Familial multiple endocrine neoplasia type I: the urologist is first on the scene.
To study the urological manifestations of familial multiple endocrine neoplasia type 1 (MEN-1). The study included 26 adults (median age 38.5 years, range 18-80) from two unrelated MEN-1 pedigrees. In 15 of the patients the diagnosis was confirmed by genetic analysis, while in the rest the diagnosis was based on clinical criteria combined with genealogy data. Urolithiasis associated with primary hyperparathyroidism was present in 65% of MEN-1 patients and in 77% of those who were symptomatic. In 68% of patients complications of urolithiasis (renal/ureteric colic, urinary tract infection) were the presenting clinical manifestations of MEN-1, whereas in 50% they constituted the only clinical manifestation of the syndrome. The mean time from the onset of symptoms of urolithiasis to the diagnosis of the polyendocrinopathy was 17.2 years. Initial failure to recognize the presence of MEN-1 in patients with primary hyperparathyroidism led to conservative parathyroid surgery, with subsequent relapse of the hyperparathyroidism, requiring re-operation. Serious renal morbidity included one case of pyonephrosis necessitating nephrectomy. While urolithiasis was a cardinal clinical manifestation of MEN-1, there was otherwise considerable phenotypic polymorphism, even among patients bearing the same MEN1 gene mutation. In patients with familial MEN-1 the complications of urolithiasis are the commonest presenting clinical manifestations and the cause of significant morbidity. In the presence of a family history of renal stones, appropriate investigations may lead to the timely diagnosis of this important, albeit rare, disorder.


Ependymomas: MIB-1 proliferation index and survival.
The biologic behavior of ependymomas is highly variable, and its correlation with histologic features is at best imprecise. This retrospective study attempted to correlate the malignant histologic characteristics of ependymomas with MIB-1 proliferation index and survival. Biopsy and resection specimens taken from 34 patients who received treatment 1972 to 1996 were histologically examined. The patients' ages range was 1 to 59 years. The histologic specimens were assessed for anaplastic features (necrosis, mitosis, vascular proliferation, cellular pleomorphism, and overlapping of nuclei) and an MIB-1 (Ki-67 antigen) proliferation index was also determined. The overall median MIB-1 proliferation index was 7.8% (range 0.1 - 62.5%). An MIB-1 of 20% was significant for a decrease in survival (RR = 5.7) (p = 0.0013). The median MIB-1 for patients < 20 years old was 20.6% with range (0.1, 43%), while that for patients > 20 years was 5.1% (range 0.2, 9.4%) (KW p = 0.055). Three of 5 histological features evaluated were significantly associated with outcome: > 5 mitotic figures per high-power field, necrosis, and vascular proliferation, but not nuclear overlap or pleomorphism. All pathologic factors except pleomorphism were significantly related to the MIB-1 proliferation index. In brief, our data support the association of poor prognoses in ependymomas with young age, the presence of three to four anaplastic histologic features, and an MIB-1 proliferation index > 20%.


Meta-analysis of the quantitative trait loci associated with agronomic traits, fertility restoration, disease resistance, and seed quality traits in pigeonpea (Cajanus cajan L.).
A meta-analysis of quantitative trait loci (QTLs), associated with agronomic traits, fertility restoration, disease resistance, and seed quality traits was conducted for the first time in pigeonpea (Cajanus cajan L.). Data on 498 QTLs was collected from 9 linkage mapping studies (involving 21 biparental populations). Of these 498, 203 QTLs were projected onto "PigeonPea_ConsensusMap_2022," saturated with 10,522 markers, which resulted in the prediction of 34 meta-QTLs (MQTLs). The average confidence interval (CI) of these MQTLs (2.54 cM) was 3.37 times lower than the CI of the initial QTLs (8.56 cM). Of the 34 MQTLs, 12 high-confidence MQTLs with CI (≤5 cM) and a greater number of initial QTLs (≥5) were utilized to extract 2255 gene models, of which 105 were believed to be associated with different traits under study. Furthermore, eight of these MQTLs were observed to overlap with several marker-trait associations or significant SNPs identified in previous genome-wide association studies. Furthermore, synteny and ortho-MQTL analyses among pigeonpea and four related legumes crops, such as chickpea, pea, cowpea, and French bean, led to the identification of 117 orthologous genes from 20 MQTL regions. Markers associated with MQTLs can be employed for MQTL-assisted breeding as well as to improve the prediction accuracy of genomic selection in pigeonpea. Additionally, MQTLs may be subjected to fine mapping, and some of the promising candidate genes may serve as potential targets for positional cloning and functional analysis to elucidate the molecular mechanisms underlying the target traits.


An assessment of some hazards associated with the collection of venous blood.
Some potential hazards of three commercially available blood collecting devices are compared with the conventional syringe method. A simulated venous system using blood containing a bacterial spore tracer was used to estimate surface and aerosol contamination. No appreciable difference in potential hazard to the operator was demonstrable by the methods employed.


The efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer patients of different age groups: a meta-analysis.
Age is closely related to the efficacy of treatment for non-small cell lung cancer (NSCLC) patients. Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in NSCLC patients. However, we had no clear idea of the efficacy of them in elderly patients. So we conducted a meta-analysis to compare the efficacy of immune checkpoint inhibitors for NSCLC patients of different age groups and summarized overall treatment-related adverse events. PubMed, EMBASE, Web of Science and the Cochrane Library were searched for all clinical trials in NSCLC until 30th of April 2019. Eligible studies included randomized controlled trials (RCTs) comparing immune checkpoint inhibitors with chemotherapy in NSCLC patients. The hazard ratio (HRs) and 95% confidence intervals (CIs) of OS, progression-free survival or adverse events (AEs) were used. A total of 4994 patients from 8 RCTs were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.73; 95% CI, 0.61-0.89) versus chemotherapy in NSCLC patients who were less than 65 years old. Also, they prolonged the OS (HR, 0.74; 95% CI, 0.59-0.93) in NSCLC patients who were more than 65 years old. However, there was no statistical significance of OS (HR, 0.87; 95% CI, 0.57-1.30) among NSCLC patients who were more than 75 years old. It also showed that the single use of immune checkpoint inhibitors had fewer all-grade AEs. Regardless of the NSCLC patients who were less or more than 65 years, immune checkpoint inhibitors could achieve better OS than chemotherapy. But there was no significant difference when NSCLC patients who were more than 75 years old. Older patient should be offered immune therapies if it is possible and the mechanism in old age treatment should be further studied.


[Serratia marcescens nucleases. II. Primary structure analysis by peptide mapping combined with plasma-desorption mass spectrometry].
The primary structures of nucleases Sm1, Sm2, and Sm3 produced by Serratia marcescens were completely characterized using plasma desorption mass spectrometry (PDMS) of proteolytic peptides isolated by reverse-phase HPLC. The isoforms were separated by anion-exchange chromatography on DEAE cellulose and subjected to hydrolysis by the lysine-specific endoproteinase Lys-C. Comparative analysis of the peptides identified by PDMS showed that all three nucleases are N-terminal variants of the same protein: Sm2 represents a "mature" protein form, whereas Sm1 and Sm3 lack three and one N-terminal amino acid residues, respectively.


Regulation of Prescriptive Authority for Certified Nurse-Midwives and Certified Midwives: 2015 National Overview.
Statutory restrictions regarding the regulation of prescriptive authority for midwives continue to create barriers to practice in many states.


Computer aided analysis of gait patterns in patients with acute anterior cruciate ligament injury.
Gait analysis is a useful tool to evaluate the functional status of patients with anterior cruciate ligament injury. Pattern recognition methods can be used to automatically assess walking patterns and objectively support clinical decisions. This study aimed to test a pattern recognition system for analyzing kinematic gait patterns of recently anterior cruciate ligament injured patients and for evaluating the effects of a therapeutic treatment. Gait kinematics of seven male patients with an acute unilateral anterior cruciate ligament rupture and seven healthy males were recorded. A support vector machine was trained to distinguish the groups. Principal component analysis and recursive feature elimination were used to extract features from 3D marker trajectories. A Classifier Oriented Gait Score was defined as a measure of gait quality. Visualizations were used to allow functional interpretations of characteristic group differences. The injured group was evaluated by the system after a therapeutic treatment. The results were compared against a clinical rating of the patients' gait. Cross validation yielded 100% accuracy. After the treatment the score improved significantly (P<0.01) as well as the clinical rating (P<0.05). The visualizations revealed characteristic kinematic features, which differentiated between the groups. The results show that gait alterations in the early phase after anterior cruciate ligament injury can be detected automatically. The results of the automatic analysis are comparable with the clinical rating and support the validity of the system. The visualizations allow interpretations on discriminatory features and can facilitate the integration of the results into the diagnostic process.


Systems pharmacology-based exploration reveals mechanisms of anti-steatotic effects of Jiang Zhi Granule on non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD), which is in parallel with the obesity epidemic, accounts for a large amount of all chronic liver disease. Jiang Zhi Granule (JZG), a clinically used herbal formula, is developed in accordance with traditional Chinese medicine (TCM) pathogenesis for treating patients with NAFLD. In previous studies, the anti-steatotic effects of JZG against NAFLD have been demonstrated, and in this study, a systems pharmacology approach was used to explore the pharmacological mechanisms of JZG by predicting the active compounds within the herbal formula and their corresponding therapeutic targets. Its therapeutic efficacy was confirmed in the beginning of this study, and JZG was shown to significantly improve hepatic dysfunction and lipid droplet accumulation in PA-treated hepatocytes. Systems pharmacology was then performed to identify the active compounds in as well as to predict the therapeutic targets of this Chinese herbal prescription. Enrichment analyses indicated that the mechanisms of the anti-steatotic effects of JZG against NAFLD might be associated with lipid droplet degradation via autophagy, and a series of in vitro and in vivo validation experiments was subsequently performed to confirm that JZG could activate autophagy though the mTOR signalling to improve NAFLD.


An illustration of the technique of canonical analysis.
The use of a multivariate statistical technique, canonical analysis, for the assignment of patients to diagnostic categories is presented. The classification of thyroid status using clinical findings is investigated to exemplify the application of the technique. Emphasis is placed on the stages in the data analysis that are generic in examining any set of medical data for the purpose of automatically classifying patients.


Integrating 4-D light-sheet fluorescence microscopy and genetic zebrafish system to investigate ambient pollutants-mediated toxicity.
Ambient air pollutants, including PM2.5 (aerodynamic diameter d ~2.5 μm), PM10 (d ~10 μm), and ultrafine particles (UFP: d < 0.1 μm) impart both short- and long-term toxicity to various organs, including cardiopulmonary, central nervous, and gastrointestinal systems. While rodents have been the principal animal model to elucidate air pollution-mediated organ dysfunction, zebrafish (Danio rerio) is genetically tractable for its short husbandry and life cycle to study ambient pollutants. Its electrocardiogram (ECG) resembles that of humans, and the fluorescent reporter-labeled tissues in the zebrafish system allow for screening a host of ambient pollutants that impair cardiovascular development, organ regeneration, and gut-vascular barriers. In parallel, the high spatiotemporal resolution of light-sheet fluorescence microscopy (LSFM) enables investigators to take advantage of the transparent zebrafish embryos and genetically labeled fluorescent reporters for imaging the dynamic cardiac structure and function at a single-cell resolution. In this context, our review highlights the integrated strengths of the genetic zebrafish system and LSFM for high-resolution and high-throughput investigation of ambient pollutants-mediated cardiac and intestinal toxicity.


Device features and user behaviors as predictors of dependence among never-smoking electronic cigarette users: PATH Wave 4.
Electronic cigarettes (ECIGs) vary greatly in their ability to deliver nicotine, which suggests they may also vary in their ability to produce dependence. This study examined individual and combined ECIG device features, and also user behaviors, as predictors of dependence in never-smoking ECIG users. Methods Data were collected from 711 current ECIG users who had smoked <100 cigarettes in their lifetime at Wave 4 of the Population Assessment of Tobacco and Health (PATH) Study. Multivariable linear regressions examined individual (e.g., contains nicotine, uses a tank, flavor preference) and combined (e.g., refillable tanks, refillable mods) device features, and user behaviors (e.g., uses/day) as predictors of dependence, withdrawal, and craving after accounting for demographic variables. Results Results for ECIG dependence and craving showed a similar pattern; higher levels were observed for older age, more frequent past 30-day use, using an ECIG containing nicotine (vs no nicotine), and using a non-refillable cartridge or refillable tank style (vs disposables). Higher withdrawal levels were observed for higher education levels and individual device features of tank (vs no tank), cartridge (vs no cartridge), refillable (vs non-refillable), and "other" flavor preference (vs tobacco flavor). Lower withdrawal levels were associated with a preference for sweet/fruit flavor(s) (vs tobacco flavor). Conclusions Few use behaviors and device features, whether examined alone or in combination, predicted dependence-related outcomes. Findings underscore the challenge with regulating ECIG products in the current marketplace, which is inundated with a myriad of device types.


Gamma-irradiation produces active chlorine species (ACS) in physiological solutions: Secoisolariciresinol diglucoside (SDG) scavenges ACS - A novel mechanism of DNA radioprotection.
Secoisolariciresinol diglucoside (SDG), the main lignan in whole grain flaxseed, is a potent antioxidant and free radical scavenger with known radioprotective properties. However, the exact mechanism of SDG radioprotection is not well understood. The current study identified a novel mechanism of DNA radioprotection by SDG in physiological solutions by scavenging active chlorine species (ACS) and reducing chlorinated nucleobases. The ACS scavenging activity of SDG was determined using two highly specific fluoroprobes: hypochlorite-specific 3'-(p-aminophenyl) fluorescein (APF) and hydroxyl radical-sensitive 3'-(p-hydroxyphenyl) fluorescein (HPF). Dopamine, an SDG structural analog, was used for proton (1)H NMR studies to trap primary ACS radicals. Taurine N-chlorination was determined to demonstrate radiation-induced generation of hypochlorite, a secondary ACS. DNA protection was assessed by determining the extent of DNA fragmentation and plasmid DNA relaxation following exposure to ClO(-) and radiation. Purine base chlorination by ClO(-) and γ-radiation was determined by using 2-aminopurine (2-AP), a fluorescent analog of 6-aminopurine. Chloride anions (Cl(-)) consumed >90% of hydroxyl radicals in physiological solutions produced by γ-radiation resulting in ACS formation, which was detected by (1)H NMR. Importantly, SDG scavenged hypochlorite- and γ-radiation-induced ACS. In addition, SDG blunted ACS-induced fragmentation of calf thymus DNA and plasmid DNA relaxation. SDG treatment before or after ACS exposure decreased the ClO(-) or γ-radiation-induced chlorination of 2-AP. Exposure to γ-radiation resulted in increased taurine chlorination, indicative of ClO(-) generation. NMR studies revealed formation of primary ACS radicals (chlorine atoms (Cl) and dichloro radical anions (Cl2¯)), which were trapped by SDG and its structural analog dopamine. We demonstrate that γ-radiation induces the generation of ACS in physiological solutions. SDG treatment scavenged ACS and prevented ACS-induced DNA damage and chlorination of 2-aminopurine. This study identified a novel and unique mechanism of SDG radioprotection, through ACS scavenging, and supports the potential usefulness of SDG as a radioprotector and mitigator for radiation exposure as part of cancer therapy or accidental exposure.


The effect of tunicamycin and monensin on the association of Trypanosoma cruzi with resident macrophages.
The effect of incubation of parasites (epimastigote and trypomastigote forms of Trypanosoma cruzi) or macrophages in the presence of tunicamycin (TM) or monensin (M) on the parasite-macrophage association was analysed. Treatment of the parasites with TM, a drug which interferes with the process of N-glycosylation of proteins, increased by about 70% and decreased by about 27% the infection of epimastigote and trypomastigote forms, respectively. Treatment of the macrophages with TM increased by about 65% and reduced by about 45% the ingestion of epimastigote and trypomastigote forms, respectively. Treatment of the parasites or the macrophages with monensin, a drug which interferes with the sorting of membrane proteins, significantly reduced the ingestion of epimastigote and trypomastigote forms by the macrophages. The effects of both drugs were reversible. Treatment of the macrophages with trypsin followed by their incubation in fresh medium containing tunicamycin or monensin was used to analyse further the effects of these two drugs on the macrophages. The effects of the drugs on macrophages and parasites were controlled by electron microscopy. The results obtained suggest that the N-glycosylated proteins exposed on the surface of both cells are involved in the process of parasite-macrophage interaction and that interference in the process of sorting of membrane components alters the interaction.


The susceptibility of plasma coagulation factor XI to nitration and peroxynitrite action.
Coagulation factor XI is present in blood plasma as the zymogen, like other serine proteases of hemostatic system, but as the only coagulation factor forms 140-160kDa homodimers. Its activation is induced by thrombin, and a positive feedback increases the generation of the extra thrombin. Experimental and clinical observations confirm protective roles of factor XI deficiencies in certain types of thromboembolic disorders. Thromboembolism still causes serious problems for modern civilization. Diseases associated with the blood coagulation system are often associated with inflammation and oxidative stress. Peroxynitrite is produced from nitric oxide and superoxide in inflammatory diseases. The aim of the current study is to evaluate effects of nitrative stress triggered by peroxynitrite on coagulation factor XI in human plasma employing biochemical and bioinformatic methods. The amidolytic assay shows increase in factor XI activity triggered by peroxynitrite. Peroxynitrite interferes factor XI by nitration and fragmentation, which is demonstrated by immunoprecipitation followed by western blotting. Nitrated factor XI is even present in control blood plasma. The results suggest possible modifications of factor XI on the molecular level. Computer simulations show tyrosine residues as targets of peroxynitrite action. The modifications induced by peroxynitrite in factor XI might be important in thrombotic disorders.


Equine Facilitated Therapy for Complex Trauma (EFT-CT).
Emerging research suggests that Equine Facilitated Psychotherapy (EFP) may be beneficial for traumatized youth. In addition, complex trauma (i.e., multiple and/or prolonged developmentally adverse traumatic events which are typically interpersonal in nature) treatment research is still growing and there is a need for the development and examination of novel treatments for youth with complex trauma histories. The current article describes a promising EFP model for this population called Equine Facilitated Therapy for Complex Trauma (EFT-CT). EFT-CT embeds EFP practices within Attachment, Regulation and Competency (ARC), an extant evidence-based complex trauma treatment framework for children and adolescents. The authors provide three case studies using both observational data provided by clinicians, as well as longitudinal measures of psychosocial functioning, to illustrate the potential promise of EFT-CT. The article concludes with a discussion about implications for EFP treatment and research.


Protoplasting and Fluorescence-Activated Cell Sorting of the Shoot Apical Meristem Cell Types.
The shoot apical meristems (SAMs) are located at the tip of the shoot apex. The SAM harbors stem cells that divide continually to provide cells for developing above-ground organs. Several important developmental events occur in SAMs, such as stem cell maintenance, organ differentiation, and flowering commitment which are under genetic control. The SAM is a collection of specialized cells organized in specific spatial domains. Deciphering the gene regulatory networks, guided by the developmental and environmental signals, in these discrete cell types is essential to decoding the SAM function. Here, I provide updates to the previously published protocols for the protoplasting and subsequent purification through fluorescence-activated cell sorting (FACS) of SAM cell types (Reddy, Fluorescence activated cell sorting of shoot apical meristem cell types. In: Riechmann JL, Wellmer F (eds) Flower development. Methods in molecular biology, vol 1110. Humana, New York, pp 315-321, 2014), which has provided genome-wide gene expression patterns at a single cell-type resolution.


Dystonia in Childhood: How Insights from Paediatric Research Enrich the Network Theory of Dystonia.
Dystonia is now widely accepted as a network disorder, with multiple brain regions and their interconnections playing a potential role in the pathophysiology. This model reconciles what could previously have been viewed as conflicting findings regarding the neuroanatomical and neurophysiological characteristics of the disorder, but there are still significant gaps in scientific understanding of the underlying pathophysiology. One of the greatest unmet challenges is to understand the network model of dystonia in the context of the developing brain. This article outlines how research in childhood dystonia supports and contributes to the network theory and highlights aspects where data from paediatric studies has revealed novel and unique physiological insights, with important implications for understanding dystonia across the lifespan.


[Changes in the processes of bone marrow cell proliferation and differentiation in white mice under the influence of heparin].
In experiments carried out on albino mice daily heparin injections (250 units/kg) for two weeks resulted in 30% increase of leukocyte count in the venous blood. The femur bone marrow kariocyte count remained unchanged, while the leukoerythroblastic ratio rose from 4.1 to 7.6. Autoradiography demonstrated that the duration of the mitotic cycle and its phases in myeloid cells underwent no change, constituting: T--13 hrs, ts--8 hrs, tG2--1 hour, t(G1+M)--4 hrs. In heparinized animals the curve of labeled mitoses was nearly ideal. It is suggested that there occurred a change in the stem cells differentiation towards the myeloid type in the bone marrow under the effect of heparin.


Improving the precision of quantitative bottom-up proteomics based on stable isotope-labeled proteins.
Stable isotope dilution-based quantitative proteomics with intact labeled proteins as internal standards in combination with a bottom-up approach, i.e., with quantification on the peptide level, is an established method. To explore the technical precision of this approach, calmodulin-like protein 3 was prepared in non-labeled (light) and SILAC-type labeled (heavy) form by cell-free synthesis, mixed, digested with trypsin, and analyzed by UPLC-ESI-MS. In total, 16 light/heavy peptide pair ratios were determined. Pair-wise comparison of ratios of 12 peptides selected according to S/N ratios >50 revealed that the majority exhibited ratios, which were different at a high level of statistical significance (p < 0.001). HPLC-MALDI-MS ratio data confirmed this observation, thus excluding the ionization method as a source of the observed ratio differences. Variation of the digestion time from 0.25 to 4 h showed that the light/heavy ratios of most peptides decrease with time, indicating a kinetic isotope effect leading to preferred cleavage of light calmodulin-like protein 3. The subset of peptides with statistically identical ratios resulted in an average ratio with a RSD of 1.0 %. The light/heavy ratio calculated on the basis of these peptides probably provides the most accurate molar protein ratio.


Safety of adjunctive transvaginal beam therapy in the treatment of squamous cell carcinoma of the uterine cervix.
At The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1970 and 1980, 159 patients with bulky cervical cancers of FIGO Stages IB or II were treated with transvaginal orthovoltage radiotherapy (TVR) as an adjunct to standard external beam megavoltage irradiation and brachytherapy. The majority received 10 or 15 Gy air dose in 2-3 fractions using 125-250 kVp X rays. The dose from TVR was ignored in subsequent standard treatment planning. The absolute 5-year local control and survival rates were 82 and 83%, respectively. A total of 9 patients (5.7%) developed serious treatment complications that were significantly related to performance of a staging lymphadenectomy prior to radiotherapy and to an external beam pelvic dose of 50 +/- 0.5 Gy versus 40 +/- 0.5 Gy. The risk complications was not related to the dose of TVR or brachytherapy within the ranges used. Provided patients are properly selected and appropriate technical precautions are exercised, TVR is a safe technique. It is effective in controlling bleeding and shrinking large exophytic tumors, and very likely contributes to improved tumor control by facilitating optimal geometry for intracavitary therapy.


An anatomical study of the nasal superficial musculoaponeurotic system: surgical applications in rhinoplasty.
To give a unifying description of nasal muscles and ligaments corresponding to anatomical and surgical findings such as the dermocartilaginous ligament described by Pintanguy in 2001. In 30 fresh cadavers of white individuals, nasal dissections were performed, divided into 3 different approaches: from radix to nasal tip, from nasal tip to radix, and from midline to lateral. The anatomical and surgical planes of dissection were followed to isolate the nasal superficial musculoaponeurotic system (SMAS). Correlations between the nasal SMAS and the nasal framework were noticed. In 9 specimens, the left nasal wall was resected for histologic examination. The nasal SMAS consists of a unique layer, and it divides at the level of the nasal valve into deep and superficial layers. Each layer has medial and lateral components. The dermocartilaginous ligament corresponds to the deep medial expansion. Both the deep and the superficial medial expansions correspond to the lowering ligaments of the nasal tip; the cephalic rotation of the nasal tip is allowed by their cut. The histological examination showed that the deep lateral expansion is composed of fat. This description of the nasal SMAS explains the relationship between the nasal muscles and ligaments, including the dermocartilaginous ligament described by Pitanguy. Furthermore, it is helpful to surgeons during rhinoplasty.


[Multilocular progressive lipoatrophia semicircularis].
Report on a 51-year-old adipose patient suffering from a rapidly progressing lipatrophia semicircularis. The lipoatrophy occurred in the form of numerous lesions on the trunk and limbs.


The ratio of CD163-positive macrophages to Iba1-positive macrophages is low in the intima in the early stage of cutaneous arteritis.
The etiology of polyarteritis nodosa (PAN) and localized PAN, including cutaneous arteritis (CA), remains unknown; however, initial endothelial damage has been implicated. The intima of the vasculitis lesions is predominantly infiltrated by innate-like bystander-activated CD8 T cells, in addition to the macrophages. Macrophages are among the major inflammatory cells involved in innate immunity and are classified into M1 and M2 subtypes. M1-type macrophages kill pathogens and cause inflammation, while M2-type macrophages promote the repair of tissues. Macrophage subtypes infiltrating in PAN and localized PAN vasculitis lesions have not yet been investigated. Innate immune response to a triggering factor on the endothelial cell surface may initiate CA pathogenesis. Thus, many M1-type macrophages may infiltrate in the intima during early CA. We assessed this hypothesis by immunohistochemical observation of macrophage phenotypes and polarization. Twenty-seven skin biopsy specimens from patients with CA were retrieved. Based on histology, we classified CA into four phases. The phenotypes of infiltrating macrophages in CA were evaluated by immunohistochemistry using antibodies against Iba-1, a pan-macrophage marker, and CD163, an M2-type macrophage marker. Our results showed that the ratio of CD163-positive M2-type macrophages to Iba1-positive macrophages was lower in the intima in the early stage of CA than in the later stage. In the media to adventitia, there was no significant difference in the ratios between these stages. These findings indicate that innate immunity is involved in the intima in the early stage of CA, suggesting that a trigger for CA might exist in endothelial cells.


Influence of heme oxygenase-1 on microcirculation after kidney transplantation.
Cytoprotective proteins, such as heme oxygenase-1 (HO-1), play a decisive role in ischemia-reperfusion injury during kidney transplantation. The aim of this study was to investigate the impact of heme oxygenase-1 on microcirculation and on ischemia-reperfusion injury in an isogenic kidney transplantation rat model. Seventy male Lewis rats were distributed into three groups. In Group 1(control), the kidneys were only mobilized. In Groups 2 and 3, bilateral nephrectomy was performed, and a kidney from another Lewis rat was orthotopically transplanted on the left side. The donor animals in Group 3 received preconditioning with the HO-1 inductor hemin. 24 h after reperfusion graft function and morphology were examined. Microcirculation was investigated by in vivo microscopy of the renal surface 1 h after reperfusion. HO-1 preconditioning led to significantly lower serum creatinine and serum urea, as well as less histological damage and inducible nitric oxide synthase expression. Microcirculation was improved by a significant enlargement of the vascular diameter and an increase of the capillary flow. Treatment with hemin improves microcirculation by induction of HO-1 and reduces ischemia-reperfusion injury after kidney transplantation. HO-1 induction was shown to be a promising approach in the preconditioning of donor kidneys.


Transport of proteins across the mitochondrial outer membrane. A precursor form of the cytoplasmically made intermembrane enzyme cytochrome c peroxidase.
Cytochrome c peroxidase, a cytoplasmically made enzyme located between the inner and outer membrane of yeast mitochondria, is synthesized as larger precursor in a reticulocyte cell-free lysate as well as in pulsed yeast spheroplasts. When the pulsed spheroplasts are chased, the precursor is converted to the mature apoprotein. When the in vitro synthesized precursor is incubated with isolated yeast mitochondria in the absence of protein synthesis, it is cleaved to the mature form; the mature form co-sediments with the mitochondria and is resistant to externally added proteases. These results, in conjunction with those reported earlier (Maccecchini, M.-L., Rudin, Y., Blobel, G., and Schatz, G. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 343-347) suggest that the mechanism of protein transport into the mitochondrial intermembrane space is quite similar to that of protein transport into the matrix or the inner membrane.


Uptake of selected PAHs from contaminated soils by rice seedlings (Oryza sativa) and influence of rhizosphere on PAH distribution.
The uptake of selected polycyclic aromatic hydrocarbons (PAHs) by rice (Oryza sativa) seedlings from spiked aged soils was investigated. When applied to soils aged for 4 months, naphthalene, phenanthrene, and pyrene exhibited volatilization loss of 98, 95, and 30%, respectively, with the remaining fraction being fixed by soil organic matter and/or degraded by soil microbes. In general, concentrations of the three PAHs in rice roots were greater than those in the shoots. The concentrations of root associated PHN and PYR increased proportionally with both soil solution and rhizosphere concentrations. PAH concentrations in shoots were largely independent of those in soil solution, rice roots, or rhizosphere soil. The relative contributions of plant uptake and plant-promoted rhizosphere microbial biodegradation to the total mass balance were 0.24 and 14%, respectively, based on PYR concentrations in rhizosphere and non-rhizosphere soils, the biomass of rice roots, and the dry soil weight.


spn-A/rad51 mutant exhibits enhanced genomic damage, cell death and low temperature sensitivity in somatic tissues.
Homologous recombination (HR) is one of the key pathways to repair double-strand breaks (DSBs). Rad51 serves an important function of catalysing strand exchange between two homologous sequences in the HR pathway. In higher organisms, rad51 function is indispensable with its absence leading to early embryonic lethality, thus precluding any mechanistic probing of the system. In contrast, the absence of Drosophila rad51 (spn-A/rad51) has been associated with defects in the germline, without any reported detrimental consequences to Drosophila somatic tissues. In this study, we have performed a systematic analysis of developmental defects in somatic tissues of spn-A mutant flies by using genetic complementation between multiple spn-A alleles. Our current study, for the first time, uncovers a requirement for spn-A in somatic tissue maintenance during both larval and pupal stages. Also, we show that spn-A mutant exhibits patterning defects in abdominal cuticle in the stripes and bristles, while there appear to be only subtle defects in the adult wing and eye. Interestingly, spn-A mutant shows a discernible phenotype of low temperature sensitivity, suggesting a role of spn-A in temperature sensitive cellular processes. In summary, our study describes the important role played by spn-A/rad51 in Drosophila somatic tissues.


Robotically assisted retroperitoneoscopic heminephrectomy in children: initial clinical results.
To investigate the feasibility of robotically assisted retroperitoneoscopic upper pole heminephrectomy with the Da Vinci Surgical System. Fourteen girls (median age 4.9 years, range 0.5-20.2) underwent upper pole heminephrectomy using the retroperitoneal approach with the Da Vinci Surgical System. Prior to all procedures a ureteric catheter was placed. Using a modified access to the retroperitoneum the ureter to the upper pole and the vessels were dissected and ligated. The upper pole was removed by diathermy or ultrasonic scissors. The median operative time was 176 min (range 120-360 min). In two patients, the procedure was converted to an open operation; in one case due to lack of progress, and in the other due to bleeding which could not be handled with the robotically assisted instruments. One patient had the ureteric stump removed due to recurrent infections. In all other patients the peri- and postoperative period was uneventful. The robotically assisted system is an excellent tool for minimally invasive surgery in the retroperitoneum, such as pyeloplasty, with its advantages of wrist-like movements of the instruments, magnified three-dimensional view, tremor control and improved ergonomics for the surgeon. Further development of the instruments is required before the resection of a non-functioning upper pole can be included in the spectrum of indications.


Antihypertensive compounds with potent protein kinases inhibitory activity.
A new indorocarbazole antibiotic SF2370 has been found in the culture broth of Actinomadura sp.; it has also been found to have the activities of antihypertension and diuresis. Derivatives of SF2370, NA0344, NA0345 and NA0346, when injected (0.1-1 mg/kg i.v.) significantly lowered the blood pressure of anesthetized normotensive rats and showed a long lasting antihypertensive action. In the case of p.o. administration to conscious restrained SHRs, measurement of blood pressure by the plethysmographic method indicated that 10 mg/kg of the compounds was enough to lower the blood pressure; the antihypertensive activities were found to remain more than 12 hrs after oral administration. By studying of the mode of antihypertensive action, these compounds dose dependently relaxed the isolated aortic preparation contracted by norepinephrine. In addition, it was found that protein kinase C activity of mice brain was inhibited by the compounds; the IC50 values were in the range of 0.062-0.20 microM. Moreover, a superprecipitation of actomyosin from smooth muscle of chicken gizzard was inhibited by the compounds, having an IC50 values of 0.31-0.72 microM.


Non-destructive techniques for the determination of magnetic particle and element contents in grapevine leaves and soil as an eco-sustainable tool for environmental pollution assessment in the agricultural areas.
The concentration of magnetic particulate matter (PM) on the leaf surface (an indicator of current pollution) and topsoil (an indicator of magnetic PMs which have geogenic natural signal or historical pollution origin) was assessed in agricultural areas (conventional and organic vineyards). The main aim of this study was to explore whether magnetic parameters such as saturation isothermal remanent magnetization (SIRM) and mass-specific magnetic susceptibility (χ) can be a proxy for magnetic particulate matter (PM) pollution and associated potentially toxic elements (PTEs) in agricultural areas. Besides, wavelength dispersive X-ray fluorescence spectroscopy (WD-XRF) was investigated as a screening method for total PTE content in soil and leaf samples. Both magnetic parameters (SIRM and χ) pinpoint soil pollution, while SIRM was more suitable for evaluating magnetic PM accumulated on leaves. The values of both magnetic parameters were significantly (p < 0.01) correlated within the same type of sample (soil-soil or leaf-leaf), but not between different matrixes (soil-leaf). Differences between magnetic particles' grain sizes among vegetation seasons in vineyards were obtained by observing the SIRM/χ ratio. WD-XRF was revealed to be an appropriate screening method for soil and leaf total element contents in agricultural ambient. For a more precise application of WD-XRF leaf measurements, specific calibration using a similar matrix to plant material is required. In parallel, measurements of SIRM, χ, and element content (by WD-XRF) can be recommended as user-friendly, fast, and eco-sustainable techniques for determining magnetic PM and PTE pollution hotspots in agricultural ambient.


Environmental exposure to manganese in air: Tremor, motor and cognitive symptom profiles.
Excessive exposure to manganese (Mn) may cause parkinsonian-like motor and tremor symptoms and adverse cognitive effects, including problems with executive functioning (EF), resembling those found in later-stage Parkinson's disease (PD). Studies seeking to differentiate PD patients into subgroups with associated cognitive and functional outcomes using motor and tremor symptoms identified tremor-dominant (TD) and non-tremor dominant (NTD) subtypes. It is unclear whether differing patterns of pathophysiology and symptoms exist in Mn neurotoxicity, as they do in PD. Residents of East Liverpool (n=83) and Marietta, OH (n=99) exposed to chronic (>10years) environmental Mn through industrial pollution were administered neuropsychological measures and a physician-rated scale of movement-disorder symptoms. Two-step cluster analysis was used to group residents based on tremor symptoms, bradykinesia/rigidity symptoms, gait disturbance, and executive function. Cluster membership was validated using modeled air-Mn exposure and a computerized tremor measure. Elevated tremor and motor symptoms and executive dysfunction were observed, and TD and NTD symptom clusters were identified. Two additional clusters were also identified: Executive Dysfunction and Normal Functioning. The NTD residents, with elevated levels of gait disturbance and other movement disorder symptoms, did not evidence EF impairment, as predicted. Instead, residents with EF impairment formed their own cluster, and were relatively free of movement disorder symptoms. Results resemble reports in the PD literature with TD and NTD clusters identified, but executive dysfunction did not cluster with NTD symptoms. PD and Mn exposure likely have differing pathophysiology and developmental courses, and therefore different symptom patterns, even when similar symptoms are present.


The dual klepsydra model of internal time representation and time reproduction.
We present a model of the internal representation and reproduction of temporal durations, the 'dual klepsydra' model (DKM). Unlike most contemporary models operating on a 'pacemaker-counter' scheme, the DKM does not assume an oscillatory process as the internal time-base. It is based on irreversible, dissipative processes in inflow/outflow systems (leaky klepsydrae), whose states are continuously compared; if their states are equal, durations are subjectively perceived as equal. Model-based predictions fit experimental time reproduction data with good accuracy, and show qualitative features not accounted for by other models. The deterministic model is characterized by two parameters, kappa (outflow rate coefficient) and eta (ratio of inflow rates). A stochastic version of the model (SDKM) assumes randomly fluctuating inflows, involves two more parameters, and accounts for intra-individual variance of reproduced durations. Analysis of the SDKM leads to non-trivial problems in the stochastic theory, briefly sketched here. Methods of parameter estimation for both deterministic and stochastic versions are given. Applying the DKM to the subjective experience of time passage, we show how subjective measure of elapsed time is constituted. Finally, essential features of the model and its possible neurophysiological interpretation are discussed.


Overexpression of a Domain of Unknown Function 266-containing protein results in high cellulose content, reduced recalcitrance, and enhanced plant growth in the bioenergy crop Populus.
Domain of Unknown Function 266 (DUF266) is a plant-specific domain. DUF266-containing proteins (DUF266 proteins) have been categorized as 'not classified glycosyltransferases (GTnc)' due to amino acid similarity with GTs. However, little is known about the function of DUF266 proteins. Phylogenetic analysis revealed that DUF266 proteins are only present in the land plants including moss and lycophyte. We report the functional characterization of one member of DUF266 proteins in Populus, PdDUF266A. PdDUF266A was ubiquitously expressed with high abundance in the xylem. In Populus transgenic plants overexpressing PdDUF266A (OXPdDUF266A), the glucose and cellulose contents were significantly higher, while the lignin content was lower than that in the wild type. Degree of polymerization of cellulose in OXPdDUF266A transgenic plants was also higher, whereas cellulose crystallinity index remained unchanged. Gene expression analysis indicated that cellulose biosynthesis-related genes such as CESA and SUSY were upregulated in mature leaf and xylem of OXPdDUF266A transgenic plants. Moreover, PdDUF266A overexpression resulted in an increase of biomass production. Their glucose contents and biomass phenotypes were further validated via heterologous expression of PdDUF266A in Arabidopsis. Results from saccharification treatment demonstrated that the rate of sugar release was increased by approximately 38% in the OXPdDUF266A transgenic plants. These results suggest that the overexpression of PdDUF266A can increase cellulose content, reduce recalcitrance, and enhance biomass production, and that PdDUF266A is a promising target for genetic manipulation for biofuel production.


Environmental risk assessment of metals contaminated soils at silvermines abandoned mine site, Co Tipperary, Ireland.
A centuries long history of mining and mineral processing has resulted in elevated Cd, Pb and Zn soil concentrations in the vicinity of the Silvermines abandoned mine site (AMS), Co. Tipperary, Ireland. A process for preliminary evaluation of environmental risk was developed and implemented. Potential pathways of metal compound transport and deposition were mapped and used to optimise the subsequent site investigation. Elevated soil metals are shown to be predominantly in areas where metal deposition in soil is associated with water related pathways (surface runoff, seasonal groundwater seepage and floodplains). Extensive areas of soil in the surrounding district are classified as contaminated on the basis of Cd, Pb and Zn concentrations, both total and potential bioavailable (EDTA-extractable). The most affected areas, with metal concentrations in soil comparable with that within the AMS, were floodplains located 2-3 km downstream from the site. Assessment of the sequential effects on grass and grazing animals indicates that Pb poses the greatest risk due to its high toxicity and high concentrations in soil (more than 10,000 mg kg-1). Within floodplain areas grazing cattle may intake a lethal dose of Pb. On the basis of the investigation an approach to risk assessment was developed which allowed quantified assessment of the risks related to individual metals, areas of contamination and contamination targets.


Paraparesis due to metastatic prostatic cancer effectively treated with a high dose of diethylstilbestrol diphosphate: a case report.
A case of paraparesis due to thoracic vertebula metastasis of prostate cancer is reported. Treatment through a high dose of diethylstilbestrol diphosphate (DES-P) was very effective. Two and a half years later, the patient is ambulatory and relapse has not occurred. We recommend the use of a high dose of DES-P for spinal cord compression due to prostate cancer, instead of laminectomy or radiation.


Flibanserin and Female Sexual Desire.
Female hypoactive sexual desire disorder (HSDD) is one type of sexual problem that can affect women. It is characterized by low or absent sexual desire that cannot be attributed to another cause and results in difficulty in interpersonal relationships. HSDD is not well understood, and women may not report symptoms of difficulties to their health care providers. In August 2015, the U.S. Food and Drug Administration approved flibanserin, a nonhormonal oral medication for the treatment of HSDD in premenopausal women. Flibanserin is the only currently available pharmacologic treatment for HSDD. This article will provide an overview of flibanserin, including potential adverse reactions, special considerations for use, and implications for nursing practice.


Vaccination with a Porcine Reproductive and Respiratory Syndrome (PRRS) Modified Live Virus Vaccine Followed by Challenge with PRRS Virus and Porcine Circovirus Type 2 (PCV2) Protects against PRRS but Enhances PCV2 Replication and Pathogenesis Compared to Results for Nonvaccinated Cochallenged Controls.
Coinfections involving porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) contribute to a group of disease syndromes known as porcine circovirus-associated disease (PCVAD). Presumably, PRRSV infection enhances PCV2 replication as a result of modulation of host immunity. The purpose of this study was to evaluate PCV2 replication and pathogenesis in pigs vaccinated with a PRRS modified live virus (MLV) vaccine and subsequently challenged with a combination of PRRSV and PCV2. During the early postchallenge period, the number of pigs with PRRSV-associated clinical signs was decreased, and average daily gain (ADG) was increased, in the vaccinated group, demonstrating the protective effect of PRRS vaccination. However, during the later postchallenge period, more pigs in the vaccinated group showed increased PCV2 viremia, decreased ADG, increased PCVAD clinical signs, and increased mortality. In this disease model, the early benefits of PRRSV vaccination were outweighed by the later amplification of PCVAD.


The use of an immunoperoxidase technique to investigate by light and electron microscopy the sites of binding of Clostridium welchii type-D epsilon toxin in mice.
Mice were given an intravenous dose of formalinised C. welchii type-D epsilon prototoxin and an immunoperoxidase technique was used to demonstrate this antigen in the tissues. The antigen was found to bind to the luminal surface of the endothelial lining of certain blood vessels, to the luminal surface of the cells lining the loops of Henlé and distal convoluted tubules in the kidney, and to the hepatic sinusoids. As it has been shown previously that formalinised epsilon prototoxin and epsilon toxin can compete for the same receptor sites it is postulated that the binding sites demonstrated represent the location of the receptors for C. welchii type-D epsilon toxin.


Sexual abuse history and treatment outcomes among women undergoing methadone treatment.
Women entering drug abuse treatment programs who report a history of sexual abuse are also likely to report poorer psychosocial functioning, more drug-related problems, and more family-of-origin problems. This study investigates outcome differences at follow-up between women with and those without sexual abuse histories who were treated at an outpatient methadone treatment program. Follow-up interviews were conducted with 98 women, 40% of whom reported prior sexual abuse. Those with a history of sexual abuse who reported problems at intake with psychosocial functioning and family support continued to report such problems at follow-up as compared with the women without a history of sexual abuse. However, no difference was found at follow-up between women with and those without sexual abuse histories in terms of drug use, employment, criminality, or HIV-risky behaviors. The findings suggest that sexual abuse history alone cannot predict treatment outcomes for women in methadone treatment. The implications of these findings are discussed in terms of treatment process and services.


New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance.
Chondrosarcomas are cartilage-forming, poorly vascularized tumors. They represent the second malignant primary bone tumor of adults after osteosarcoma, but in contrast to osteosarcoma they are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. Few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown. Our goal was to establish new cell lines and animal cancer models from human chondrosarcoma biopsies to study their chemoresistance. Between 2007 and 2012, 10 chondrosarcoma biopsies were collected and used for cell culture and transplantation into nude mice. Only one transplanted biopsy and one injected cell line has engrafted successfully leading to conventional central high-grade chondrosarcoma similar to the original biopsies. In culture, two new stable cell lines were obtained, one from a dedifferentiated and one from a grade III conventional central chondrosarcoma biopsy. Their genetic characterization revealed triploid karyotypes, mutations in IDH1, IDH2, and TP53, deletion in CDKN2A and/or MDM2 amplification. These cell lines expressed mesenchymal membrane markers (CD44, 73, 90, 105) and were able to produce a hyaline cartilaginous matrix when cultured in chondrogenic three-dimensional (3D) pellets. Using a high-throughput quantitative RT-PCR approach, we observed that cell lines cultured in monolayer had lost expression of several genes implicated in cartilage development (COL2A1, COMP, ACAN) but restored their expression in 3D cultures. Chondrosarcoma cells in monolayer were sensitive to several conventional chemotherapeutic agents but became resistant to low doses of mafosfamide or doxorubicin when cultured in 3D pellets, in parallel with an altered nucleic accumulation of the drug. Our results indicate that the cartilaginous matrix produced by chondrosarcoma cells may impair diffusion of several drugs and thus contribute to chemoresistance. Therefore, 3D chondrogenic cell pellets constitute a more relevant model to study chondrosarcoma chemoresistance and may be a valuable alternative to animal experimentations.


Journal of family medicine and primary care- A five year bibliometric analysis from 2016 to 2020.
To conduct a five-year bibliometric analysis of the Journal of Family Medicine and Primary Care (J Family Med Prim Care) between 2016 and 2020. This retrospective secondary data analysis was conducted in the Department of Conservative, Endodontics and Aesthetic Dentistry, Dental Institute, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand and Rohilkhand Medical College and Hospital, Bareilly, UP. The data of publications including research articles, review and case reports excluding editorials and letters to the editor, commentaries and invited articles published in the J Family Med Prim Care between 2016 and 2020 were downloaded from the journal website and analysed in terms of the bibliometric parameters. The results revealed that the journal gave equal weightage to all types of articles. The total number of articles published between 2016 and 2020 was 2,426 out of which 1,666 articles were published from India and the remaining from other parts of the world. In India, the state of Delhi had the maximum publications while speciality Preventive and Social Medicine (22.42%) and General Medicine (23.12%) had the maximum articles. Moreover, between 2016 and 2020, J Family Med Prim Care had 2,132 citations of published articles and had 65 publications in 2020 about the Corona Virus Disease (COVID-19) pandemic. The issue numbers per year for J Family Med Prim Care has gradually increased over time. The publication is open for all fields of medical, dental sciences and allied sciences.


Effects of ACTH and 3',5'-cyclic purine nucleotides on the morphology and metabolism of normal adult human adrenocortical cells in primary tissue culture.
Stereological studies showed that treatment of normal adult human adrenocortical cells in primary culture with ACTH or cyclic-AMP for 2 days results in similar increases in the volume of cells, of the mitochondrial and "membrane space" compartments and of the surface area of the smooth endoplasmic reticulum and mitochondrial cristae, and decrease in the lipid content of the cells. These changes were more marked after 8 days of treatment. Treatment for 2 days with cyclic-GMP had no striking effects on cell ultrastructure, whereas an 8-day treatment led to ultrastructural changes similar to those obtained after 2 days of ACTH- or cyclic-AMP-treatment. A discrete population of untreated cortical cells maintained a slow proliferation that was not effected by exposure to cyclic-GMP, but was significantly increased in cultures treated with ACTH or cyclic-AMP. Radioimmunological studies showed that untreated cortical cells kept secreting progesterone and cortisol and that ACTH, but neither cyclic nucleotide, increased the secretion rate per cell of both hormones. These results assign a major role to cyclic-AMP and a minor one to cyclic-GMP in the mediation of the differentiation-promoting and trophic effects, but not in the steroidogenic effects of ACTH on the human adrenal cortex.


Immune-related pathogenesis and therapeutic strategies of nonalcoholic steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and has become prevalent in the adult population worldwide, given the ongoing obesity pandemic. NAFLD comprises several hepatic disorders, ranging from fatty liver to nonalcoholic steatohepatitis (NASH), cirrhosis, and carcinoma. Excessive fat accumulation in the liver can induce the development of fatty liver, whereas the progression of fatty liver to NASH involves various complex factors. The crucial difference between fatty liver and NASH is the presence of inflammation and fibrosis, the emergence of which is closely associated with the action of immune cells and immunological factors, such as chemokines and cytokines. Thus, expanding our understanding of immunological mechanisms contributing to NASH pathogenesis will lead to the identification of therapeutic targets and the development of viable therapeutics against NASH.


Correction to: 'Sprinting with prosthetic versus biological legs: insight from experimental data' (2023) by Beck et al.
[This corrects the article DOI: 10.1098/rsos.211799.][This corrects the article DOI: 10.1098/rsos.211799.].


Use of skeletal muscle MRI in diagnosis and monitoring disease progression in Duchenne muscular dystrophy.
Studies have shown promise in using various approaches of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy to evaluate skeletal muscle involvement in Duchenne muscular dystrophy. However, these studies have mainly been performed using a cross-sectional design, and the correlation of these MRI changes with disease progression and disease severity has not been fully elucidated. Overall, skeletal muscle MRI is a powerful and sensitive technique in the evaluation of muscle disease, and its use as a biomarker for disease progression or therapeutic response in clinical trials deserves further study.


Enhanced Thermoelectric Performance of n-Type Organic Semiconductor via Electric Field Modulated Photo-Thermoelectric Effect.
Modulating photophysical processes is a fundamental way for tuning performance of many organic devices. However, it has not been explored as an effective strategy to manipulate the thermoelectric (TE) conversion of organic semiconductors (OSCs) owing to their critical requirement to carrier concentration (>1018 cm-3 ) and the fact of low exciton separation efficiency in single element OSCs. Here, an electric field modulated photo-thermoelectric (P-TE) effect in an n-type OSC is demonstrated to realize a significant improvement of TE performance. The electrical and spectroscopy characterizations reveal that the electric field gating generates combined modulation of exciton separation, charge screening, and carrier recombination, which produces a more than ten times improvement of photoinduced carrier concentration. These coupled processes contribute to the unconventional Seebeck coefficient (S)-electrical conductivity (σ) trade-off relationship of the photoexcited films, therefore leading to a more than 500% enhancement in the power factor for n-type OTE semiconductors. This work opens a unique way toward state-of-the-art organic P-TE materials for energy harvesting applications.


Crossing the Gateless Barriers: Factors Involved in the Movement of Circulative Bacteria Within Their Insect Vectors.
Plant bacterial pathogens transmitted by hemipteran vectors pose a large threat to the agricultural industry worldwide. Although virus-vector relationships have been widely investigated, a significant gap exists in our understanding of the molecular interactions between circulative bacteria and their insect vectors, mainly leafhoppers and psyllids. In this review, we will describe how these bacterial pathogens adhere, invade, and proliferate inside their insect vectors. We will also highlight the different transmission routes and molecular factors of phloem-limited bacteria that maintain an effective relationship with the insect host. Understanding the pathogen-vector relationship at the molecular level will help in the management of vector-borne bacterial diseases.


A computerized perinatal data system for a region.
The development of regionalized systems for perinatal care requires a record system which will provide a flow of patient information to and from referring and center hospitals. It should also provide for the risk evaluation of patients being cared for within the region as well as for the quality and statistical evaluation. When the Arizona Perinatal Program was established in 1975 with funding by the Robert Wood Johnson Foundation, the decision was made to adopt and expand a perinatal data system under development at St. Joseph's Hospital in Phoenix. This data system is made up of two major components: (1) a paper record system in which the documents completed by physician or nurse serve both as the medical record and a computer-input document and (2) a computer capable of simultaneous communication with 17 different terminals, directly or by telephone lines. Programs to meet the goals of patient care, quality evaluation, and statistical assessment are described.


Presumptive positive with the Cepheid Xpert Xpress SARS-CoV-2 assay due to N mutations in the Delta variant.
The Cepheid Xpert® Xpress SARS-CoV-2 assay is 1 of the several real-time reverse transcription polymerase chain reaction (RT-PCR) assays that received Emergency Use Authorization from the United States Food and Drug Administration (FDA) for detection of SARS-CoV-2. Here we report 4 SARS-CoV-2 samples that were reported as presumptive positives on the Cepheid platform while reported as positives on alternative RT-PCR platforms. Whole genome sequencing indicated that the samples were Delta variants and had point mutations in the N gene which potentially interfered with SARS-CoV-2 detection. Two types of point mutations were found in these samples in the US CDC 2019-nCoV Real time PCR N2 Probe region: C29203T and C29200T. C29203T is a novel point mutation, and C29200T has not been previously reported in the Delta variants. This underlines the fact that mutations in the real-time RT-PCR assay target region could hinder accurate detection of SARS-CoV-2.


Early in vivo MR spectroscopy findings in organophosphate-induced brain damage-potential biomarkers for short-term survival.
Organophosphates are highly toxic substances, which cause severe brain damage. The hallmark of the brain injury is major convulsions. The goal of this study was to assess the spatial and temporal MR changes in the brain of paraoxon intoxicated rats. T2-weighted MRI and ¹H-MR-spectroscopy were conducted before intoxication, 3 h, 24 h, and 8 days postintoxication. T2 prolongation mainly in the thalami and cortex was evident as early as 3 h after intoxication (4-6% increase in T2 values, P < 0.05). On spectroscopy, N-acetyl aspartate (NAA)/creatine and NAA/choline levels significantly decreased 3 h postintoxication (>20% decrease, P < 0.005), and 3 h lactate peak was evident in all intoxicated animals. On the 8th day, although very little T2 changes were evident, NAA/creatine and choline/creatine were significantly decreased (>15%, P < 0.05). Animals who succumbed had extensive cortical edema, significant higher lactate levels and a significant decrease in NAA/creatine and NAA/choline levels compared to animals which survived the experiment. Organophosphates-induced brain damage is obvious on MR data already 3 h postintoxication. In vivo spectroscopic changes are more sensitive for assessing long-term injury than T2-weighted MR imaging. Early spectroscopic findings might be used as biomarkers for the severity of the intoxication and might predict early survival.


Determinants of esophageal acid clearance in normal subjects.
In this study, we evaluated factors that affect esophageal acid clearance in normal subjects. A 15-ml bolus of 0.1 N HCl (pH 1.2) was injected into the esophagus, and the subject then swallowed every 30 s. Manometric and pH monitoring demonstrated that esophageal acid clearance occurred by a series of step increases in pH, each associated with a swallow-induced peristaltic sequence. Between peristaltic sequences, pH increase was minimal. Saliva stimulation by oral lozenge greatly improved acid clearance, while oral aspiration of saliva abolished the step increases in esophageal pH and markedly delayed acid clearance. Replacement of aspirated saliva with a bicarbonate solution reproduced the step increases in esophageal pH and restored acid clearance toward normal, while replacement with water alone failed to improve acid clearance. Similar to the effect of the oral lozenge, bethanechol (5 mg subcutaneously) improved esophageal acid clearance, but this improvement was reversed by oral aspiration of saliva, which markedly delayed acid clearance. A change from the recumbent to the sitting position tended to improve acid clearance slightly, but this improvement was not statistically significant. We concluded that in normal subjects (a) swallowing carries saliva into the esophagus and peristalsis empties intraesophageal fluid into the stomach, (b) the neutralization of acid by saliva carried into the esophagus with each swallow accounts for the occurrence of acid clearance by step increases in pH, (c) the improvement in acid clearance with bethanechol is due to saliva stimulation, and (d) gravity contributes little to esophageal acid clearance in the presence of normal peristaltic stripping waves.


Isolation of Reprogramming Intermediates During Generation of Induced Pluripotent Stem Cells from Mouse Embryonic Fibroblasts.
Mature cells of the body can be reprogrammed towards a pluripotent state by forced expression of the transcription factors Oct-4, Klf-4, Sox2, and C-Myc (OKSM) at very low efficiency. To study the reprogramming process in detail the rare intermediates of the reaction need to be separated from the bulk population. Using a genetically engineered reprogrammable mouse strain we describe how to isolate intermediates from reprogramming cultures of mouse embryonic fibroblasts via antibody labeling of cell surface markers and fluorescence-activated cell sorting (FACS).


Inhibitory effect of metformin therapy on the incidence of colorectal advanced adenomas in patients with diabetes.
Metformin use has been associated with decreased colorectal cancer risk and mortality among diabetic patients. Recent research suggests that metformin use may decrease the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. This study aimed to assess the clinical effect of metformin use on the development of colorectal adenomas in diabetic patients without previous colorectal cancer. Among 604 consecutive diabetic patients who underwent colonoscopic surveillance after initial colonoscopy between January 2002 and June 2012, 240 patients without previous colorectal cancer were enrolled in this study and were divided in two groups: 151 patients receiving metformin and 89 patients not receiving metformin. Patient demographics and clinical characteristics as well as the colorectal adenoma incidence rate were retrospectively analyzed. The incidence rate of total colorectal adenomas was not different according to metformin use (P=0.349). However, the advanced adenoma incidence rate was significantly lower in the metformin group compared with the non-metformin group (relative risk [RR], 0.09; P=0.011). Metformin use was independently associated with a decreased incidence of advanced colorectal adenomas after adjustment for clinically relevant factors (RR, 0.072; P=0.016). In addition, the cumulative development rate of advanced adenomas during follow-up was significantly lower in the metformin group compared with the non-metformin group (P=0.007). Metformin use in diabetic patients without previous colorectal cancer is associated with a lower risk of advanced colorectal adenomas.


Introduction and uptake of electronic growth charts in southern New Zealand.
The introduction of an electronic system for recording and displaying growth measurements replaces multiple paper growth charts and theoretically improves the availability and consistency of information to support clinical decision-making. Introducing this in a single New Zealand District Health Board provided the opportunity to evaluate usage in hospital settings and determine the uptake of growth recording in a defined population. All records between 2010 and 2015 in the Southern District Health Board (SDHB) anthropometry database were downloaded and examined in a retrospective cohort analysis. Records were extracted after matching to demographic and clinical setting data from the hospital patient management system. Analysis included 30 670 data entry points, representing 8551 children. Data entry increased over time to a maximum of 8407 observations in 2015. By the fifth year of use, up to 67% of available clinical encounters had anthropometry recorded in the outpatient department. Rates were lower in the inpatient setting, where only up to 18.4% had anthropometry recorded. The errors identified were low (0.2% of all data). Weight was the most commonly recorded measurement (98.2% of anthropometry entries, 35.1% of available clinical presentations). Height was available for 82.6% of entries and 29.5% of presentations. A body mass index z-score was available for 81.5% of entries and 29.1% of presentations. A head circumference was available for 50.2% of children <2 years age who had anthropometry recorded. The introduction of an electronic anthropometry database has been successful with increasing rates of use over time, especially in outpatient clinics. Further focus to improve inpatient recording of height and weight is needed.


Rhabdomyolysis resulting in concurrent Horner's syndrome and brachial plexopathy: a case report.
This case report describes a 29-year-old male who presented with immediate onset of Horner's syndrome and ipsilateral brachial plexopathy after sleeping with his arm dangling outside a car window for 8 h. Outside workup and imaging revealed rhabdomyolysis of the left neck musculature. Subsequent electrodiagnostic testing and high-resolution brachial plexus magnetic resonance imaging at the authors' institution attributed the Horner's syndrome and concurrent brachial plexopathy to rhabdomyolysis of the longus colli and scalene musculature, which had compressed-and consequently scar tethered-the cervical sympathetic trunk and brachial plexus. This case of co-existent Horner's syndrome and brachial plexopathy demonstrates the role of high-resolution brachial plexus MRI in diagnosing plexopathy and the importance of being familiar with plexus and paravertebral muscle anatomy.


Comparison of Feto-maternal Outcomes Among Various BMI Groups As Per Asia Pacific Standards: An Observational Retrospective Comparative Study in a Private Tertiary Care Center in Delhi.
To compare the feto-maternal outcomes among various BMI groups as per Asia Pacific Standards. This is a retrospective non-interventional observational study on 1396 antenatal women with singleton pregnancy. Their BMI based on pre-pregnancy weight was calculated and the women were divided into various groups as per Asia Pacific standards for BMI classification. Details of associated morbidities and delivery outcomes were noted in a pre-structured proforma and a comparison was made among the various groups using Chi square test. A p value of < 0.05 was taken as significant. Among the 1396 women under study, 10.6% were underweight, 36% had normal weight, 21% were overweight while 32% were obese or very obese. There was a significant association of low BMI with preterm labor (p value 0.03) and fetal growth restriction (p value < 0.01). Overweight and obese women were found to be more prone to hypertensive disorders of pregnancy (p value- 0.002), gestational diabetes (p value- 0.003) and overweight women were more prone to cholestasis of pregnancy (p value 0.03). The women with higher BMI had a significantly higher requirement of induction of labor (p value-0.0002). There was significant increased number of babies more than 90th percentile in overweight and obese women (p value 0.003). However, there was no change in Neonatal ICU admissions (p value 0.85) or neonatal mortality. Asia Pacific references should be used for studies related to all studies on BMI and pregnancy. All women having BMI outside the normal BMI spectrum are at increased risk of antenatal and postnatal complications. Early identification of such women will enable careful evaluation and counseling to improve the reproductive outcome and feto-maternal health.


The impact of structured decision making on absconding by forensic psychiatric patients: results from an A-B design study.
Few studies have investigated absconding from forensic hospitals and there are no published studies of interventions aimed at reducing these incidents in forensic settings. We present a study of the impact of a new policy using structured professional judgment and an interdisciplinary team-based approach to granting privileges to forensic patients. We assess the impact of this policy on the rate and type of absconding from a metropolitan forensic facility. Following concern about the rate of absconding at our hospital, a new policy was implemented to guide the process of granting hospital grounds and community access privileges. Employing an A-B design, we investigated the rate, characteristics, and motivations of absconding events in the 18 months prior to, and 18 months following, implementation of this policy to assess its effectiveness. Eighty-six patients were responsible for 188 incidents of absconding during the 42-month study window. The rate of absconding decreased progressively from 17.8% of all patients at risk prior to implementation of the new policy, to 13.8% during implementation, and further to 12.0% following implementation. There was a differential impact of the policy on absconding events, in that the greatest reduction was witnessed in absconsions occurring from unaccompanied passes; this was offset, to some extent, by an increase in absconding occurring from within hospital units or from staff accompanied outings. Seven of the absconding events included incidents of minor violence, and two included the commission of other illegal behaviors. The most common reported motive for absconding across the time periods studied was a sense of boredom or frustration. Discharge rate from hospital was 22.9% prior to the implementation of the policy to 22.7% after its introduction, indicating no change in the rate of patients' eventual community reintegration. A structured and team-based approach to decision making regarding hospital grounds and community access privileges appeared to reduce the overall rate of absconding without slowing community reintegration of forensic patients.


A novel flow-based strategy for implementing differential kinetic analysis.
Differential kinetic analysis can be implemented in a multi-pumping flow system, and this was demonstrated in relation to an improved spectrophotometric catalytic determination of iron and vanadium in Fe-V alloys. The method exploited the influence of Fe(II) and V(IV) on the rate of iodide oxidation by Cr(VI) under acidic conditions; therefore the Jones reductor was needed. The sample was inserted into an acidic KI stream that acted also as carrier stream, and a Cr(VI) solution was added by confluence. Successive measurements were performed during sample passage through the detector, each one related to a different yet reproducible condition for reaction development. Data treatment involved multivariate calibration by the PLS algorithm. The proposed system is very simple and rugged, allowing about 50 samples to be run per hour, meaning 48 mg KI per determination. The first two latent variables carry ca. 94% of the analytical information, pointing out that the intrinsic dimensionality of the data set is two. Results are in agreement with inductively coupled argon plasma-optical emission spectrometry.


Implementation of Real-Time Assessment of Patient-Reported Outcomes in a Heart Failure Clinic: A Feasibility Study.
Patient-reported outcomes (PROs) quantify, from patients' perspectives, their symptoms, function, and quality of life. Our aim was to determine the feasibility of integrating PRO capture into routine clinical practice at a large heart failure (HF) clinic. We examined the practicality of PRO completion at the time of clinic visit, the time required to complete the selected instruments, the completion rate, and the feasibility of immediate PRO scoring and integration of the results into the electronic health record (EHR). We deployed a computer program to capture PROs (Kansas City Cardiomyopathy Questionnaire, Patient-Reported Outcomes Measurement Information System) on a portable computer platform at the time of a clinic visit. An automated algorithm identified patients scheduled for appointments at the HF clinic at registration, provided a portable tablet computer with which to complete the appropriate PRO instruments and then scored and immediately integrated the results in the patient's EHR. In a 12-month period, 862 unique patients completed 1,320 PRO assessments. The mean age of this cohort was 60.1 ± 16.3 years and 66% were male. The average time for PRO assessment was 6.7 minutes and the completion rate among eligible patients was 58%, with 91% of started assessments completed in full. These preliminary data support the feasibility of serial PRO assessment with real-time integration into the EHR in a large outpatient population of patients with HF. We identified critical steps that should enhance adoption of this approach by clinicians and render PRO results meaningful and actionable in routine clinical care.


Fibroepithelial polyp in a child.
Only 15 cases of fibroepithelial polyp in children have been reported in the world medical literature. Clinical differentiation between this tumor and a malignant ureteral tumor is difficult and often results in unnecessary nephrectomy. We report the sixteenth case of a child with fibroepithelial polyp of the ureter. The lesion was resected, and the kidney was preserved. Optimum treatment of this lesion mandates renal preservation in children. The rationale for this recommendation is explored.


NIR-Remote Selected Activation Gene Expression in Living Cells by Upconverting Microrods.
An NIR-controlled gene expression system based on upconverting rods (UCRs) is demonstrated. The UCRs can harvest the "biocompatible" NIR light and convert it into local UV light, resulting in cleavage of the photosensitive molecule (4-(hydroxymethyl)-3-nitrobenzoic acid, ONA) and on-demand release of gene carriers, thus realizing target gene expression at high spatial and temporal resolutions.


Two-peptide bacteriocin PlnEF causes cell membrane damage to Lactobacillus plantarum.
Biologically active, artificially synthesized two-peptide bacteriocin PlnEF was used to study its mode of action on sensitive bacteria Lactobacillus plantarum pl2. The data obtained showed that PlnEF induced membrane permeabilization, allowing for the efflux of electrolytes, which was evidenced by the increased extracellular conductivity, the dissipation of transmembrane electrical potential and pH gradient, and rapid intracellular ATP depletion after L. plantarum pl2 cells were treated with PlnEF for minutes. Laser confocal microscopy showed that PlnEF accumulated very quickly in L. plantarum pl2 cells and the accumulation of PlnEF caused damage to cell membrane. Scanning electron microscopy and transmission electron microscopy further showed that PlnEF induced morphological changes and structure disruption to L. plantarum pl2 cells, such as the formation of blebs, microspheres, membrane deformation and cell lysis. In summary, the data obtained show that PlnEF caused cell membrane damage to L. plantarum pl2 cells. Our study reveals the antimicrobial mechanism of two-peptide bacteriocin PlnEF against L. plantarum.


Determination of selenium in drugs by oxygen flask combustion and ion chromatography.
A method is described for the determination of trace selenium (impurities in medicinal organic compounds) by ion chromatography (IC) after oxygen flask combustion. All selenium compounds formed by oxygen flask combustion are converted to selenate ion by heating with nitric acid and potassium permanganate. The selenate ion is then determined by IC, using a simple recycle system to eliminate interfering ions. The detection limit of selenium is 0.4 nmol in 50 mg of sample. The recoveries of selenium added to seven drugs are ca. 95-103% with relative standard deviations of 1-6%.


Lung cancer radiation therapy in Australia and New Zealand: Patterns of practice.
The RANZCR Faculty of Radiation Oncology Lung Interest Cooperative (FROLIC) surveyed patterns of lung cancer radiation therapy practice for non-small cell (NSCLC) and small cell lung cancer (SCLC) to evaluate current patterns of care and potential for improvement. In October 2014, Radiation Oncologists (ROs) from all 62 departments in Australia and New Zealand were invited to a web-based survey directed at those treating lung cancer. Questions covered current radiation therapy practice as well as quality measures. Fifty-eight per cent of respondents used 4D-CT simulation. For curative treatment, 98% employed 3D-CRT and 34% intensity modulated radiotherapy (IMRT) techniques. Treatment verification was primarily performed using cone-beam CT (86%). In NSCLC, the commonest curative dose-fractionation regime was 60 Gy/30# (96%) and for palliative intent, 30 Gy/10# (76%). Forty-four per cent treated patients with stereotactic ablative body radiotherapy (SABR) and half treated central tumours with this technique. In fit patients with synchronous solitary brain metastases, 80% would give radical treatment. For curative-intent SCLC, 45-50.4 Gy/25-28# (61%) and 45 Gy/30#/1.5 Gy b.d. (48%) were used. Ninety-four per cent discussed lung cancer patients at multidisciplinary meetings. Contours were peer-reviewed by 74% and 50% for conventional fractionation and SABR respectively. A significant proportion of ROs did not have access to 4D-CT. The majority used 3D image verification and consistently prescribed evidence based doses. A significant number did not participate in peer-review of contours. Practice in IMRT and synchronous oligo-metastatic disease is variable and should be an area of future research. Utilising survey findings, FROLIC is developing consensus recommendations to guide practice.


Multimodal Nutritional Management in Primary Lumbar Spine Surgery: A Randomized Controlled Trial.
A prospective randomized controlled trial. The purpose of this study was to evaluate the clinical effect and safety of a new multimodal nutritional management (MNM) protocol for patients receiving primary lumbar spine surgery. Poor nutritional status is common in the perioperative period in primary lumbar spine surgery, and may impede recovery after surgery. A total of 187 patients were included in this prospective randomized controlled trial. They were randomly assigned to the MNM group or the control group. Albumin (ALB) infusion, postoperative ALB level, electrolyte disorders, postoperative electrolyte levels, transfusion rate, postoperative hemoglobin level, length of stay (LOS), and complications were compared between the groups. Compared with the control group, the rate and the total amount of ALB infusion were lower in the MNM group, and the postoperative level of ALB in the MNM group was higher on the first postoperative day, and the third postoperative day. The incidence of hypokalemia, hyponatremia, and hypocalcemia were lower in the MNM group. In the MNM group, the postoperative levels of sodium, potassium, and calcium were higher than the control group. The transfusion rate was similar between the two groups. The hemoglobin level was similar between the two groups on first postoperative day, but was higher in the MNM group on third postoperative day. LOS in the MNM group was shorter than in the control group. The incidence of wound drainage was lower in the MNM group. No statistical differences were observed regarding surgical complications between the two groups. The MNM protocol effectively reduced ALB infusion, the incidence of electrolyte disorders, and wound drainage, increased the postoperative levels of ALB, sodium, potassium, and calcium, and reduced the LOS without increasing the rate of postoperative complications. 2.


Comparative inhalation toxicity of nickel sulfate to F344/N rats and B6C3F1 mice exposed for twelve days.
Groups of F344/N rats and B6C3F1 mice were exposed to aerosols of nickel sulfate hexahydrate (NiSO4.6H2O) 6 hr/day for 12 days to determine the short-term inhalation toxicity of this compound. Target exposure concentrations were 60, 30, 15, 7, 3.5, and 0 mg NiSO4.6H2O/m3. Endpoints evaluated included clinical signs, mortality, quantities of Ni in selected tissues, effect on mouse resistance to tumor cells, and pathological changes in tissues of both rats and mice. All mice exposed to 7 mg NiSO4.6H2O/m3 or greater and 10 rats exposed to 15 mg NiSO4.6H2O/m3 or greater died before the termination of exposures. Quantities of Ni remaining in lungs of rats at the end of the exposure were independent of exposure concentration. Lung burdens of Ni in mice were approximately one-half that in lungs of rats. Exposure of female mice to 3.5 mg NiSO4.6H2O/m3 had no effect on resistance to tumor cells as determined by spleen natural killer cell activity. Histopathological changes were seen in tissues of rats and mice exposed to as low as 3.5 mg NiSO4.6H2O/m3. Lesions related to NiSO4.6H2O exposure occurred in lung, nose, and bronchial and mediastinal lymph nodes. Results indicated that exposure of rats and mice to amounts of NiSO4.6H2O aerosols resulting in Ni exposure concentrations only eight times greater than the current threshold limit value for soluble Ni (0.1 mg/m3) for as little as 12 days can cause significant lesions of the respiratory tract.


Predictors of Mortality in HPV-Associated Oropharynx Carcinoma Treated With Surgery Alone.
Survival outcomes for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treated with surgery alone are unclear. To increase understanding, we assessed overall survival (OS) outcomes using the national cancer database (NCDB). We conducted a retrospective analysis of OS of 736 NCDB HPV + OPSCC patients who underwent surgery alone from 2010 to 2014 using univariate and multivariate analyses and the Kaplan-Meir method. Multivariable analysis found the following independent risk factors for death: American Joint Commission on Cancer (AJCC) 8th edition pathologic stage(p)N2 versus pN0 disease (hazard ratio [HR], 5.5; P = 0.000006), macroscopic extranodal extension (ENE) versus non-ENE (HR, 4.9; P < 0.02), a positive lymph nodes (LN) percentage of ≥10% (HR, 4.2; P = 0.0002), and five or more positive LNs (HR, 4.9; P = 0.00004). Three-year OS was significantly worse for AJCC 8th edition pN2 versus pN0 but not for 7th edition pN2 versus pN0 disease. Five-year OS was significantly worse for positive versus negative surgical margins, AJCC 8th edition stage II versus I, and either microscopic or macroscopic ENE versus non-ENE positive LNs. For 523 (71%) AJCC 8th edition stage I patients and for 283 (38%) patients who were pT1-T2, with negative margins, pN0-N1, with ≤4 pathologic LNs, without ENE, and with >20 LNs removed during neck dissection, the 3-year OS rates were 93% and 95%, respectively, and the 5-year OS rates were 91% and 95%, respectively. In the context of the lack of detail and possible inaccuracies found in the NCDB, surgery alone for AJCC 8th edition stage I HPV + OPSCC, particularly pT1-T2, pN0-N1 with ≤4 pathologic LNs, without ENE, and with negative surgical margins has a high OS. 4 Laryngoscope, 130:E423-E435, 2020.


Changes in distribution of platelet membrane glycoproteins in patients with myeloproliferative disorders.
Glycoproteins have been discovered to be important to platelet function both in normal and pathological states. We have studied membrane glycoprotein patterns in 16 patients with various myeloproliferative disorders. There was an abnormal ratio of glycoprotein I:glycoprotein IV in patients with myeloproliferative disease compared with controls. There was no discernible correlation between glycoprotein pattern and aggregation response or platelet count, but patients with megathrombocytes had higher values for glycoprotein IV than those without megathrombocytes. These experiments suggest that patients with myeloproliferative disorders may have alterations in membrane glycoproteins that could alter platelet function.


Economic burden of illness for employees with painful conditions.
We sought to compare the medical services utilization and average annual direct (ie, medical and medication) and indirect (ie, work-loss) costs for employees with painful conditions to a random sample ("average employee"). An employer administrative claims database (approximately 600,000 insured lives) was used to identify patients with ICD-9 codes for painful conditions. Direct costs were total employer medical and medication costs and indirect costs were associated with medically related absenteeism days and disability claims. Among employees with painful conditions, total costs were 1.5 to 3.5 times as high (P < 0.01) as those of the average employee (ie, 7088 US dollars to 16,874 US dollars compared with 4,849 US dollars) depending on the painful condition. Painful conditions are costly to employers, and better management/treatment of such conditions may help reduce the associated employer economic burden.


Modulation of the Bioactive Conformation of Transforming Growth Factor β: Possible Implications of Cation Binding for Biological Function.
In any organism, very precisely adjusted interaction and exchange of information between cellsis continuously required. These cooperative interactions involve numerous cytokines, acting throughcorresponding sets of cell-surface receptors. The transforming growth factor β (TGF-β)superfamily includes a variety of structurally related multifunctional cytokines that play criticalroles in maintaining cellular homeostasis and controlling cell fate. Response of a cell to a specificsignal it receives should depend upon the current state of the environment, including concentrationsof biologically relevant ions. One of the most biologically active ions, calcium, acts upon a specificcalcium signaling system that operates over a wide temporal range and regulates many cellularprocesses in continuous "cross-talk" with the TGF-β signaling system. In additionto that, the structural and dynamical properties of TGF-β molecules, along with detected directinteraction of them with the biologically relevant cations suggest another level of fine regulationof TGF-β activity. The fact that both mono- and divalent cations bind in the same low-affinitysites implies that some competition of cations for interaction with TGF-β can also occur in vivo,contributing to the diversity of TGF-β biological functions.


Prevalence of the C282Y and H63D mutations in the HFE gene in patients with hereditary haemochromatosis and in control subjects from Northern Germany.
Mutation analysis was performed for two HFE mutations (C282Y, H63D) in unrelated patients with hereditary haemochromatosis (n = 92), family members of patients (n = 34), and unrelated controls (n = 157) from Northern Germany, 87/92 patients (94.6%) revealed the C282Y mutation in homozygous form, five were heterozygous. No H63D mutation was found in 174 chromosomes of patients homozygous for C282Y, whereas four of the heterozygote patients also carried the H63D mutation. Among the control group, 9.6% were heterozygotes for C282Y. 2/157 subjects were homozygous, 37/157 were heterozygous for the H63D mutation, but showed no signs of iron overload.


Corticosterone levels in host and parasite nestlings: is brood parasitism a hormonal stressor?
Parasite chicks from non-evictor species usually try to monopolize host parental care, thereby increasing considerably the level of food competition in the nest. Here, we propose that brood parasitism is an important stressor for host and parasite nestlings and explore this hypothesis in the non-evictor great spotted cuckoo (Clamator glandarius) and its main hosts, the same-sized black-billed magpie (Pica pica) and the larger carrion crow (Corvus corone). We experimentally created 3-nestling broods of different brood compositions (only cuckoo chicks, only host chicks, or cuckoo and host chicks together) and measured baseline corticosterone levels of nestlings along their developmental period (early, middle and late). We found that brood parasitism increased corticosterone levels in magpie nestlings in the mid and late nestling period compared to those raised in unparasitized nests. Interestingly, carrion crow nestlings from parasitized nests only increased their corticosterone levels in the mid nestling period, when the competition for food with the cuckoo nestling was highest. Our results suggest that brood parasitism could be a potential physiological stressor for host nestlings, especially during the developmental stages where food requirements are highest. Conversely, cuckoo nestlings could be physiologically adapted to high competition levels since they did not show significant differences in corticosterone levels in relation to brood composition.


Nuclear localization of fructose 1,6-bisphosphatase in smooth muscle cells.
Fructose 1,6-bisphosphatase (FBPase)--a key enzyme of gluconeogenesis--for a long time was regarded to be soluble, and freely diffused in the cytoplasm. Our recent investigation revealed however, that in skeletal muscles of mammals, FBPase is located on both sides of the Z-line and, in cardiomyocytes, it is also present inside the cells' nuclei. In the current paper we demonstrate that, in smooth muscle cells, FBPase is located in the cytoplasm and the nucleus, and that the presence of the enzyme in the nucleus is almost completely restricted to the heterochromatin area. In search for additional evidence for the nuclear localization of FBPase and for a possible explanation of its role in the nucleus, we have analyzed the primary structures of muscle FBPases, finding on their molecular surface a number of domains specific for proteins transported into the nucleus.


Prevalence of Low-Calorie Sweeteners and Related Front-of-Package Claims in the Brazilian Packaged Food Supply.
Low-calorie sweeteners (LCSs) are increasingly being used worldwide, including in foods and beverages commonly consumed by children. To examine the prevalence of LCSs in packaged foods and beverages sold in Brazil, whether LCSs are added to products with advertising directed to children, and whether foods and beverages with LCSs include front-of-package (FoP) LCS-related health and nutrition claims. Cross-sectional study. A sample (n = 11,434) of packaged foods and beverages sold by the top 5 largest Brazilian food retailers was examined to identify LCSs and added sugars, and a subsample (n = 3491) was examined to determine the presence of advertising directed to children and FoP LCS-related claims in foods and beverages with LCSs. The prevalence of foods and beverages with different types of LCSs in the Brazilian food supply, among ultra-processed foods and beverages and among foods and beverages with added sugars, were measured. Foods and beverages with advertising directed to children were checked to see if these products had LCSs and how many products with LCSs had FoP labels with LCS-related claims. Mean and 95% CIs were used to determine the overall prevalence of foods and beverages with LCSs and in the different assessed stratifications. The prevalence of LCSs was 9.3% (95% CI 8.8-9.9) in Brazilian packaged foods and beverages, 14.6% (95% CI 13.8-15.4) in ultra-processed products alone, and 5.7% (95% CI 4.2-7.7) in foods and beverages with advertising directed to children. About 83% of food and beverage with LCSs were also sweetened with added sugars. LCSs were most frequently added to nonalcoholic sweetened beverages, breakfast cereals, and granola bars. Forty percent of foods and beverages with LCS did not present any FoP LCS-related claim. This study shows that LCSs are present in 15% of ultra-processed foods and beverages in Brazil, largely used in combination with added sugars, and are found in foods and beverages with advertising directed to children. Clearer FoP information regarding the presence of LCSs, in particular in products with advertising directed to children, can help consumers make more informed choices regarding LCS consumption.