus MNRA/Har difference in the latency to initiation or the duration of this behavior. Thus, these genetically-defined Maudsley rat strains do not appear to differ in all "animal models" for the study of anxiety or fear.


[Bacterial contamination of the atmosphere in the dental surgery during preparation with turbine tools].
The aerosol formed during work with turbine tools has an undesirable impact on the environment of dental surgeries. It may cause atmospheric transmission of infection. Recent qualitative and quantitative evaluation of aerosols assumes theoretical knowledge of physical and chemical properties and transformation of the aerosol system. These findings which influenced the selection of methods of the author's more recent measurements are the subject of the submitted paper.


Metabolic dependencies and vulnerabilities in leukemia.
Leukemia cell proliferation requires up-regulation and rewiring of metabolic pathways to feed anabolic cell growth. Oncogenic drivers directly and indirectly regulate metabolic pathways, and aberrant metabolism is central not only for leukemia proliferation and survival, but also mediates oncogene addiction with significant implications for the development of targeted therapies. This review explores leukemia metabolic circuitries feeding anabolism, redox potential, and energy required for tumor propagation with an emphasis on emerging therapeutic opportunities.


Evidence of Saffold virus circulation in Italy provided through environmental surveillance.
Saffold virus (SAFV) is an emerging human cardiovirus associated with respiratory and gastrointestinal infection, and, more recently, to symptoms related to the endocrine, cardiovascular, and neurological systems. Information about SAFV circulation in Italy is scarce. In order to provide insights into the epidemiology of SAFV in Italy, 141 raw sewage samples collected throughout Italy were tested using broad-range nested RT-PCR primers targeting the 5'-NC region. Seven samples (5·0%) were confirmed as SAFV in samples collected in North, Centre and Southern Italy. Typing was attempted through amplification of the VP1 coding region, using both published and newly designed primers, and one sample was characterized as SAFV-2. SIGNIFICANCE AND IMPACT OF THE STUDY: Prevalence, genetic diversity and geographic distribution of SAFV in Italy is currently unknown. This study represents the first detection of SAFV in sewage samples in Italy, suggesting that it is circulating in the population despite lack of clinical reporting. Whether the virus is associated with asymptomatic cases or with undetected gastroenteritis or respiratory illness is unknown. Further studies are needed to investigate on the occurrence and persistence of SAFV in water environments and its waterborne transmission potential.


Health system stewardship of National Health Ministries in the WHO European region: concepts, functions and assessment framework.
To propose an operational framework for assessing the completeness and consistency of the stewardship function of national health ministries. The authors carried out a purposive and multidisciplinary review of the literature and derived an operational framework through iterative discussions and participatory methods. The results of the literature review were compared to the authors' observations of stewardship in action and key functions were matched with case examples from Europe and North America. The operational framework relates six functions of stewardship with national contexts, values and ultimate goals pursued by health systems: to define the vision for health and strategy to achieve better health; to exert influence across all sectors for better health; to govern the health system in a way that is consistent with prevailing values; to ensure that system design is aligned with health system goals; to better leverage available legal and regulatory instruments; and to compile, disseminate and apply intelligence. Challenges in the implementation of stewardship relate to: limitations to the role of health ministries; and to governance, operational and change implementation issues. The framework proposed seems flexible enough to help assess the health system stewardship function; however it should be further tested in practice.


Rational design of a fluorescent microneedle tattoo for minimally invasive monitoring of lymphatic function.
The monitoring of lymphatic drainage is of great importance, particularly in the context of the early detection and diagnosis of several diseases. Existing methods of imaging and monitoring lymphatic drainage can be costly and require trained personnel, posing problems for at-home or point-of-care monitoring. Recently, an alternative approach has been proposed, consisting of using microneedles to deliver a near-infrared (NIR) fluorescent tattoo to the skin, which can be monitored with traditional laboratory-based fluorescence detectors. In this work, we present further development of this approach, using a specifically designed NIR-fluorescent probe and rational optimization of microneedle properties and the spatial location of the NIR dye within the microneedles. Moreover, we demonstrate that this method is compatible with a custom-made portable fluorescence measurement device and able to discriminate between drainage and lack of drainage in vivo in rats.


Universal admission screening strategy for COVID-19 highlighted the clinical importance of reporting SARS-CoV-2 viral loads.
Previously limited to symptomatic patients, our hospital introduced a universal admission screening strategy for coronavirus disease 2019 on 25 April 2020. All patients were tested by RT-PCR. We observed decreased viral loads linked to increased screening of asymptomatic patients highlighting the fact that viral load values could guide infection control decisions.


The outcomes and prognostic factors of patients who underwent reoperation for persistent/recurrent papillary thyroid carcinoma.
While the most suitable approach for treating persistent/recurrent papillary thyroid carcinoma (PTC) remains controversial, reoperation may be considered an effective method. The efficacy of reoperation in patients with locoregional persistent/recurrent PTC, especially those with unsatisfactory radioactive iodine (RAI) ablation results, is still uncertain. This study aimed to clarify the clinical management strategies for locoregional persistent/recurrent PTC and to explore factors that may affect long-term patient outcomes after reoperation. In total, 124 patients who initially underwent thyroidectomy and variable extents of RAI therapy and finally received reoperation for locoregionally persistent/recurrent PTC were included. The parameters associated with recurrence-free survival (RFS) were analysed using a Cox proportional hazards model. Overall, 124 patients presented with structural disease after initial therapy and underwent secondary surgical resection, of whom 32 patients developed further structural disease during follow-up after reoperation. At the time of reoperation, metastatic lymph nodes with extranodal extension (P = 0.023) and high unstimulated thyroglobulin (unstim-Tg) levels after reoperation (post-reop) (P = 0.001) were independent prognostic factors for RFS. Neither RAI avidity nor the frequency and dose of RAI therapies before reoperation affected RFS. Reoperation is an ideal clinical treatment strategy for structural locoregional persistent/recurrent PTC, and repeated empirical RAI therapies performed prior to reoperation may not contribute to the long-term outcomes of persistent/recurrent PTC patients. Metastatic lymph nodes with extranodal extension and post-reop unstim-Tg > 10.1 ng/mL may predict a poor prognosis.


Urban particle size distributions during two contrasting dust events originating from Taklimakan and Gobi Deserts.
The dust origins of the two events were identified using HYSPLIT trajectory model and MODIS and CALIPSO satellite data to understand the particle size distribution during two contrasting dust events originated from Taklimakan and Gobi deserts. The supermicron particles significantly increased during the dust events. The dust event from Gobi desert affected significantly on the particles larger than 2.5 μm, while that from Taklimakan desert impacted obviously on the particles in 1.0-2.5 μm. It is found that the particle size distributions and their modal parameters such as VMD (volume median diameter) have significant difference for varying dust origins. The dust from Taklimakan desert was finer than that from Gobi desert also probably due to other influencing factors such as mixing between dust and urban emissions. Our findings illustrated the capacity of combining in situ, satellite data and trajectory model to characterize large-scale dust plumes with a variety of aerosol parameters.


Sexual function in adolescents and young adults diagnosed with cancer: A systematic review.
The purpose of this systematic review was to identify, with supporting evidence, the impact of cancer and its treatment on the sexual function of adolescents and young adults. PubMed, CINAHL, and PsycINFO articles were searched for relevant studies published in English. Fifteen studies, 13 quantitative and two qualitative, were included in this review. Results indicated that cancer during the adolescent and young adult period has a significant negative impact on certain domains of sexual function in both men and women. Among adolescent and young adult males, there is evidence that cancer has detrimental effects on erection, ejaculation, and orgasm. Among adolescent and young adult females, cancer is associated with decreased desire, but there appear to be mixed findings with respect to arousal, orgasm, and satisfaction. Directions for future research are discussed. A better understanding of the effects of cancer and its treatment during adolescence and young adulthood on sexual function could increase attention paid to sexual health in oncology settings and lead to improved psychosexual services for this population.


Failure to Attend Urology Appointments: A Retrospective Analysis of a Single Urban Academic Practice.
We sought to examine why patients miss appointments in a large academic urology practice. We conducted a retrospective analysis of 83,983 patient appointments in our faculty urology group between May 1, 2017 and December 1, 2020. Appointment data from 17 providers were included. Data were collected on diagnosis, age, gender, insurance type, nonattendance history, lead time between scheduling and appointment, clinic location and outpatient procedures vs general office visit or telehealth visit. A total of 7,592 (9.0%) appointments were missed. Patients seen for oncologic diagnosis had the lowest missed appointment rate (4.5%), as compared with benign urology (9.6%) and pediatrics (13.0%). Previous nonattendance history within the last year was associated with nonattendance again (OR 2.47, 95% CI 2.29-2.66). Patients with Medicaid had the highest rate of missed appointments (17.2%; OR 2.16, 95% CI 2.02-2.32). Increased lead time between appointments increased the odds of nonattendance (OR 1.018/week, CI 1.016-1.020). Patients undergoing procedures had the lowest nonattendance rate (3.4%), compared with both new (11.4%) and followup (10.5%) visits, while both telephone (2.9%; OR 0.41, 95% CI 0.32-0.53) and video (2.8%; OR 0.37, 95% CI 0.20-0.71) visits had lower rates of nonattendance when compared to in-person visits. We found a nonattendance rate of 9% in our practice. Those patients with oncologic diagnoses and those having procedures or telemedicine visits had the lowest rates. Those who have missed an appointment in the past are at the highest risk nonattendance and should be targeted to improve patient health as well as practice efficiency.


ERAS protocol compliance impact on functional recovery in colorectal surgery.
Compliance to ERAS protocols is a process quality measure that is associated to better outcomes. The main objective of this study is to analyze the association between protocol compliance, surgical stress and functional recovery. The secondary objective is to identify independent factors associated to functional recovery. A prospective observational single-centre study was performed. Patients who had scheduled colorectal surgery within an ERAS program from January 2017 to June 2018 were included. We analysed the relationship between protocol compliance percentage and surgical stress (defined by C reactive protein [CRP] blood levels on postoperative 3rd day), and functional recovery (defined by the proportion of patients who meet the discharge criteria on the 5th PO day or before). Multivariate analysis was performed to asses independent factor associated to functional recovery. 313 were included. For every additional percentage point of compliance to the protocol 3rd day C reactive protein plasmatic level decreases 1,46 mg/dL and increases 7% the probability to meet the discharge criteria (p < 0.001 both). Independent factors associated to functional recovery were ASA III-IV (OR 0.26; 0.14-0.48), surgical CR-POSSUM score (OR 0.68; 0.57-0.83), early mobilization (OR 4.22; 1.43-12.4) and removal of urinary catheter (OR 3.35; 1.79-6.27), p < 0,001 each of them. Better compliance to ERAS protocol in colorectal surgery decreases surgical stress and accelerates functional recovery.


Neurodevelopmental outcomes of very low birth weight infants with neonatal sepsis: systematic review and meta-analysis.
To study the impact of neonatal sepsis on the long-term neurodevelopmental outcome in very low birth weight (VLBW) infants. Systematic review and meta-analysis of observational studies comparing neurodevelopmental outcomes in VLBW infants exposed to culture-proven sepsis in the neonatal period with similar infants without sepsis. Seventeen studies involving 15,331 infants were included in the meta-analysis. Sepsis in VLBW infants was associated with an increased risk of one or more long-term neurodevelopmental impairments (odds ratio (OR) 2.09; 95% confidence interval (CI) 1.65 to 2.65) including cerebral palsy (CP; OR 2.09; 95% CI 1.78 to 2.45). Heterogeneity (I(2)=36.9%; P=0.06) between the studies was significant and related to variations in patient characteristics, causative pathogens and follow-up methods. Sensitivity analyses based on study design, follow-up rate and year of birth were not significantly different from the overall analysis. The meta-analysis suggests that sepsis in VLBW infants is associated with a worse neurodevelopmental outcome including higher incidence of CP.


Comparison of functional and oncological outcomes between uterus-sparing radical cystectomy and standard radical cystectomy in females: A retrospective study.
This study aimed to compare the functional and oncological outcomes of females who underwent uterus-sparing radical cystectomy (USRC) and standard radical cystectomy (SRC). Between February 2009 and December 2020, 90 female patients who underwent radical cystectomy with urinary diversion were included in this study, comprising the USRC and SRC groups. Functional outcomes were assessed in 63 patients who only underwent radical cystectomy with neobladder formation. Questionnaire scores, clean intermittent catheterization (CIC) rate, and urinary continence rate were analyzed. Oncological outcomes were assessed in 86 patients, regardless of the urinary diversion type. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared. CIC rate was significantly lower in the USRC group than in the SRC group (14.7% vs. 48.0%; p=0.005). The continence rate was significantly higher in the USRC group than in the SRC group (85.3% vs. 40.0%; p=0.001). There were no significant differences in OS (p=0.890), CSS (p=0.700), or RFS (p=0.270) between the two groups. In multivariate analysis, uterine preservation did not significantly increase the hazard ratio (HR) of OS (HR, 0.62; 95% CI, 0.18-2.11; p=0.450), CSS (HR, 0.99; 95% CI, 0.22-4.40; p=0.990), or RFS (HR, 0.46; 95% CI, 0.19-1.11; p=0.840). USRC resulted in higher continence rates and lower CIC rates than SRC without negatively affecting oncological outcomes. Hence, with thorough deliberation, USRC should be considered for females undergoing radical cystectomy.


Surgical resection in hepatocellular carcinoma patients with minimal background fibrosis: a strategy in the era of organ shortage.
Surgical therapies for hepatocellular carcinoma (HCC) represent the potentially curative approaches and provide patients the greatest survival advantage. We sought to examine the outcomes of patients with HCC treated with surgical resection, transplantation, and local ablation. The Surveillance, Epidemiology, and End Results database was queried for all patients with nonmetastatic HCC from 2004 to 2007 who underwent local ablation (LA), segmental resection (SR), hemihepatectomy or extended resection (ER), or transplantation (TP). Of 16,209 patients with HCC, 3,989 (24.6 %) met criteria for inclusion and received therapies: 1,550 LA (39 %), 703 SR (18 %), 619 ER (16 %), and 1,117 TP (28 %). AFP was elevated in 69 % (2,026 of 2,921), and fibrosis grade 0-4 was noted in 32 % (368 of 1,156). The 3-year survival by procedure was 34 % (LA), 50 % (SR), 54 % (ER), and 74 % (TP), p = .001. In patients with minimal fibrosis, 1-year survival for patients undergoing resection was similar to TP (85 vs. 92 %, p = .346), but greater than LA (69 %, p = .001). Survival after surgical resection for HCC patients without extensive fibrosis appears to be superior to ablation and non-inferior to transplantation. In an era of organ shortage, transplantation may be better reserved for patients with cirrhosis and/or unresectable disease.


Magnetoresistance in the Spin-Orbit Kondo State of Elemental Bismuth.
Materials with strong spin-orbit coupling, which competes with other particle-particle interactions and external perturbations, offer a promising route to explore novel phases of quantum matter. Using LDA + DMFT we reveal the complex interplay between local, multi-orbital Coulomb and spin-orbit interaction in elemental bismuth. Our theory quantifies the role played by collective dynamical fluctuations in the spin-orbit Kondo state. The correlated electronic structure we derive is promising in the sense that it leads to results that might explain why moderate magnetic fields can generate Dirac valleys and directional-selective magnetoresistance responses within spin-orbit Kondo metals.


Organization of psychosocial factors associated with worry about acquiring SARS-CoV-2 among women undergoing cancer treatment: an empirical network comparison approach.
Pandemic-induced anxiety can have adverse mental and somatic health consequences on cancer patients (CP). This study aimed to (1) explore the intricate relationships between worry related to potential SARS-CoV-2 infection, COVID-19 perception, sociodemographic factors, and the perceived effectiveness of lockdown measures and (2) investigate if these relationships differ between cancer patients and individuals without a history of cancer (IWHC). We conducted a cross-sectional quantitative study in France between December 1 and 14, 2020. Network analysis was employed on a sample of 1889 women, including 282 cancer patients and 1607 noncancer individuals. Our findings indicate that CP were 20% more likely to express worry than IWHC. Anxiety is embedded within a complex network involving sociodemographic, cognitive, and emotional factors. The emotional components related to COVID-19 perception were found to play a crucial role. The networks for both groups were observed to be identical. Our study underscores the heightened vulnerability of cancer patients to pandemic-induced anxiety, emphasizing the crucial role of emotional components related to COVID-19 perception. The observed similarities in the anxiety network between cancer patients and those without a history of cancer suggest that universal approaches might be effective across groups. Utilizing the Causal Attitude Network Model, we propose potential methods for managing and reducing individual anxiety levels.


National survey on postoperative care and treatment circuits in neurosurgery.
The analysis of surgical processes should be a standard of health systems. We describe the circuit of care and postoperative treatment for neurosurgical interventions in the centres of our country. From June to October 2014, a survey dealing with perioperative treatments and postoperative circuits after neurosurgical procedures was sent to the chiefs of Anaesthesiology of 73 Spanish hospitals with neurosurgery and members of the Neuroscience Section of SEDAR. We obtained 45 responses from 30 centres (41.09%). Sixty percent of anaesthesiologists perform preventive locoregional analgesic treatment. Pain intensity is systematically assessed by 78%. Paracetamol, non-steroidal anti-inflammatory and morphine combinations are the most commonly used. A percentage of 51.1 are aware of the incidence of postoperative nausea after craniotomy and 86.7% consider multimodal prophylaxis to be necessary. Dexamethasone is given as antiemetic (88.9%) and/or anti-oedema treatment (68.9%). A percentage of 44.4 of anaesthesiologists routinely administer anticonvulsive prophylaxis in patients with supratentorial tumours (levetiracetam, 88.9%), and 73.3% of anaesthesiologists have postoperative surveillance protocols. The anaesthesiologist (73.3%) decides the patient's destination, which is usually ICU (83.3%) or PACU (50%). Postoperative neurological monitoring varied according to the type of intervention, although strength and sensitivity were explored in between 70-80%. There is great variability in the responses, probably attributable to the absence of guidelines, different structures and hospital equipment, type of surgery and qualified personnel. We need consensual protocols to standardize the treatment and the degree of monitoring needed during the postoperative period.


The role of postoperative adjuvant chemotherapy following curative resection for gastric cancer: a meta-analysis.
To evaluate the effect of adjuvant chemotherapy on survival rates after curative resection of gastric cancer, MEDLINE (1969-2006), EMBASE (1974-2006), bibliographies, and review articles were searched for relevant articles. The meta-analysis was finally based on 15 trials that included 3212 patients. RR for death in the treated group was 0.90 (95% CI, 0.84-0.96) (P = 0.0010). Little or no significant benefits were suggested in subgroup analyses between different population and regimens either. Postoperative adjuvant chemotherapy for gastric cancer confers slightly significant benefits compared to the surgery only group. The prognoses after surgery may differ among various population groups or because of different regimens.


Reflections on 18 months in a remote aboriginal practice.
This article aims to address some issues glossed over by the literature on Aboriginal health. An attempt is made to balance the joys and pitfalls of practising in such a setting. I hope doctors considering working in the bush will find it encouraging and informative.


Distinct Alterations in Central Pain Processing of Visceral and Somatic Pain in Quiescent Ulcerative Colitis Compared to Irritable Bowel Syndrome and Health.
Despite relevance to pain chronicity, disease burden, and treatment, mechanisms of pain perception for different types of acute pain remain incompletely understood in patients with inflammatory bowel disease [IBD]. Building on experimental research across pain modalities, we herein addressed behavioural and neural correlates of visceral versus somatic pain processing in women with quiescent ulcerative colitis [UC] compared to irritable bowel syndrome [IBS] as a patient control group and healthy women [HC]. Thresholds for visceral and somatic pain were assessed with rectal distensions and cutaneous thermal pain, respectively. Using functional magnetic resonance imaging, neural and behavioural responses to individually calibrated and intensity-matched painful stimuli from both modalities were compared. Pain thresholds were comparable across groups, but visceral thresholds correlated with gastrointestinal symptom severity and chronic stress burden exclusively within UC. Upon experience of visceral and somatic pain, both control groups demonstrated enhanced visceral pain-induced neural activation and greater perceived pain intensity, whereas UC patients failed to differentiate between pain modalities at both behavioural and neural levels. When confronted with acute pain from multiple bodily sites, UC patients' responses are distinctly altered. Their failure to prioritise pain arising from the viscera may reflect a lack of adaptive behavioural flexibility, possibly resulting from long-lasting central effects of repeated intestinal inflammatory insults persisting during remission. The role of psychological factors, particularly chronic stress, in visceral sensitivity and disease-specific alterations in the response to acute pain call for dedicated mechanistic research as a basis for tailoring interventions for intestinal and extraintestinal pain symptoms in IBD.


Morin mitigates cadmium-induced testicular impairment by stimulating testosterone secretion and germ cell proliferation in mice.
Cadmium (Cd) is one of the heavy metal pollutants present in the environment due to human intervention. It is well known that Cd causes toxicological effects on various organs, including the testes. Morin hydrate is a plant-derived bioflavonoid with antioxidant, anti-inflammatory, and anti-stress properties. Thus, the question can be raised as to whether Morin has an effect on Cd-intoxication-induced testicular impairment. Therefore, the aim of this study was to investigate the role of Morin on Cd-mediated disruption of testicular activity. Mice were divided into three groups: group 1 served as the control group, group 2 was given Cd (10 mg/kg) orally for 35 days, and group 3 was given Cd and Morin hydrate (100 mg/kg) for 35 days. To validate the in vivo findings, an in vitro study on testicular explants was also performed. The results of the in vivo study showed that Cd-intoxicated mice had testicular disorganization, reduced circulating testosterone levels, decreased sperm density, and elevated oxidative stress and sperm abnormality. The expression of the germ cell proliferation marker, germ cell nuclear acidic protein (GCNA), and adipocytokine visfatin were also downregulated. It was observed that Morin hydrate upregulated testicular visfatin and GCNA expression in Cd-intoxicated mice, along with improvement in circulating testosterone, testicular histology, and sperm parameters. Furthermore, the in vitro study showed that Cd-mediated downregulation of testicular visfatin and GCNA expression, along with the suppressed secretion of testosterone from testicular explants, was normalized by Morin treatment, whereas visfatin expression was not. Overall, these data indicate that environmental cadmium exposure impairs testicular activity through downregulation of visfatin and GCNA expression, and Morin might play a protective role against Cd-induced testicular toxicity.


Sustainable utilization of biomass resources for decentralized energy generation and climate change mitigation: A regional case study in India.
Clean energy transition via utilizing biomass resources has been projected as an important climate change mitigation strategy. A vital characteristic of biomass is its localized nature; therefore, bioenergy utilization should follow decentralized planning. Agrarian countries like India can take benefit of its large agricultural biomass waste pool to produce clean renewable energy. However, prior knowledge of spatio-temporal distribution, competing uses, and biomass characteristics are necessary for successful bioenergy planning. This paper assesses biomass resource and its power generation potential at different agro-climatic zone levels in the state of Rajasthan, India considering crop residue biomass (25 different crop residues from 14 crops) and livestock manure (from cattle, buffalo, and poultry). Uncertainties associated with the availability of biomass and the power generation potential are assessed for each agro-climatic zone under different scenarios. Greenhouse gases (GHGs) emissions from biomass-based power generations are also estimated and compared with biomass-equivalent coal power plants. It is observed that the annual biomass power potential of Rajasthan is 3056 MW (2496 MW from crop residues and 560 MW from livestock manure). Scenario analysis suggests that the potential varies from 2445 to 6045 MW under different biomass availability and power plant operating conditions. Annual GHGs emissions due to biomass power generation is 5053 kt CO2eq. Replacing coal-based power with biomass power would result in annual GHGs savings of 11412 kt CO2eq. The paper also discusses various carriers and barriers viz. logistics, institutional, financial and technical in setting up decentralized bioenergy plants. Outcomes of the present study are expected to assist renewable energy planners in India.


Antioxidant effects of gold nanoparticles on early stage of collagen-induced arthritis in rats.
To determine antioxidant effects of prophylactic treatment with gold nanoparticles (AuNPs) in the early stage of collagen-induced arthritis (CIA). The preventive treatment with 13 nm or 50 nm AuNPs injected intraarticularly (i.a.) was started at the induction day (0) of CIA and finished in the early stage of arthritis at the day 10. At the end of experiment blood indices (erythrocyte sedimentation rate, leukocyte and erythrocyte counts), pro-/antioxidant status of blood serum (the amount of malondialdehyde, catalase and total antioxidant activity), and internal organs' weight as well as the changes in the joint tissues and their microscopic structure were evaluated. Both 13 nm and 50 nm AuNPs showed antioxidant effect by increasing the level of catalase activity in the early stage of experimental arthritis. Preventive treatment with 50 nm more than with 13 nm AuNPs suppressed joint swelling. Histopathological asssesment revealed statistically significant reduction of synovial angiogenesis and erosion formation in the cartilage. Pilot transmission electron microscopy (TEM) analysis showed predominant accumulation of 13 nm in the synovial fibroblast lineage cells. Intraarticular injections of 13 nm or 50 nm AuNPs showed an antioxidant action significantly raising catalase activity without causing negative effects on hematological indices. Prophylactic treatment with 50 nm more than with 13 nm AuNPs suppressed joint swelling, synovial angiogenesis and cartilage erosion in the initial stage of arthritis.


Regulation of lipid peroxidation in the retina under the effect of bright light.
Changes in LPO intensity under the effect of exposure to bright light and the possibility of their correction with antioxidants were studied on rabbits with diabetic retinopathy. It was found that enhanced LPO caused by exposure to bright light in rabbits with diabetic retinopathy can be corrected with antioxidants. Phenosan potassium salt, α-tocopherol, and oxypyridine were more effective than SOD and taurine in preventing MDA accumulation. A complex of natural and synthetic antioxidants was most efficient in correcting LPO under conditions of exposure to bright light.


A multi-criteria approach to investigate spatial distribution, sources, and the potential toxicological effect of polycyclic aromatic hydrocarbons (PAHs) in sediments of urban retention tanks.
Bottom sediments deposited in retention tanks (RTs) located on two urban streams (Oliwski and Strzyza) in the central part of Gdansk (Poland) were analysed for polycyclic aromatic hydrocarbons' (PAHs) content. PAHs were extracted from samples with methylene chloride, then the extracts were subjected to clean-up applying the solid phase extraction (SPE) method. Quantitative and qualitative determination of 16 PAHs was performed with the use of gas chromatography/mass spectrometry technique. A multi-dimensional approach was applied to analyse PAHs' spatial distribution, source, and contamination status. Potential sources of PAHs were verified using isomer ratios supported by a statistical approach. The Σ16PAHs (in mg/kg d.w.) ranged from 1.95 ± 0.64 to 20.4 ± 6.8 for RTs located on the Oliwski Stream and from 0.50 ± 0.17 to 8.6 ± 2.9 for RTs located on the Strzyza Stream. PAHs detected in bottom sediments were mainly composed of 4- and 5-ring compounds. PAH isomer ratios such as Phen/Anth, Flth/Pyr, B(a)A/B(a)A + Chry, Inpy/Inpy + B(ghi)P, Flth/Flth + Pyr, Anth/Anth + Phen, and Flth/Flth + Pyr suggested delivery pathways for biomass, coal, and petroleum combustion. Petrogenic PAHs related to fuel leaks from cars were not detected. Statistical analyses confirmed traffic and heating system sources, while factor analysis (FA) pointed out the abrasion of wasting parts of vehicles. Based on threshold levels presented in sediment quality guidelines (SQGs), in most cases, PAHs were at low levels with occasional negative biological effects on organisms. Only sediments deposited in two RTs located on the Oliwski Stream presented harmful features for sediment-dwelling organisms. The risk assessment performed accordingly to the Σ16PAHs presented a moderate and high risk for biota. This study not only reflects the direct threat related to PAH content in bottom sediments, but also highlights the overall pollution of an area, considered to be a recreational part of the city (Oliwski Stream catchment). The findings of this study highlight the need to launch preventative methods to protect the area against pollution from heating system emission and traffic.


Regulation of prostaglandin E2 synthesis in human amnion by protein kinase C.
A role for protein kinase C (PKC) in mediation of prostaglandin E2 synthesis in human amnion cells has been suggested. We have investigated the specificity of the stimulation of PGE2 synthesis by phorbol esters and employed putative PKC inhibitors to demonstrate the specificity of PKC stimulation. The three phorbol esters, tetradecanoyl phorbol-13-acetate, phorbol-12,13-dibutyrate and phorbol-12,13-didecanoate gave concentration-dependent (10(-10)-10(-7)M) increases in PGE2 synthesis when added to amnion cells in monolayer, however, no effect was seen with the structurally similar phorbols phorbol-12-13-diacetate, 4 alpha phorbol-12-13-didecanoate or phorbol base. The stimulatory effect of TPA (10(-8)M) on amnion PGE2 synthesis could be prevented by coincubation with the putative protein kinase C inhibitors 1-(5-isoquinoline sulphonyl) piperazine, 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine, sphingosine and chlopromazine at concentrations of 10(-6)-10(-4)M. Addition of the transcription inhibitor actinomycin D at 10(-6)-10(-5)M prevented TPA (10(-8)M)-induced PGE2 synthesis. However, paradoxically, a further increase in PGE2 synthesis was seen when 10(-9)-10(-7)M actinomycin D was added together with TPA. The phospholipase A2 inhibitor quinacrine was able to prevent the TPA-induced increase in PGE2 synthesis even in the presence of exogenous arachidonic acid suggesting that phospholipase A2 may be a target for PKC action.


Complete genome analysis reveals secondary metabolite biosynthetic capabilities of Streptomyces sp. R527F isolated from the Arctic Ocean.
Marine Streptomyces are considered as important but poorly investigated resources for natural products. A new strain Streptomyces sp. R527F isolated from the Arctic Ocean was shown to produce multiple macrolide antibiotics and several new compounds. The entire genome was sequenced and analyzed to gain a better understanding of the biosynthetic capabilities for future studies. At least 30 gene clusters were detected scattered throughout the genome, responsible for biosynthesizing up to 11 classes of natural products. The complete genome sequence allows for natural product mining and biosynthesis, as well as serving as a reference for other studies such as genomic evolution and adaptation to cold Arctic sediments.


Manual punch versus power harvesting of osteochondral grafts.
The purpose of the study was to analyze the effect on chondrocyte viability of 2 existing methods of harvesting osteochondral grafts used for articular cartilage resurfacing. Acute animal experiment. Power (P) trephine versus manual (M) punch harvesting was tested; 2.7-mm and 4.5-mm dowels were harvested from 8 femoral trochlea from 4 sheep using the Acufex MosaicPlasty system (Andover, MA). Grafts were harvested perpendicular to the articular surface to a depth of 10 mm under constant saline irrigation. Power trephine grafts (n = 46, 2.7 P; n = 45, 4.5 P) were harvested by coupling the serrated trephine to a standard orthopaedic nitrogen powered drill. Manual punch grafts (n = 41, 2.7 M; n=33, 4.5 M) were harvested by malleting the punch to the required depth, minimizing rocking, and only slightly turning the punch on removal. Five 40-microm-thick fresh cartilage sections oriented perpendicular to the articular surface were obtained from each graft and then stained with Syto 13 and ethidium bromide vital stains, and the proportion of live cells per field and physical damage were compared between groups. Masson's trichrome stain was used on paraffin-embedded histologic sections. Power harvesting was technically more difficult and resulted in more gross and light microscopic damage to the osteochondral grafts. Chondrocyte viability was significantly greater for manual punch versus power harvesting of both graft sizes (P <.005). Chondrocyte viability was greater for 4.5 P versus 2.7 P grafts (P <.005), but no difference was found between the 2.7 M and 4.5 M groups (P =.357). Chondrocyte viability is significantly greater using manual punch versus serrated power trephines when harvesting osteochondral grafts for cartilage resurfacing procedures. Power trephines should not be used for this procedure. This study shows that the original method (power trephine) of harvesting osteochondral grafts results in great loss of chondrocyte viability versus manual punch harvesting and should no longer be used.


Elucidating Patterns in the Occurrence of Threatened Ground-Dwelling Marsupials Using Camera-Traps.
Establishing trends in endangered fauna against management efforts is a key but often challenging enterprise. Camera-traps offer a new and literal window into monitoring many different mammalian species. Getting it right demands seeking baseline information about how often target species interact with these devices, prior to setting a long-term monitoring strategy. We used a camera-trap array to collect detection data on three species of threatened ground-dwelling marsupials in south-eastern mainland Australia. Over a four-year period, occupancy estimates for two species of bandicoot (southern brown bandicoot Isoodon obesulus and long-nosed bandicoot Perameles nasuta) and a single species of rat-kangaroo (long-nosed potoroo Potorous tridatylus) were generated. These estimates were variously robust depending on visitation history, but nevertheless indicated persistence of these rare and otherwise under threat species. Detection probability for each species differed between study areas, type of management and with complexity of ground and shrub vegetation cover. The relationship between detection and vegetation structure dictated that survey effort was only robust where conditions were optimal for a given species. Outside of that further survey effort would be required to have confidence in survey outcome. In the future this would demand a different sampling strategy, be that through lengthening survey time or adding additional camera units at sites.


Backscattered dose perturbation effects at metallic interfaces irradiated by high-energy X- and gamma-ray therapeutic beams.
To analyze backscattered dose enhancements near different metallic interfaces for cobalt-60 ((60)Co) gamma rays and 6- and 18-MV photon beams. Measurements were carried out with a PTW thin-window, parallel-plate ionization chamber and an RDM-1F electrometer. Thin sheets of aluminum, mild steel, copper, cadmium and lead were used as inhomogeneities. The chamber was positioned below the inhomogenities with the gantry maintained under the couch. It can be noticed that the backscatter dose factor (BSDF) reaches the saturation value within few millimeters of all inhomogeneities and the thickness at which the saturation value is reached depends on the atomic number of the inhomogeneity. The amount of backscattered radiation was noticed to be greater with lesser-energy photons ((60)Co) compared to the high erenergy photons. The BSDF varies across the beam when the inhomogeneity is present due to the change in beam quality. The backscattered electrons from lead inhomogeneity have a range in the order of 5-7 mm. Higher atomic number inhomogeneities result in an increase in BSDF, as they have higher scattering cross section for the secondary electrons. The increase in dose was noticed for few millimeters upstream from the metallic inhomogeneity, which suggests that the range of backscattered electrons is very small. Since the factors affecting the BSDF at the interface are energy dependent, it is expected that the variation in BSDF will also be sensitive to the beam energy.


Impact of Pediatric Emergency Care Applied Research Network Rules on Admission, Cranial Computed Tomography and Skull X-ray Rates in a Central European Hospital.
Mild head injury is a common cause of pediatric emergency department visits. Cranial computed tomography (CCT) is the diagnostic standard, although it involves inherent radiation risks. Pediatric Emergency Care Applied Research Network (PECARN) clinical prediction rules were developed to reduce the number of CCT scans. They provide a guideline for CCT use in mild head injuries, based on clinical parameters.Our study aims to evaluate the impact of PECARN rules on hospital admission and CCT rate in children with mild head injury. In this retrospective study, we investigated 729 children with mild head injury presenting in the pediatric emergency department between 2012 and 2016. We compared 2 groups, before and after implementation of PECARN criteria in clinical routine. Of 729 included patients (417 male; 5.6 ± 4.8 years;) 380 were seen prior to implementation of the PECARN rules, compared to 349 patients afterwards. Overall admissions to the ward decreased significantly from 83.9% (n = 319) to 71.3% (n = 249) (P < 0.001), a 31.3% reduction. Calculated from all pediatric admissions, the rate of patients with mild head injury fell from 6.0% to 4.3% (P < 0.001).We recorded a nonsignificant decrease in the CCT rate, from 14.7% to 13.2% (P = 0.555).No readmissions were recorded. Our results show a significant reduction in the rate of hospital admission following implementation of the PECARN rules in our hospital. Already low, the CCT rate did not change after implementation.The PECARN rules appear to be safe because no readmissions were recorded.


Percutaneous nephrostomy vs ureteral stent for hydronephrosis secondary to ureteric calculi: impact on spontaneous stone passage and health-related quality of life-a prospective study.
Ureteral calculi can be associated with urinary drainage blockage, requiring urinary diversion with percutaneous nephrostomy (PCN) or retrograde ureteral stent (RUS). Currently no evidence exists to support the superiority of one method over the other. This study proposes to compare both approaches regarding the probability of spontaneous stone passage (SSP) and its effect on patient's quality of life (QoL). A prospective trial was carried out from July to October of 2017. 50 patients were selected with hydronephrosis secondary to ureteral stones requiring urgent urinary diversion and divided into two groups according to diversion technique: percutaneous nephrostomy (PCN) or retrograde ureteral stent (RUS). The rate of SSP and QoL were evaluated. A PCN group (18 patients) and a RUS group (32 patients) were set. Stone size was higher in PCN (median 92 mm2) than RUS (median 47 mm2) (p = .012). The rate of SSP was 25% in RUS group and 38.9% in PCN. On the univariable analysis no statistical effect was found; however, when adjusted for stone size, location, previous ureteral manipulation and expulsive therapy, PCN showed a significant higher chance of SSP than RUS (OR = 6667). Besides, it was found that 30.2% (n = 13) of stones had an upward displacement associated with retrograde endoscopy. A significant decrease between pre- and post-intervention QoL was found with RUS (p < .001), but not found with PCN (p = .206). Patients in RUS group experienced more urinary symptoms, mostly haematuria (68.7% vs 16.7% in PCN group < .001) and dysuria (78.3% vs 16.7% in PCN group, p < .001). PCN was associated with a higher rate of spontaneous stone passage when adjusted for stone size and location. Moreover, PCN was better tolerated and associated with fewer urinary symptoms when compared with RUS.


Experience with 31 sentinel lymph node biopsies for sarcomas and carcinomas in pediatric patients.
Few data exist regarding techniques, indications, and outcomes for sentinel lymph node biopsy in pediatric patients with sarcomas and carcinomas. A retrospective 10-year review was conducted, with Institutional Review Board waiver, of the pathology, lymphoscintigraphy, and clinical records for all pediatric patients selected to undergo sentinel lymph node biopsy at a major cancer center. Thirty-one sentinel lymph node biopsies were performed in 30 pediatric patients (median age, 12 years; range, 2-21 years). With the administration of technetium 99m sulfur colloid, sentinel lymph nodes were identified preoperatively in 30 of 31 cases, and intraoperatively in the remaining case. Radiotracer alone was used in 13 of 31 cases but was supplemented with isosulfan blue dye in the remaining 18 cases. There were no complications. Positive sentinel lymph nodes occurred in 1 of 9 patients with rhabdomyosarcoma and in 2 of 5 patients with breast cancer, and in both of these diseases the sentinel lymph node results helped guide treatment decisions. No other patients had positive sentinel lymph nodes, and among those with nonrhabdomyosarcoma soft-tissue sarcomas there were no lymph node basin recurrences despite a lack of lymph node basin irradiation or formal lymph node dissection. The median follow-up was 48 months (range, 0-111 months). Sentinel lymph node biopsy for pediatric soft-tissue tumors can be performed safely, and the results can alter treatment decisions both for children with rhabdomyosarcoma and adolescents with breast cancer. In patients with nonrhabdomyosarcoma soft-tissue sarcoma, we observed no positive sentinel lymph nodes and no lymph node basin recurrences; these data should prompt the prospective study of sentinel lymph node biopsy as a modality that might help guide the administration or withholding of regional therapy among pediatric patients with nonrhabdomyosarcoma soft-tissue sarcoma.


Alterations in cerebral blood flow and phosphorylated metabolites in piglets during and after partial ischemia.
Ventilated piglets were studied before, during (15 min), and after (90 min) hemorrhagic hypotension to correlate a 60% reduction in cerebral blood flow with cerebral energy state using radiolabeled microspheres (n = 12) and in vivo 31P nuclear magnetic resonance spectroscopy (n = 11). Cerebral blood flow (ml.min-1.100 g-1) decreased during hypotension (98 +/- 28 to 41 +/- 28, p less than 0.05), increased at 5 min postreperfusion (131 +/- 53, p less than 0.05), and returned to control values by 90 min postreperfusion. Cerebral O2 uptake was reduced during partial ischemia, remained depressed 5 min postreperfusion, and increased to within 20% of control values at 90 min postreperfusion. Relative to control, hypotension was associated with decreased (p less than 0.05) phosphocreatine (62 +/- 11%), phosphocreatine/inorganic phosphate ratio (41 +/- 10%), and nucleoside triphosphate (82 +/- 12%) while inorganic phosphate increased (155 +/- 32%, p less than 0.05). During ischemia intracellular pH dropped from 7.06 +/- 0.07 to 6.59 +/- 0.31 (p less than 0.05) and the cerebral arteriovenous difference of glucose increased. Phosphorylated metabolites returned to within 10% of control 15 min after blood reinfusion and remained constant thereafter. Based on calculations of ATP synthesis and utilization rates during control and hypotension, we speculate that the rate of energy utilization of the brain during ischemia is reduced 18-49% relative to the control utilization rate.


The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy.
Mesenchymal stem cells (MSCs) are ideal for cell-based therapy in various inflammatory diseases because of their immunosuppressive and tissue repair properties. Moreover, their immunosuppressive properties and low immunogenicity contribute to a reduced or weakened immune response elicited by the implantation of allogeneic MSCs compared with other cell types. Therefore, implantation of allogeneic MSCs may be a promising cell-based therapy. In this review, we first summarize the unique advantages of allogeneic MSCs for therapeutic applications. Second, we critically analyze the factors influencing their therapeutic effects, including administration routes, detection time-points, disease models, differentiation of MSCs in vivo, and timing and dosage of MSC administration. Finally, current approaches to allogeneic MSC application are discussed. In conclusion, allogeneic MSCs are a promising option because of their low immunogenicity and immunosuppressive and tissue repair capabilities. Further investigations are needed to enhance the consistency and efficacy of MSCs when used as a cell-based therapy in inflammatory diseases as well as for tissue repair.