Application of chemometrics using direct spectroscopic methods as a QC tool in pharmaceutical industry and their validation.
This present review described the application of chemometrics using direct spectroscopic methods at the quality control (QC) laboratory of Pharmaceutical Industries. Using chemometrics methods, all QC assessments during the fabrication processes of the drug preparations can be well performed. Chemometrics methods have some advantages compared to the conventional methods, i.e., non-destructive, can be performed directly to intake samples without any extractions, unnecessary performing stability studies, and cost-effective. To achieve reliable results of analyses, all methods must be validated first prior to routine applications. According to the current Pharmacopeia, the validation parameters are specificity/selectivity, accuracy, repeatability, intermediate precision, range, detection limit, quantification limit and robustness. These validation data must meet the acceptance criteria, that have been described by the analytical target profile (ATP) of the drug preparations.


Self-reports of eating quickly are related to a decreased number of chews until first swallow, total number of chews, and total duration of chewing in young people.
The validity of a self-questionnaire about eating quickly remains unclear. If a significant relationship between subjective and objective methods to evaluate eating quickly can be confirmed, then the subjective method can be widely and reliably used in many fields. This study investigated relationships between subjective and objective methods to evaluate eating quickly and also numerically characterized the kinesis of eating quickly in young people. One hundred and thirteen students (44 males and 69 females; mean age 22.8 ± 2.0 years) were selected. All subjects completed written questionnaires, and number of chews until first swallow, total duration of chewing, number of chews, chewing rate and bite size were measured using test products (a Japanese cracker and rice ball). Both male and female subjects who reported eating quickly showed a significantly lower number of chews until first swallow (Japanese cracker), a lower number of chews overall (rice ball), and a shorter total duration of chewing (rice ball) than other subjects. There was no difference in chewing rate between subjects who ate quickly or not. These findings suggest that using test products, self-reports of eating quickly are related to a decreased number of chews until first swallow, total number of chews, and total duration of chewing, but not chewing rate, and that a self-reported questionnaire to evaluate eating rate is valid in young people.


Lead-Free Highly Efficient Blue-Emitting Cs3 Cu2 I5 with 0D Electronic Structure.
Halide perovskites, including CsPbX3 (X = Cl, Br, I), have gained much attention in the field of optoelectronics. However, the toxicity of Pb and the low photoluminescence quantum yield (PLQY) of these perovskites hamper their use. In this work, new halide materials that meet the requirements of: (i) nontoxicity, (ii) high PLQY, and (iii) ease of fabrication of thin films via the solution process are explored. In particular, copper(I) halide compounds with low-dimensional electronic structures are considered. Cs3 Cu2 I5 has a 0D photoactive site and exhibits blue emission (≈445 nm) with very high PLQYs of ≈90 and ≈60% for single crystals and thin films, respectively. The large exciton binding energy of ≈490 meV explains well the 0D electronic nature of Cs3 Cu2 I5 . Blue electroluminescence of Pb-free halides is demonstrated using solution-derived Cs3 Cu2 I5 thin films.


Tumor suppressor microRNAs: Targeted molecules and signaling pathways in breast cancer.
Breast cancer is the most common type of cancer in women whose prevalence is increasing every year. Common strategies for diagnosis, prognosis and specific treatment of breast cancer need improvements to increase patients' survival. For this reason, there is growing number of efforts world-wide with molecular approaches. With the advent of microRNAs (miRNAs), they have been interested for almost all aspects of tumorgenesis and correlation of breast cancer and microRNAs was discovered for the first time in 2005. MiRNAs form a group of small noncoding RNAs which participate in regulation of gene expression and subsequently several biological processes and pathogenesis of various diseases. As other cancers, miRNAs involved in breast cancer are classified in two groups: the first group is tumor inducing miRNAs (also called oncomirs) that can induce tumor initiation and progression, and their expression is increased in cancerous cells. The second group is tumor suppressor miRNAs. In normal situation, tumor suppressor miRNAs prevent beginning and progression of breast cancer through suppressing the expression of various oncogenes. In this review we will give a general overview about miRNAs and breast cancer, and in the following, more discussion about tumor suppressor miRNAs, with focus on the best known of them and their targeted oncogenes and signaling pathways. Finally, we will point to application of this group of miRNAs in diagnosis, prognosis and treatment of patients.


Polish consumer categorisation of grilled beef at 6 mm and 25 mm thickness into quality grades, based on Meat Standards Australia methodology.
Meat Standards Australia (MSA) methodology was used to evaluate the sensory categorization of beef by Polish consumers. A significant quality range was created by utilisation of 3 muscles, M. psoas major, M. longissimus thoracis et lumborum, and M. semimembranosus from 22 divergent bull carcasses (Holstein-Friesian crosses with Limousine, Hereford). Consumers evaluated every sample for selected sensory traits and chose a grade. A trend was observed for 6 mm preparation to reduce the proportion of unsatisfactory SM, with a consequent increase in 3star counts, in contrast to reducing the proportion of PM 5star and LTL 4star with an increase in the lower categories. Within each thickness Polish consumers clearly distinguished between grades, defined by MQ4 (Meat Quality, 4 variables) boundaries derived from discriminant analysis. Similar accuracy was achieved for both thicknesses. It was concluded that the MQ4 score could be successfully used to support a meat quality grading system in Poland.


Dependence of blood levels of HSP70 and HSP90 on genotypes of HSP70, GSTT1, and GSTM1 gene polymorphism in individuals chronically exposed to mercury.
The relationship between blood levels of HSP72, HSP72+HSP73, and HSP90 and genotypes of three polymorphisms of the HSP70 family, HSPA1L (2437T/C) and HSPA1B (2074G/C and 1267A/G) as well as GSTT1 and GSTM1 polymorphisms was studied in 82 men chronically exposed to mercury. Of these, 40 men were exposed to mercury for more than 10 years (group 1) and 42 developed chronic mercuric intoxication (group 2). The groups differed significantly by TT (p=0.004) and TC (p=0.007) genotypes of HSPA1L gene locus 2437T/C. Differences in the heat shock protein content associated with HSP70 gene polymorphism were detected only for HSPA1B gene locus 2074G/C and consisted in reduction of HSP90 (p=0.020) and HSP72 (p=0.056) for GG genotype in group 2 in comparison with group 1. Combination of GSTT1(+)/GSTM1(0/0) genotypes was associated with reduction of the protein levels, while variants including GSTT1(0/0) were associated with a significant elevation thereof.


[Genetic study of plasmid integration into yeast chromosomes. VI. Patterns of the destabilization of chimeric chromosomes and their use in gene mapping].
The 2 microns DNA-dependent destabilization of yeast chimeric chromosomes III, IV, V was analysed. The comparison of its peculiarities with the earlier localized sites of episomal plasmid integration allowed to derive genetic regularities of destabilization process. Two destabilization rules that describe patterns of the loss of genetic information in the chromosome were formulated. The usefulness of this for mitotic intrachromosomal gene mapping in yeast was demonstrated using plasmid integration site mapping in chromosome I.


[Subpopulations of TIL in renal cell carcinoma and their clinical significance].
To study the relationship between tumor-infiltrating lymphocytes (TIL) and the prognosis of patients with renal cell carcinoma. Immunohistological chemistry method was employed to semiquantitatively assess the expression of TIL and its subpopulations. The prognostic values of various TIL subpopulations were also evaluated. T-lymphocyte was the main component of TIL, B-lymphocyte, monocyte, and nature killer (NK) cells were also presented but in relatively small numbers. T-lymphocyte was strongly correlated to the survival probability, but this correlation was not observed between the host survival and TIL or other subpopulations. T-lymphocyte can represent the host immunological status and can be used to judge the prognosis of patients with renal cell carcinoma.


The challenges of lifelong learning in biological and artificial systems.
How do biological systems learn continuously throughout their lifespans, adapting to change while retaining old knowledge, and how can these principles be applied to artificial learning systems? In this Forum article we outline challenges and strategies of 'lifelong learning' in biological and artificial systems, and argue that a collaborative study of each system's failure modes can benefit both.


Real-time patient weight monitoring system for chair based renal dialysis.
A system is described for monitoring weight changes in patients undergoing renal dialysis. Relatively fit patients dialyse in easy chairs rather than in bed but no commercial system is currently available to monitor weight changes under these conditions. The authors have considered basic requirements and have developed a cost effective system based on a Single Point Off-Centre load cell, all components being mounted under a platform on which the easy chair is located. There is an electrical output signal which may be used to drive a display or be sampled by a computer system.


Exploring Leeuwenhoek's legacy: the abundance and diversity of protozoa.
Towards the end of the 17th century, Leeuwenhoek built "magnifying glasses" that enabled him to see and describe protozoa for the first time. Continued exploration of the natural history of protozoa during the past 300 years has progressed far beyond simply documenting morphospecies (global total probably <20,000). We now realize that protozoan 'biodiversity' is multi-faceted (e.g. sibling species, variant genotypes and syntrophic consortia). Realization of their extraordinary abundance has secured for protozoa the position of dominant phagotrophs and regenerators of nutrients within microbial food webs. And studies of protozoa in the natural environment have done much to effect a paradigm shift in our understanding of why specific microbes live where they do and how they got there in the first place. In particular, the hypothesis of ubiquitous dispersal of protozoan species does seem to be supported by the evidence provided by morphospecies, sibling species and even individual genotypes.


Relationship between lymphocytic cytotoxicity and phytohemagglutinin-induced lymphoblastogenesis before and after surgical tumor excision: an experimental study.
Experimental study was performed on changes in lymphocytic cytotoxicity and phytohemagglutinin (PHA)-lymphoblastogenesis after surgical tumor excision and on a possibility of estimating antitumor immunocompetence based on the latter parameter, using 3-methyl-cholanthrene-induced mammary cancer, MRMT-1, of SD rats. When the tumor was excised at 2 weeks after inoculation, cytotoxicity showed, after a transient rise, a marked reduction at 4 weeks postoperatively in the cases of postoperative negative metastasis, while it showed a high peak at 3 weeks postoperatively, followed by a sharp descent, in the cases of postoperative positive metastasis. On the other hand, PHA-lymphoblastogenesis was found to recover a relatively high level postoperatively, in the cases of both negative and positive metastases. It appears to be difficult to estimate specific cytotoxicity from PHA-blastogenesis, but both are useful, in complementary fashion, to estimate the antitumor immunocompetence.


Surgical Strategy and Outcomes of Full Endoscopic Lumbar Discectomy for Recurrent Lumbar Disk Herniation Following a Previous Full Endoscopic Lumbar Discectomy.
Recurrent lumbar disc herniation (RLDH) cannot be prevented after full endoscopic lumbar discectomy (FELD), and the optimal surgical treatment for RLDH after FELD remains controversial. The aim of the study was to suggest a surgical strategy for FELD to treat RLDH following a previous FELD and to present surgical outcomes. Between February 2015 and March 2022, 68 patients with RLDH were surgically treated with FELD retrospectively. An original approach was suggested for the treatment of early recurrence (24 h-2 weeks). The full endoscopic transforaminal technique (FETD) was considered for patients requiring local anesthesia, and in RLDH with FETD indications or FEID technological difficulties. The full endoscopic interlaminar technique (FEID) was chosen in RLDH with FEID indications. Both FEID and FETD were suitable if no FEID or FETD technological difficulties existed. Clinical efficacy was evaluated using the visual analog scale (VAS) score, Oswestry disability index (ODI), and modified MacNab criteria. Postoperative follow-up data at 24 h, 3 months, and final-follow-up were recorded. Operation time and clinical outcomes were assessed with t test. p-value < 0.05 was considered statistically significant. All 68 patients had an average follow-up time of 23.8 months (range, 6-76 months). In the 13 cases of early recurrence, the operation time (32.30 ± 9.67 vs. 58.00 ± 6.16 min) in the original surgical approach group was shorter than that in the changing surgical approach group (p < 0.05). In the 28 cases of L4/5 FETD recurrence (>2 weeks), the operation time (66.17 ± 12.18 vs. 53.60 ± 5.45 min) in the FETD group was more than that in the FEID group (p < 0.05). In the 22 cases of L5S1 recurrence (>2 weeks), the operation time (55.75 ± 8.79 vs. 79.33 ± 6.65 min) in the FEID group was shorter than in the FETD group (p < 0.05). The postoperative VAS and ODI scores at 24 h, 3 months, and final-follow up were all significantly improved, compared with their preoperative counterparts (p < 0.05). Based on the modified MacNab criteria, 88.23% of patients showed excellent or good results. Re-recurrence occurred in three patients at 3 months. No surgical complications were observed in any of the 68 cases. FELD is a safe and effective treatment option for RLDH with previous FELD. For early recurrence, the original approach was suggested. Both FEID and FETD were effective and safe for recurrence (>2 weeks), but FEID seemed more efficient for L4/5 RLDH after previous FETD and for L5S1 RLDH.


Bone alterations in children and young adults with renal transplant assessed by phalangeal quantitative ultrasound.
Bone alterations in young renal transplant recipients were investigated in several studies with conflicting results. Quantitative ultrasound of the phalanges is a recently developed noninvasive procedure to assess skeletal status. Cross-sectional study at a single transplant center with values compared with previously studied healthy controls. 40 children and young adult recipients of renal grafts (15 females, 25 males; age, 20.0 +/- 8.4 years) studied 7.1 +/- 3.8 years after kidney transplantation. Clinical, biochemical, and therapeutic features, including calcium, phosphate, and intact parathormone levels; and cumulative dosages of glucocorticoids and cyclosporine administered since transplantation. Phalangeal quantitative ultrasound, including amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT), mainly dependent on mineral density and cortical thickness, respectively. Age- and sex-matched healthy controls were used to provide age-related z scores; sex- and height-matched healthy subjects, to provide z scores related to statural age. Mean z scores of AD-SoS and BTT were -0.05 +/- 1.59 and -0.54 +/- 1.17, respectively (P > 0.05 and P < 0.001, respectively). Multivariate analysis showed that AD-SoS z score was associated significantly with body mass index, intact parathormone level, cumulative glucocorticoids administered in the first posttransplantation year, and cyclosporine administered since transplantation (model r(2) = 0.79; P < 0.001); BTT z score was associated significantly with glucocorticoid dosage in the first posttransplantation year and age (model r(2) = 0.55; P < 0.001). Absence of other measures of bone structure and longitudinal measures and comparison to a noncurrent control group. Children and young adults may have decreased cortical thickness with maintained overall mineral density after renal transplantation. The findings of phalangeal quantitative ultrasound parallel observations using other imaging techniques. Phalangeal quantitative ultrasound may be a useful method to assess bone alternations after renal transplantation.


PBDE-47 and PBDE mixture (DE-71) toxicities and liver transcriptomic changes at PND 22 after in utero/postnatal exposure in the rat.
Pentabromodiphenyl ethers (PBDE) are found in human tissue, in household dust, and in the environment, and a particular concern is the potential for the induction of cancer pathways from these fat-soluble persistent organic pollutants. Only one PBDE cancer study has been conducted and that was for a PBDE mixture (DE-71). Because it is not feasible to test all PBDE congeners in the environment for cancer potential, it is important to develop a set of biological endpoints that can be used in short-term toxicity studies to predict disease outcome after long-term exposures. In this study, PBDE-47 was selected as the test PBDE congener to evaluate and compare toxicity to that of the carcinogenic PBDE mixture. The toxicities of PBDE-47 and the PBDE mixture were evaluated at PND 22 in Wistar Han rat (Crl: WI (Han)) pups after in utero/postnatal exposure (0, 0.1, 15, or 50 mg/kg; dams, GD6-21; pups, PND 12-PND 21; oral gavage daily dosing). By PND 22, PBDE-47 caused centrilobular hypertrophy and fatty change in liver, and reduced serum thyroxin (T4) levels; similar effects were also observed after PBDE mixture exposure. Transcriptomic changes in the liver included induction of cytochrome p450 transcripts and up-regulation of Nrf2 antioxidant pathway transcripts and ABC membrane transport transcripts. Decreases in other transport transcripts (ABCG5 & 8) provided a plausible mechanism for lipid accumulation, characterized by a treatment-related liver fatty change after PBDE-47 and PBDE mixture exposure. The benchmark dose calculation based on liver transcriptomic data was generally lower for PBDE-47 than for the PBDE mixture. The up-regulation of the Nrf2 antioxidant pathway and changes in metabolic transcripts after PBDE-47 and PBDE mixture exposure suggest that PBDE-47, like the PBDE mixture (NTP 2016, TR 589), could be a liver toxin/carcinogen after long-term exposure.


Involvement of coated vesicles in the initiation of fast axonal transport.
The present study examines whether coated vesicles play a role in the intrasomal transit of newly synthesized fast-transported proteins. Coated vesicles isolated from bullfrog brain were shown to have a protein composition and ultrastructure similar to purified bovine brain coated vesicles. Bullfrog brain was then used as unlabeled carrier for the isolation of coated vesicles from dorsal root ganglia labeled with [3H]leucine. Fast-transported [35S]methionine-labeled proteins were generated in separate preparations from sciatic nerve, and co-electrophoresed on two-dimensional gels with [3H]proteins of the coated vesicle fraction. The [35S]Met fluorographic X-ray film pattern was used as a guide to remove gel regions which were tested for the presence of 3H. By this means, 45 of 67 individual fast-transported proteins examined were found to contain significant levels of 3H. The fact that these proteins have similar net charge and molecular weight characteristics to the mature fast-transported proteins with which they co-migrated, suggests that such species have already undergone post-translational modifications prior to becoming associated with coated vesicles. Since most modifications of this type occur in the Golgi apparatus, it appears that the majority of fast-transported proteins are isolated in association with a population of post-Golgi coated vesicles. The role of coated vesicles is incorporated into a model describing the pathway taken by fast-transported proteins during the initiation of fast axonal transport.


Risk factors associated with reduced work productivity among people with chronic knee pain.
To determine the burden and risk factors associated with reduced work productivity among people with chronic knee pain. A longitudinal study, nested within a randomised controlled trial (RCT) evaluating the long-term effects of dietary supplements, was conducted among people with chronic knee pain in paid employment (n = 360). Participants recorded days off work (absenteeism) and reduced productivity while at work (presenteeism) for seven days every two months over a 12-month period in a study specific diary. Examined risk factors included knee pain severity, occupational group, radiographic disease severity, physical activity, body mass index (BMI), health-related quality of life (SF-12) and co-morbidity. Over the 12-month follow up period, 50 (14%) participants reported one or more days off work due to knee problems, while 283 (79%) reported reduced productivity while at work (presenteeism <100%). In multivariate analysis, the only significant risk factor for absenteeism was having an SF-12 Mental Component Summary (MCS) score <40 (OR: 2.49 [95% CI: 1.03-5.98]). Significant risk factors for presenteeism included; reporting an; SF-12 Physical Component Summary (PCS) score <50 (OR: 1.99 [95% CI: 1.05-3.76]), semi-manual labour (OR: 2.23 [1.09-4.59]) or manual labour (OR: 6.40 [1.44-28.35]) or a high maximum knee pain (4-6 out of 10) (OR: 2.29 [1.17-4.46]). This longitudinal study found that among this cohort of people with chronic knee pain, the burden of reduced work productivity is mainly attributable to presenteeism rather absenteeism. This study demonstrated that effective strategies to increase work productivity should focus on reducing knee pain or physical disability especially among workers in manual or semi-manual labour.


Activity of gamma interferon in combination with pyrimethamine or clindamycin in treatment of murine toxoplasmosis.
The activity of recombinant gamma interferon (rIFN-gamma) in combination with either pyrimethamine or clindamycin was examined in a murine model of acute toxoplasmosis. Mice received either pyrimethamine or clindamycin alone or in combination with rIFN-gamma. Significantly increased survival and/or time to death was observed in animals treated with pyrimethamine or clindamycin in combination with rIFN-gamma compared to those that received treatment with any of the agents alone.


Functional characterization of an (R)-selective styrene monooxygenase from streptomyces sp. NRRL S-31.
Styrene monooxygenases (SMOs) are two-component enzymes known to catalyze the epoxidation of styrene to (S)-styrene oxide. In this work, we identified a new oxygenase component, named StStyA, from the genome of Streptomyces sp. NRRL S-31. StStyA displayed complementary stereoselectivity to all of the known SMOs when coupled with a known reductase component (PsStyB), which made it the first natural SMO that produces (R)-styrene oxide. Accordingly, a plasmid co-expressing StStyA and PsStyB was constructed, which led to an artificial two-component SMO, named StStyA/B. When applied in the bio-epoxidation of nine aromatic alkenes, the enzyme showed activity toward five alkenes, and consistently displayed (R)-selectivity. Excellent stereoselectivity was achieved for all five substrates with enantiomeric excesses ranging from 91% to >99%ee.


Salsolinol and isosalsolinol: condensation products of acetaldehyde and dopamine. Separation of their enantiomers in the presence of a large excess of dopamine.
Dopamine (DA) condenses, at least in vitro, with acetaldehyde, the primary metabolite of ethanol, to form the regioisomers salsolinol (SAL) and isosalsolinol (isoSAL). An alternative in vivo route to SAL, requiring a decarboxylation step, has been suggested via condensation of DA with pyruvic acid. SAL has been proposed as a mediator of the rewarding effects of ethanol in the brain. We have now shown by HPLC, nuclear magnetic resonance (NMR) and mass spectrometry (MS) that the commercially available SAL contains about 10% of isoSAL, whose biological activity is unknown. If SAL is indeed the biologically active metabolite, rather than isoSAL, it is also unknown whether the rewarding molecule is (S)- or (R)-SAL. We have developed methodologies for the quantitative determination of DA, SAL and isoSAL using ion-pair reversed-phase HPLC, and for the separation of DA from (S)- and (R)-SAL and an isoSAL enantiomer on a β-cyclodextrin-modified column, in both cases with electrochemical detection. A significant advance over earlier methods was achieved for the analysis of (S)- and (R)-SAL in the presence of a large excess of DA (100:1 DA-SAL ratio), as expected to occur in vivo, by suppressing the DA peak by selective derivatization with 2,3-naphthalenedicarboxaldehyde into a molecule that is electrochemically silent at the electrode potential used. The methodologies developed will allow the separation and determination of the pharmacological activity of these two products of condensation of acetaldehyde with DA. Further, the techniques for (S)- and (R)-SAL separation at a high DA:SA ratio will allow the existence of a putative (R)-SAL synthase to be determined and, if it exists, its role in alcoholism.


HLA class II antigens are associated with Japanese pemphigus patients.
We investigated the HLA class II antigens in 30 Japanese cases of pemphigus, 17 cases of pemphigus vulgaris (PV) and 13 cases of pemphigus foliaceus (PF), by both serologic and restriction fragment length polymorphism (RFLP) analyses. We detected two major haplotypes susceptible to PV, i.e., DRw12-DQw7 and DRw6-DQw5. In contrast, DR2 was absent in PV. RFLP analyses showed that DRw6 PV patients had a disease-associated restriction fragment representing DQw5, the same association as that found in DRw6 Jewish PV patients. However, DRw12 Japanese PV patients had DQw7, whereas DR4 Jewish PV patients had DQw8. On the other hand, all 13 PF patients were serologically typed for DQw1, which could not be further subdivided into DQw5 by RFLP analyses. These results suggest that Japanese and Jewish PV patients may be immunogenetically closely related to each other, but Japanese PV patients appear to be immunogenetically different from Japanese PF patients.


Sentence context influences the subjective perception of foreign accents.
We examined whether sentence context (the predictability of the final word) influences listeners' ratings of foreign-accented words. Previous work has demonstrated that accent manipulations affect listeners' processing of spoken language. We examined the converse of this relationship; whether context manipulations affect listeners' perceptions of accents. If there is a bidirectional relationship, listeners should be more likely to rate an accent as strong when the accented word is not predicted by the sentence. In Experiment 1, the results revealed that participants were significantly more likely to rate words spoken by foreign-accented speakers as "Strong Accent" in the unpredictable sentences when compared to the predictable sentences. Moreover, in Experiment 2, this effect was replicated and extended to a native speaker. These results support the idea that there is a bidirectional relationship between language processing and perceptions of accents. We discuss the practical implications for foreign-accented speakers.


Proteomic analysis of plasma proteins in diabetic retinopathy patients by two dimensional electrophoresis and MALDI-Tof-MS.
Diabetic retinopathy is a highly specific vascular complication of diabetes mellitus and progresses from mild non-proliferative abnormalities characterized by increased vascular permeability to moderate and severe proliferative diabetic retinopathy characterized by the growth of blood vessels on the retina. The aim of the study was to identify the differentially expressed proteins in diabetic retinopathy using two-dimensional electrophoresis. Blood sample was drawn from subjects with diabetes mellitus (without retinopathy) who served as controls and patients with diabetic retinopathy in tubes containing EDTA as anticoagulant. Albumin and immunoglobulin IgG collectively removed to enrich proteins of lower abundance. 2de was carried out to see if there are any differentially expressed proteins. Approximately 48 and 61 spots were identified in control and diabetic retinopathy respectively, of which three protein spots RBP1 (retinol-binding protein 1), NUD10 (Diphosphoinositol polyphosphohydrolase 3 alpha), NGB (neuroglobin) were down regulated and HBG2 (hemoglobin) and BY55 (CD 160 antigen) were upregulated in diabetic retinopathy. These five protein spots were excised and were subjected to in-gel tryptic digestion, and their identities were determined by ultraflex MALDI-TOF-MS. We report a comprehensive patient-based plasma proteomic approach to the identification of potential biomarkers for diabetic retinopathy screening and detection. We identified 5 different proteins that were differentially expressed in the plasma of control diabetic patients (without retinopathy). Among these five proteins the expression of neuroglobin (NGB) protein varied significantly and may be a potential biomarker in diabetic retinopathy.


Modelling behaviors relevant to brain disorders in the nonhuman primate: Are we there yet?
Recent years have seen a profound resurgence of activity with nonhuman primates (NHPs) to model human brain disorders. From marmosets to macaques, the study of NHP species offers a unique window into the function of primate-specific neural circuits that are impossible to examine in other models. Examining how these circuits manifest into the complex behaviors of primates, such as advanced cognitive and social functions, has provided enormous insights to date into the mechanisms underlying symptoms of numerous neurological and neuropsychiatric illnesses. With the recent optimization of modern techniques to manipulate and measure neural activity in vivo, such as optogenetics and calcium imaging, NHP research is more well-equipped than ever to probe the neural mechanisms underlying pathological behavior. However, methods for behavioral experimentation and analysis in NHPs have noticeably failed to keep pace with these advances. As behavior ultimately lies at the junction between preclinical findings and its translation to clinical outcomes for brain disorders, approaches to improve the integrity, reproducibility, and translatability of behavioral experiments in NHPs requires critical evaluation. In this review, we provide a unifying account of existing brain disorder models using NHPs, and provide insights into the present and emerging contributions of behavioral studies to the field.


Possible horizontal transmission of Salmonella via reusable egg trays in Thailand.
Salmonella contamination of eggshells, egg contents, reusable egg trays, and various environmental samples was assessed. Although the overall Salmonella contamination rate from egg farms was low (3.2%), over a quarter (26.7%) of egg trays from farms and more than one third (36.7%) of trays from the market were contaminated. Salmonella strains isolated from reusable egg trays were analyzed by serotyping, antimicrobial susceptibility test and XbaI pulsed-field gel electrophoresis (PFGE) typing. Five serovars (S. Braenderup, S. Emek, S. Weltevreden, S. Stanley, and S. Derby) were isolated, and half of the strains assessed were found to be resistant to one or more of the six antimicrobial agents examined. The overall resistance rates to nalidixic acid, trimethoprim-sulfamethoxazole, tetracycline, and ampicillin were 40.7%, 36.0%, 26.7% and 3.5%, respectively. The PFGE types were matched against sample location and drug resistance. S. Braenderup PFGE type A2 (susceptible to all tested drugs) was isolated from all sample sites; PFGE type A2 (resistant to nalidixic acid) was isolated from Farm C and the market. S. Braenderup PFGE type A1 (resistant to four drugs) was isolated from Farms A and C. S. Weltevreden PFGE type C3 (susceptible to all tested drugs) was isolated from Farms A and B and type C4 (susceptible to all tested drugs) was isolated from Farm A and the market. The distribution of the related genotypes and resistance patterns of Salmonella in egg farms and the market indicate drug-resistant strains of Salmonella may be spread on reusable egg trays.


Model-based signal tracking in the quantitative analysis of time series of NMR spectra.
Hard modeling of NMR spectra by Gauss-Lorentz peak models is an effective way for dimensionality reduction. In this manner high-dimensional measured data are reduced to low-dimensional information as peak centers, amplitudes or peak widths. For time series of spectra these parameters can be assumed to be smooth functions in time. We suggest to model these time-dependent parameter functions by cubic spline functions, which makes a stable quantitative analysis of NMR series possible even for crossing, highly overlapping peaks. Applications are presented for the batch distillation of methanol and diethylamine, and the reaction of acetic anhydride with 2-propanol.


Germanium-68 as a tracer for silicon fluxes in freshwater sediment.
The sorption of Si may decisively influence the P dynamics in surface sediment through competitive ligand exchange mechanisms. Many aspects of the process, such as the impact of Si dissolving from diatoms, are both insufficiently known and difficult to monitor by quantitative analyses due to the ubiquitousness of Si in sediment. Since the radioactive isotopes of Si have impractical half-times, the applicability of 68Ge as a tracer for Si additions in both inorganic and biogenic form to freshwater sediment (Lake Vesijärvi, Southern Finland) was studied in a 24-h laboratory experiment. The 68Ge-label was added to the sediment with either inorganic Si (940mg l(-1)) or diatoms (3.2 x 10(6) cellsl(-1)), and the distributions of the 68Ge-label and the different forms of added Si between the interstitial water and sequentially extracted, solid-phase sediment pools were critically examined. The inorganic Si addition significantly increased the amount of Si in the interstitial water and in the reversibly bound fraction, while the diatom addition had no discernible effects. The relative distribution of Si and 68Ge between the various sediment pools indicated that the first sorption phase of the added inorganic Si was similar to that reported for P. The high concentration of diatom-derived 68Ge-labelled Si in the interstitial water and in the easily soluble, reversibly bound pool indicated rapid dissolution of the added diatoms. The comparable distributions of the diatom-derived and inorganic Si-derived 68Ge-label within the studied pools indicated that the sorption of Si dissolving from diatoms in surface sediment closely resembles that of an inorganic addition of Si. Caution about the chemical speciation of the 68Ge-label is, however, advisable in sediment environments. Fractionation procedures designed for e.g. P may also be of limited use when applied to a different element, such as Si.


Elbow arthroscopy in children and adolescents: analysis of outcome and complications.
Chondral or osteochondral lesions, post-traumatic contracture and loose bodies of the elbow are often associated with chronic pain, stiffness, repetitive swelling and joint blockages. Therefore, arthroscopy of the elbow is often used in the elderly for the treatment of osteochondral defects or arthrolysis. There are only a few reports and studies about arthroscopic therapy of the elbow in children and adolescents. This study assesses the clinical outcome of arthroscopic therapy in this age group. In a retrospective study, children and adolescents who underwent an elbow arthroscopy in the period from 2010 to 2014 were included. The children were evaluated using the validated outcome measures Mayo Elbow Performance Score (MEPS), range of motion, pain on visual analog scale (VAS), Oxford Elbow Score (OES), quick dash and postoperative satisfaction. Furthermore, all complications were analyzed. In total, 27 patients were included. The mean (range) age was 14 (11-17) years, with a follow-up of 45 months. Fourteen (52%) were female and thirteen children (48%) were male. Twenty children had an arthroscopy due to osteochondritis dissecans and seven children for post-traumatic pain and stiffness. The mean (standard deviation) MEPS improved from 65 (15) to 96 (8; p = .005). The OES and quick dash were 93 and 5.4. The mean extension improved from - 15° (± 13.8) to 3° (± 10.2; p < .001). The mean flexion improved from 131° (± 13.4) to 137° (± 9.5; p = .003). Average pain on VAS was postoperative .2 (± .5), and 81.5% of all children had excellent or good results. There were no complications such as damage of nerves or blood vessels observed. Elbow arthroscopy is an appropriate and safe treatment option in children and adolescents with good and excellent postoperative results.


3D Printing of Clear Orthodontic Aligners: Where We Are and Where We Are Going.
Clear orthodontic aligners were developed at the end of the 1990s [...].


Mechanisms of in vitro immunosuppression by hepatocyte-generated cyclophosphamide metabolites and 4-hydroperoxycyclophosphamide.
Cyclophosphamide (CY) is metabolized to 4-hydroxy-CY which spontaneously breaks down to the reactive intermediates, phosphoramide mustard (PAM) and acrolein. The alkylating property of PAM is thought to mediate the anti-proliferative and cytotoxic actions of CY. Acrolein is known to bind sulfhydryl groups of cellular molecules and may contribute to the action of CY. However, the role of acrolein in the CY-induced immunosuppression remains unclear. The results of studies in which a hepatocyte co-culture system was used suggest that acrolein may play an important role in the cytotoxic action of CY, whereas those investigations using activated derivatives of CY indicate that acrolein is not an important factor. Thus, both approaches of CY exposure were utilized in the present study. Splenocytes of B6C3F1 mice were incubated with syngeneic isolated hepatocytes and CY or with 4-hydroperoxycyclophosphamide (4-HC) (which spontaneously decomposes to 4-hydroxy-CY). The in vitro antibody forming cell (AFC) response was found to be suppressed with both methods of exposure to CY metabolites. The addition of DNA to bind extracellular PAM was ineffective in preventing the suppression produced by hepatocyte-activated CY. However, it was also observed that DNA was able to attenuate the PAM-induced suppression. The sulfhydryl compounds 2-mercaptoethanesulfonate (MESNA) (15 microM) or reduced glutathione (GSH) (1 mM) inhibited the suppression of the AFC response of splenocytes incubated with CY and mouse hepatocytes. The suppression produced by 4-HC, however, was not affected by MESNA and only slightly inhibited by GSH. Similarly, the PAM-induced suppression was not affected by MESNA and slightly attenuated with GSH. In contrast, both MESNA and GSH were very effective in abrogating the acrolein-induced suppression, whereas DNA was ineffective. The findings of this study suggest that in the hepatocyte co-culture system, the immunosuppressive actions of CY are mediated by acrolein generated outside of the splenocyte, whereas the 4-HC induced suppression is not mediated by extracellular acrolein. Thus, this difference may explain the contradictory findings of previous studies that used different means of exposing cells to activated CY.


Local contamination is a major cause of early deep wound infections following open posterior lumbosacral fusions.
Postoperative surgical site infection in patients treated with lumbosacral fusion has usually been thought to be caused by perioperative contamination. With the proximity of these incisions to the perineum, this study sought to determine if contamination by gastrointestinal and/or urogenital flora should be considered as a major cause of this complication. We conducted a retrospective review of adults treated with open posterior lumbosacral fusions between 2014 and 2021 to identify common factors in deep postoperative infection and the nature of the infecting organisms. Cases of tumor, primary infection and minimally invasive surgery were excluded. 489 eligible patients were identified, 20 of which required debridement deep to the fascia (4.1%). Mean age, operative time, estimated blood loss and levels fused were similar between both groups. The infected group had a significantly higher BMI. The mean time from primary procedure to debridement was 40.8 days. Four patients showed no growth, 3 showed Staphylococcus sp. infection (Perioperative Inside-Out) requiring debridement at 63.5 days. Thirteen showed infection with intestinal or urogenital pathogens (Postoperative Outside-In) requiring debridement at 20.0 days. Postoperative Outside-In infections led to debridement 80.3 days earlier than Perioperative Inside-Out infections (p = 0.007). 65% of deep infections in patients undergoing open lumbosacral fusion were due to early contamination by pathogens associated with the gastrointestinal and/or urogenital tracts. These required earlier debridement than Staphylococcus sp. There should be renewed focus on keeping these pathogens away from the incision during the early stages of wound healing.


Simulation of NMR data from oriented membrane proteins: practical information for experimental design.
Several hundred solid state NMR dipolar couplings and chemical shift anisotropies were simulated for the polytopic membrane protein, bacteriorhodopsin, and for an idealized transmembrane peptide conforming to several different secondary structures (alpha- and 3(10)-helices and parallel and antiparallel beta-sheets), each at several tilt angles with respect to the bilayer normal. The use of macroscopically oriented samples was assumed. The results of these simulations suggest: (i) Because of the r-3 dependence of dipolar coupling, it is likely to prove difficult to successfully execute uniform isotopic enrichment strategies to generate large numbers of quantitatively interpretable structural measurements in oriented sample NMR studies of membrane proteins. (ii) There are a number of readily implementable specific isotopic labeling schemes which can yield data patterns sufficient to identify local secondary structure for transmembrane segments of idealized proteins which are tilted by < 10 degrees with respect to the bilayer normal. (iii) The measurement of dipolar coupling constants between 13C-, 19F-, and/or 3H-labeled side chains of proximal residues may prove effective as routes to long range tertiary structural data constraints.


Intersphincteric excision of the rectum.
Wide excision of the rectum in inflammatory bowel disease is both unnecessary and undesirable as the healthy pelvic floor is damaged and the pelvic nerves put at risk. An operative technique is described which includes dissection of the anal canal and rectum in the intersphincteric plane, i.e. the plane of fusion between the visceral rectum and anal canal and the somatic pelvic musculature, which minimizes these undesirable elements. Fifty-three cases are presented. Perineal wound healing rates are comparable with those of other methods of resection and only 1 of 14 men reported partial sexual dysfunction following this operation.


Pediatric trauma in the rural and low resourced communities.
Death and disability associated with traumatic injury can be significantly decreased with timely and appropriate care. Patients in rural areas tend to have disproportionately decreased access to this care, with the pediatric age group acting as a particularly difficult challenge for pre-hospital and rural hospital settings due to the unfamiliarity of those trauma response teams with pediatric age specific management guidelines as well as a disparity in resource availability. In this review, we attempt to discuss the challenges facing pediatric trauma care in the rural and low resourced communities, as well as initiatives that are being carried out to optimize this kind of care, such as pediatric readiness, rapid transportation to higher levels of care, availability of blood in rural centers as well as in transit, and the utility of telemedicine in improving rural pediatric trauma care.


Pesticide use among greenhouse workers in Turkey.
Pesticides are chemicals use of which has increased worldwide since the Second World War in order to improve the quality and the quantity of agricultural products. Their harmful effects on the environment and the human health have also been seen as usage increases. Although there have been studies about the harmful effects of pesticides on human health in the developing countries, there is limited data about the use of pesticides in Turkey. The aim of our study was to obtain data about the use of pesticides in greenhouse in Turkey. About 131 greenhouse workers were interviewed with within the province of Izmir: 63.8% graduated from primary school; 49.2% were living in region where the greenhouses were located; 46.2% were working in their own greenhouses; 42.3% had health insurance; 86.9% used pesticides and 59.3% did not take protective cautions during use pesticide. The application technique, location, amount, time or any other required information of the pesticides used have not been recorded by the greenhouse workers.


Myocardial imaging with 201thallium: an analysis of clinical usefulness based on Bayes' theorem.
Rest-exercise thallium-201 (201Tl) myocardial imaging and rest-exercise electrocardiography were performed in 137 patients with suspected coronary artery disease (CAD). The final diagnosis of coronary disease was made by arteriography. Sensitivity and specificity for the ECG and thallium studies alone or combined were then determined. Based on these data, the posttest probability of CAD with a normal or abnormal test was calculated using Bayes' theorem for disease prevalences ranging from 1%--99%. The difference between the probability of disease with a normal test and the probability of disease with an abnormal test was also calculated for each prevalence range. The results demonstrate that 201Tl imaging discriminates between disease absence or presence better than does the ECG. However, both the ECG and thallium studies provide rather poor discrimination between disease and no disease when the disease prevalence is low (less than 0.20) or high (greater than 0.70). Because of this characteristic, it is unlikely that screening tests for CAD will prove useful unless the disease prevalence in the group under study is in the moderate (0.20--0.70) range.


Efficacy of a single intravenous administration of laninamivir (an active metabolite of laninamivir octanoate) in an influenza virus infection mouse model.
Laninamivir, a potent neuraminidase (NA) inhibitor, is an active metabolite of laninamivir octanoate (code name: CS-8958) which is a long acting NA inhibitor and is commercially available under the brand name Inavir in Japan to complete the treatment of influenza by a single inhalation. It is supposed that the long acting character is provided by the long retention of laninamivir in the respiratory tract after intranasal administration of laninamivir octanoate in mice and with stable binding of laninamivir to NA of various influenza viruses such as N1, N2 subtypes and NA of B virus. Peramivir, another NA inhibitor, is also approved in Japan as a single intravenous infusion. In spite of the quick disappearance of peramivir from the blood after injection, the reason treatment can be completed by a single administration is thought to be that peramivir showed stable binding to NA with N9 subtype. Therefore, the stable binder, laninamivir is possibly effective by a single intravenous administration in the mouse model infected with influenza viruses. A single intravenous administration of laninamivir and peramivir at 30mg/kg significantly prolonged mice survival at a comparable level in the mouse lethal model infected with the A/PR/8/34 (H1N1) virus. Also, a single intravenous administration of laninamivir and peramivir significantly suppressed virus proliferation in the lungs of mice infected with influenza B virus. Thus, laninamivir may be effective by a single intravenous infusion in treating influenza, the same as peramivir.


Physicians "missing in action": family perspectives on physician and staffing problems in end-of-life care in the nursing home.
To understand the roles of physicians and staff in nursing homes in relation to end-of-life care through narrative interviews with family members close to a decedent. Qualitative follow-up interviews with 54 respondents who had participated in an earlier national survey of 1,578 informants. Brown University interviewers conducted telephone interviews with participants throughout the United States. The 54 participants agreed to a follow-up qualitative interview and were family members or close to the decedent. A five-member, multidisciplinary team to identify overarching themes taped, transcribed, and then coded interviews. Respondents report that healthcare professionals often insufficiently address the needs of dying patients in nursing homes and that "missing in action" physicians and insufficient staffing create extra burdens on dying nursing home residents and their families. Sustained efforts to increase the presence of physicians and improve staffing in nursing homes are suggested to improve end-of-life care for dying residents in nursing homes.


Weakened biological signals: highly-developed eating schemas amongst women are associated with maladaptive patterns of comfort food consumption.
We examine the comfort food preferences and consumption patterns of women with highly versus less developed schemas for cognitive restraint, emotional and situational eating. In an online survey, 196 women provided their personal definition of what constitutes a comfort food, indicated their favourite one, and their level of hunger and fullness as well as emotional state before and after consumption. Low/high (n=32/n=30) schematic groups respectively scored below/above the median on all three factors of the Dutch Eating Behavior Questionnaire (DEBQ). Results support our proposition that complex eating schemas weaken biological signals and produce maladaptive patterns: high schematics preferred high calorie comfort foods, eaten even when feeling full to alleviate negative emotions at the cost of more post-consumption guilt. High schematics reported a lesser post-consumption increase in fullness than low schematics. Low schematics favoured low and high calorie foods equally, their choice motivated by pleasure and positive emotions. High schematics' definitions revealed that comfort foods are eaten to fill a void or when experiencing negative emotions as well as a deep concern with weight gain; low schematics focused on comfort foods' hedonic attributes. Our results highlight the hitherto unexplored influence of possessing all three highly-developed DEBQ eating schemas in reducing the effectiveness of biological signals and leading to maladaptive eating choices and behaviors.


Diaphragmatic lipoma; A benign condition necessitating an aggressive management.
Primary diaphragmatic lipoma (PDL) is a very rare condition. The aim of this paper is to report a case of diaphragmatic lipoma presenting as a case of diaphratmatic hernia with a brief literature review. A 73-year-old female presented with chronic dry cough for three month duration. The patient was stable, there was no significant finding on general, chest and abdominal examination. Chest-x-ray showed vague shadow above the left dome of the diaphragm. Computed tomography scan (CT scan) of the chest revealed a round mass with features consistent with either diaphragmatic hernia or malignancy. The patient underwent resection under general anesthesia and histopathological examination confirmed the diagnosis of PDL. Although PDL is a benign condition, in most of the time, it needs aggressive management because of the possibility of malignancy or other critical diseases.


Support and information needs for patients with non-small cell lung cancer receiving concurrent chemo-radiotherapy treatment with curative intent: Findings from a qualitative study.
Concurrent chemotherapy and radiotherapy treatment (CCRT) is used to treat locally advanced Non-Small Cell Lung Cancer (NSCLC) in patients with suitable fitness. CCRT is associated with significant toxicity and time spent receiving treatment. Our aim was to identify the support and information needs of patients, and where possible their informal caregivers (IC), at key points along the CCRT pathway. Participants were NSCLC patients who were either about to undergo, currently receiving or had finished CCRT. Semi-structured interviews were conducted with participants, and their IC where applicable, at the treatment centre or participants' home. Interviews were audio recorded and transcribed prior to undergoing thematic analysis. Fifteen patients were interviewed; five were interviewed with their IC. Themes of physical, psychological, and practical support needs are identified with associated subthemes exploring specific needs, such as dealing with late treatment effects, and how patients seek support. Information needs prior to, during and following CCRT were also established as predominant themes with subthemes detailing the needs at these time points. Examples include differences in participant desire for toxicity information and life after treatment. The need for disease, treatment and symptom related information and support remains consistent throughout CCRT and beyond. Further information and support for other matters including engaging in regular activities may also be desired. Time allocated within consultations to establish changes in needs or desire for further information may benefit patient and IC experience and QOL.


PKA mediates the effects of monoamine transmitters on the K+ current underlying the slow spike frequency adaptation in hippocampal neurons.
The Ca(2+)-activated K+ current IAHP, which underlies spike frequency adaptation in cortical pyramidal cells, can be modulated by multiple transmitters and probably contributes to state control of the forebrain by ascending monoaminergic fibers. Here, we show that the modulation of this current by norepinephrine, serotonin, and histamine is mediated by protein kinase A in hippocampal CA1 neurons. Two specific protein kinase A inhibitors, Rp-cAMPS and Walsh peptide, suppressed the effects of these transmitters on IAHP and spike frequency adaptation. The effects of the cyclic AMP analog 8CPT-cAMP were also inhibited, whereas muscarinic and metabotropic glutamate receptor agonists had full effect. Intracellular application of protein kinase A catalytic subunit or a phosphatase inhibitor mimicked the effects of monoamines or 8CPT-cAMP. These results demonstrate that monoaminergic modulation of neuronal excitability in the mammalian CNS is mediated by protein phosphorylation.


Prevalence of low back pain in older Brazilians: a systematic review with meta-analysis.
Prevalence of low back pain (LBP) is expected to increase worldwide with aging of the population but its prevalence in older people is not clear, mainly in developing countries. To estimate the prevalence of LBP in older Brazilians. Electronic searches on SciELO, LILACS, MEDLINE, EMBASE and CINAHL, as well as hand-searching identified studies investigating prevalence of LBP in older Brazilians aged 60 years or over. Two independent reviewers selected studies fulfilling the inclusion criteria, assessed risk of bias for each included study and extracted relevant data. Meta-analysis was conducted when enough homogeneity allowed and the GRADE system was used to summarize the overall quality of the evidence. Sixteen studies were included with a total of 28,448 participants. Data from point- and period-prevalence of LBP were obtained. Meta-analysis was conducted for 13 studies reporting point-prevalence. Pooled point-prevalence of LBP was 25.0% (95% CI 18.0-32.0). Other three studies investigated period-prevalence: one-week prevalence=15.0% (95% CI 13.0-18.0); six-month prevalence=43.0% (95% CI 42.0-44.0); and 12-month prevalence=13.0% (95% CI 11.0-16.0). Sensitivity analyses were performed for point-prevalence and exclusion of studies with poorer methodological quality tended to increase the estimated prevalence of LBP. Moderate-quality evidence showed that at any point in time one in four older Brazilians suffers from LBP. This was the first systematic review investigating nationwide data on the prevalence of LBP in older people and contributes important clinical and epidemiological evidence for policymakers.


Evaluating the efficacy of endodontic microsurgery for teeth with an undeveloped root apex and periapical periodontitis after nonsurgical treatment failure.
To determine the efficacy of endodontic microsurgery for teeth with an undeveloped root apex and periapical periodontitis caused by an abnormal central cusp fracture after failed nonsurgical treatment. Eighty teeth in 78 patients were subjected to endodontic microsurgery. All patients were clinically and radiologically examined 1 year postoperatively. The data were statistically analyzed using SPSS 27.0 software. Of the 80 teeth in 78 patients, periapical lesions had disappeared in 77 teeth at 1-year postoperative follow-up, with a success rate of approximately 96.3% (77/80). The efficacy of endodontic microsurgery was not affected by sex, age, extent of periapical lesions, and presence of the sinus tract. Between-group differences were not statistically significant (P > 0.05). Endodontic microsurgery can be an effective alternative treatment option for teeth with an undeveloped root apex and periapical periodontitis caused by an abnormal central cusp fracture after nonsurgical treatment failure.


The detection of oral pre- malignant lesions with an autofluorescence based imaging system (VELscope™) - a single blinded clinical evaluation.
The disease specific five-year survival rate especially for patients with advanced oral cancer has not improved significantly over the period of time. The most effective way of combating this dilemma is an early detection, diagnosis and eradication of early-stage lesions and their precursors. The use of VELscope® using an autofluorescence as a diagnostic tool might be useful in early detection of oral malignant lesions. 120 patients with suspicious oral premalignant lesions were examined with two examination methods. They were randomly divided into two groups. Group 1 was examined conventional with white-light and group 2 was examined additionally to the white-light-examination with an autofluorescence visualization device, VELscope®. Biopsies were obtained from all suspicious areas identified in both examination groups (n = 52). The diagnostic strategies were compared regarding sensitivity and specificity. Based upon the result, use of the VELscope® leads to a higher sensitivity (22.0%), but regarding specificity the additional use of the VELscope® is inferior (8.4%). The VELscope device is a simple, non-invasive test of the oral mucosa, which can help the experienced clinician to find oral precursor malignant lesions.


Size of bony labyrinth of human infant and adult compared to that in certain animals.
Comparative anatomic studies of the bony labyrinths of humans and those of a full grown pony, zebra, grizzly bear, seal and domestic cow were performed. Fusible metal was injected into the labyrinths and the resultant casts were then measured. The similarities and differences were noted and discussed.


Factors influencing outcomes of nonsurgical treatment for baseball players with SLAP lesion.
Superior labrum anterior posterior (SLAP) lesion of the shoulder joint occurs in throwing athletes as a results of overuse, such as from repetitive baseball pitching. Nonsurgical treatments are usually the first-line therapy for symptomatic SLAP lesion. However, some patients cannot obtain satisfactory improvement of their symptoms, leading to dysfunction of the shoulder and diminished pitching performance. The purpose of this study was to analyze factors that influence outcomes of nonsurgical treatments for SLAP lesion. Forty-five baseball players with SLAP lesion, whose mean age was 21.6 (range, 16-36) years and who underwent nonsurgical treatments, were the subjects of this study. SLAP lesion was diagnosed by shoulder arthrography and magnetic resonance imaging (MRI). Exclusion criteria included definite associated trauma such as dislocation, fracture or injuries related to sports activities. Playing positions included pitcher (21 patients), catcher (3 patients), infielder (13 patients) and outfielder (8 patients). Mean symptomatic duration from the onset of shoulder pain to the beginning of nonsurgical treatments was 8.5 (range, 1-72) months. Nonsurgical treatments included physical therapy, such as range of motion, stretching, and rotator cuff exercises, as well as prescription of nonsteroidal anti-inflammatory drugs if necessary. To identify factors that influenced outcomes of nonsurgical treatments for SLAP lesion, various factors of 13 nonresponsive patients were compared with those of 32 patients who responded to nonsurgical treatment. The factors were as follows: patient background, such as age or playing position; range of shoulder motion; shoulder joint laxity; and findings of radiographs and MRI. All data were statistically assessed using logistic analysis and Spearman's correlation coefficient. The significance level was set at P < 0.05, and odds ratios were determined. Factors identified as having significant difference between the 2 groups were age, duration of baseball experience, symptomatic period, playing position, range of internal and external rotation in the first medical examination, range of total rotation of 90° abduction 2 months after nonsurgical treatments, and presence of Bennett spur and partial-thickness tears of the articular-side rotator cuff. Factors with high odds ratios were symptomatic period, range of total rotation of 90° abduction 2 months after the treatment, age, and duration of baseball experience. Symptomatic period, duration of baseball experience, age, and findings of radiographs and MRI are inevitable factors that cannot be improved by nonsurgical treatment. On the other hand, restriction of shoulder motion due to posterior muscular tightness is a factor that can be improved by nonsurgical treatment. Early improvement of shoulder motion is important to obtain satisfactory outcomes of nonsurgical treatments for SLAP lesion.


Combined molecular, structural and memory data unravel the destructive effect of tramadol on hippocampus.
Tramadol is a synthetic analogue of codeine and stimulates neurodegeneration in several parts of the brain that leads to various behavioral impairments. Despite the leading role of hippocampus in learning and memory as well as decreased function of them under influence of tramadol, there are few studies analyzing the effect of tramadol administration on gene expression profiling and structural consequences in hippocampus region. Thus, we sought to determine the effect of tramadol on both PC12 cell line and hippocampal tissue, from gene expression changes to structural alterations. In this respect, we investigated genome-wide mRNA expression using high throughput RNA-seq technology and confirmatory quantitative real-time PCR, accompanied by stereological analysis of hippocampus and behavioral assessment following tramadol exposure. At the cellular level, PC12 cells were exposed to 600 μM tramadol for 48 hrs, followed by the assessments of ROS amount and gene expression levels of neurotoxicity associated with neurodegenerative pathways such as apoptosis and autophagy. Moreover, the structural and functional alteration of the hippocampus under chronic exposure to tramadol was also evaluated. In this regard, rats were treated with tramadol at doses of 50 mg/kg for three consecutive weeks. In vitro data revealed that tramadol provoked ROS production and caused the increase in the expression of autophagic and apoptotic genes in PC12 cells. Furthermore, in-vivo results demonstrated that tramadol not only did induce hippocampal atrophy, but it also triggered microgliosis and microglial activation, causing upregulation of apoptotic and inflammatory markers as well as over-activation of neurodegeneration. Tramadol also interrupted spatial learning and memory function along with long-term potentiation (LTP). Taken all together, our data disclosed the neurotoxic effects of tramadol on both in vitro and in-vivo. Moreover, we proposed a potential correlation between disrupted biochemical cascades and memory deficit under tramadol administration.


Purification and biochemical characterization of a lysosomal α-fucosidase from the deuterostomia Asterias rubens.
In vertebrates, mannose 6-phosphate receptors [MPR300 (Mr 300 kDa) and MPR46 (Mr 46 kDa)] are highly conserved transmembrane glycoproteins that mediate transport of lysosomal enzymes to lysosomes. Our studies have revealed the appearance of these putative receptors in invertebrates such as the molluscs and deuterostomes. Starfish tissue extracts contain several lysosomal enzyme activities and here we describe the affinity purification of α-fucosidase. The purified enzyme is a glycoprotein that exhibited a molecular mass of ∼56 kDa in SDS-PAGE under reducing conditions. It has also cross-reacted with an antiserum to the mollusc enzyme suggesting antigenic similarities among the two invertebrate enzymes. LC-MS/MS analysis of the proteolytic peptides of the purified enzyme in combination with de novo sequencing allowed us to do partial amino acid sequence determination of the enzyme. These data suggest that this invertebrate enzyme is homologous to the known mammalian enzyme. The purified enzyme exhibited a mannose 6-phosphate dependent interaction with the immobilized starfish MPR300 protein. Our results demonstrate that the lysosomal enzyme targeting pathway is conserved even among the invertebrates.


Starch propionylation acts as novel encapsulant for probiotic bacteria: A structural and functional analysis.
Propionylated potato starch (PPS) with different degrees of substitution (DS) was prepared from native potato starch (NPS) and their potential to encapsulate Lactobacillus rhamnosus GG (LGG) was analyzed. Fourier transform infrared spectroscopy (FTIR) showed a characteristic peak of propionyl groups, which appeared at 1746 cm-1, demonstrating that propionylation occurred. X-ray diffraction (XRD) results revealed that the characteristic diffraction peak intensity of PPS gradually disappeared with the increasing of the DS, which was related to the loss of the ordered crystalline structure of starch granules. Propionylation resulted in the starch to be more thermally stable than its native starch. Furthermore, the propionylated starch had a higher resistance to digestion and hydrophobicity. More importantly, the micro-capsulated LGG derived from propionylated starch could achieve a maximum embedding efficiency of 87.77% at starch DS = 1.54, and also demonstrated a higher resistance to a strong acidic condition and a greater storage stability at 4 °C. This study may highlight a novel approach for probiotic encapsulation using propionylated potato starch as an encapsulant.


Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus.
Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in Zn2+-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn2+-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn2+ entry in the inward-facing conformation and widens the luminal cavity for Zn2+ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn2+ ions, seemingly facilitating Zn2+ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn2+ uptake into the Golgi to be proposed.


Nomogram for individually predicting overall survival in rectal neuroendocrine tumours.
This study aimed to develop a nomogram that predicts the overall survival (OS) of rectal neuroendocrine tumours (NETs). We retrospectively analysed 310 patients with rectal neuroendocrine tumours in 5 hospitals in southern China. All of the patients were assigned to the training set. A multivariable analysis using Cox proportional hazards regression was performed using the training set, and a nomogram was constructed. It was validated on a dataset obtained from the Surveillance, Epidemiology, and End Result (SEER) database of America (n = 547). In the training set, the nomogram exhibited improved discrimination power compared with the WHO grade guidelines (Herrell's C-index, 0.872 vs 0.794; p < 0.001) and was also better than the seventh AJCC TNM classification (Herrell's C-index, 0.872 vs 0.817; p < 0.001). In the SEER validation dataset, the discrimination was also excellent (C-index, 0.648 vs 0.583, p < 0.001 and 0.648 vs 0.603, p = 0.016, respectively, compared with G grade and TNM classification). Calibration of the nomogram predicted individual survival corresponding closely with the actual survival. We developed a nomogram predicting 1- and 3-year OS of patients with rectal neuroendocrine tumours. Validation revealed excellent discrimination and calibration, suggesting good clinical utility.


Iatrogenic orbital cerebrospinal fluid leak in a young pediatric patient: Factors to consider.
Orbital abscess and subperiosteal abscess are pathologies which may require surgical treatment in the pediatric patient. Though rare, orbital cerebrospinal fluid (CSF) leak is a serious complication of abscess drainage. This paper presents a unique 5-month-old male with transorbital abscess drainage complicated by CSF leak. An endoscope was used to repair the defect through the orbitotomy incision. There was no evidence of persistent leak at follow-up. The surgical approach likely contributed to the complication, and the otolaryngologist played a key role in the leak repair. This case should serve to raise the awareness regarding considerations to avoid orbital CSF leak.


The introduction of colonic-Bacteroides shuttle plasmids into Porphyromonas gingivalis: identification of a putative P. gingivalis insertion-sequence element.
Two Escherichia coli-Bacteroides plasmid-shuttle vectors pNJR5 and pNJR12 were introduced for the first time into Porphyromonas gingivalis W83 by conjugal transfer from E. coli. The transfer frequencies were comparable to those obtained when using colonic Bacteroides as recipients. Both plasmids were maintained in P. gingivalis W83 and could be isolated and introduced back into E. coli. Plasmid DNA extracted from one P. gingivalis W83 pNJR12 transconjugant had an additional 1.5 kb of inserted DNA. Southern-blot analysis of P. gingivalis W83 chromosomal DNA using this inserted DNA as a probe revealed the presence of multiple copies of this sequence on the chromosome. We propose that this DNA represents a P. gingivalis insertion sequence (IS) element and should be referred to as IS1126. This is the first IS element to be isolated from a Gram-negative oral anaerobic bacterium.


Influence of gaseous VOC concentration on the diversity and biodegradation performance of microbial communities.
In this work, the influence of toluene gas concentration on the isolation of toluene degrading microbial communities from activated sludge was studied. Toluene biodegradation at gas phase concentration of 10 g m(-3) (R1) resulted in process instability with removal efficiencies (RE) lesser than 33 %, while operation at toluene gas phase concentrations of 300 mg m(-3) (R2) and 11 mg m(-3) (R3) was stable with RE ranging from 74 to 94 %. The consortium isolated in R1 exhibited the highest tolerance toward toluene but the lowest biodegradation performance at trace level VOC concentrations. Despite R2 and R3 showed a similar sensitivity toward toluene toxicity, the microbial community from R2 supported the most efficient toluene biodegradation at trace level VOC concentrations. The Shannon-Wiener index showed an initial biodiversity decrease from 3.2 to 2.0, 1.9 and 2.7 in R1, R2 and R3, respectively. However, while R2 and R3 were able to recover their initial diversity levels by day 48, this loss in diversity was permanent in R1. These results showed that traditional inoculum isolation/acclimation techniques based on the exposure of the inoculum to high VOC concentrations, where toxicity tolerance plays a key role, may result in a poor abatement performance when the off-gas stream is diluted.


Proteomics study reveals the molecular mechanisms underlying cryotolerance induced by mild sublethal stress in human sperm.
The preconditioning of human sperm with sublethal nitrosative stress before cryopreservation can potentially improve the thawed sperm quality. However, the underlying mechanisms behind this protective strategy are not entirely understood. We compared the cryosurvival of human sperm exposed to 0.01 μM nitric oxide (NO) throughout the cryopreservation and used multiplexed quantitative proteomics approach to identify changes in the proteome profile of preconditioned sperm cells. Semen samples were obtained from 30 normospermia donors and then each sample was divided into three equal parts: fresh (F), frozen-control (C), and frozen exposed to nitric oxide (NO). The sperm undergoing mild sublethal stress showed higher values for motility and viability compared to the frozen control sperm. Moreover, out of 2912 identified proteins, 248 proteins were detected as differentially abundant proteins (DAPs) between cryopreserved groups and fresh group (F) (p < 0.05). Gene ontology (GO) analysis of differentially abundant proteins indicated that the abundance of proteins associated with glycolysis, gluconeogenesis, and fertilization processes was reduced while oxidative phosphorylation pathway was increased in abundance in cryopreserved sperm compared to the fresh sperm. Moreover, redox protein such as thioredoxin 17 was increased in abundance in the NO group compared to the control freezing group. Therefore, the pre-conditioning of sperm prior to cryopreservation may play an important role in maintaining the redox balance in mitochondria of sperm after freezing. Overall, our results indicate that arylsulfatase A (ARSA), serine protease 37 (PRSS37), and sperm surface protein (SP17) may potentially serve as protein biomarkers associated with screening the fertilization potential of the thawed sperm.


131I thyroid activity and committed dose assessment among family members of patients treated with radioactive iodine.
The main goal of the present study was estimation of an internal contamination of 131I among family members of patients treated with radioactive iodine. Thyroid activity measurements of 131I in examined volunteers were performed using a whole-body spectrometer at the institute of nuclear physics, Polish academy of sciences. During this research, 20 relatives of patients treated with 131I were examined: eight women and 12 men with an age in the range from 3 to 72 years. In the case of nine individuals, the activity of 131I in the thyroid was below the detection limit, but among the remaining 11 individuals, the activity varied from (9 ± 3) Bq up to (1140 ± 295) Bq. Subsequently, based on the measurements of thyroid 131I activities, the corresponding doses were assessed. The highest estimated effective dose reached 218 μSv, while the thyroid equivalent dose was 2.4 mSv. In addition, the experimental data obtained were statistically analysed together with the results of surveys of the individuals participating in the study by means of correspondence analysis and nonparametric tests: Mann-Whitney, gamma, χ2 and Yule Phi coefficient. These analyses revealed relationships between 131I activities in the thyroids of the examined individuals and their housing conditions as well as consumption of meals prepared by the patients.


Life cycle and techno-economic assessment of source-separated wastewater-integrated microalgae biofuel production plant: A nutrient organization approach.
Microalgae cultivating in wastewater enabling nutrient uptake for biomass and biofuel generation is regarded as a promising pathway to increase sustainability of microalgae biofuel production process. A source-separated nutrient organization approach for the process of wastewater-based microalgae biofuel is proposed in this study. Comparative life cycle assessment (LCA) method and Techno-economic analysis (TEA) approach are employed to assess sustainability and economic performance of the proposed nutrient approach. Two scenarios are used to validate our study. Scenario 1 is based on the source-separated nutrient delivery approach with microalgae integrated wastewater in tertiary treatment. Scenario 2 is based on non-separated-point nutrient delivery policy and microalgae integrated with secondary wastewater treatment. The results show that the source-separated nutrient approach is effective for reducing the environmental impacts and increasing commercial potential of microalgae biofuel.


Factors associated with postpartum women's knowledge, attitude and practice regarding human milk banks and milk donation: A cross-sectional survey.
Breast milk is the optimal method of human nutrition, and donor human milk is often needed to reduce the incidence of necrotizing enterocolitis and septicemia in preterm infants and improve their survival rate. Donor human milk is recommended as the first alternative when mothers' milk is not available. The establishment of human milk banks is of great significance to promote the breastfeeding of preterm infants. However, there are insufficient studies on human milk banks and milk donation in China. (1) To investigate postpartum women's knowledge, attitude and practice regarding human milk banks and milk donation and to analyze the influencing factors. (2) To explore reasons why postpartum women reject milk donation and donor milk. A cross-sectional survey was conducted from February 2019 to July 2019 at two hospitals in Wuhan, a large city in central China. Mothers who returned to hospital for postpartum follow-up within six months participated in this survey (N = 1078). Questionnaires were used to obtain sociodemographic data and to determine participants' knowledge, attitude and practice regarding human milk banks and milk donation. Of the respondents, 216 (20%) had prior knowledge of human milk banks and milk donation. For the sub-domain of knowledge, the item with the highest correct response rate was the benefit of breast milk, and the item with the lowest correct rate was the acceptance of donor human milk. For the sub-domain of attitude, 811(75.3%) of participants held a supportive attitude for the establishment of human milk banks, and 877(81.3%) were supportive of donating breast milk while 412 (38.3%) were supportive of accepting donor human milk. For the sub-domain of practice, the practice of milk donation was not optimistic as participants lacked interest in donating breast milk and spreading knowledge of breast milk banks, and only 28.3% of participants indicated that they would donate breast milk continuously. Participants' age, educational background, weight of the newborn and having prior knowledge of human milk banks were factors that could positively predict their knowledge, attitude and practice associated with human milk banks and milk donation; medication usage during pregnancy or lactation was a factor negatively predicting their knowledge about human milk banks and milk donation. This study reveals that a majority of postpartum women are supportive of human milk banks and more willing to donate breast milk than receive donor milk. Lack of knowledge about human milk banks and safety concerns are the main factors hindering postpartum women from donating or accepting donor milk. Findings suggest that it is important to enhance public awareness regarding human milk banks as potential resources for life-saving therapy for preterm infants.This information should be disseminated during the early stage of the establishment of human milk banks. Moreover, health education of pregnant women should include the importance of human milk as well as the alternative and safety of donor milk from milk banks, especially for promoting the health of preterm infants and infants who are unable to receive mothers' breastmilk.


AIP1 and cofilin ensure a resistance to tissue tension and promote directional cell rearrangement.
In order to understand how tissue mechanics shapes animal body, it is critical to clarify how cells respond to and resist tissue stress when undergoing morphogenetic processes, such as cell rearrangement. Here, we address the question in the Drosophila wing epithelium, where anisotropic tissue tension orients cell rearrangements. We found that anisotropic tissue tension localizes actin interacting protein 1 (AIP1), a cofactor of cofilin, on the remodeling junction via cooperative binding of cofilin to F-actin. AIP1 and cofilin promote actin turnover and locally regulate the Canoe-mediated linkage between actomyosin and the junction. This mechanism is essential for cells to resist the mechanical load imposed on the remodeling junction perpendicular to the direction of tissue stretching. Thus, the present study delineates how AIP1 and cofilin achieve an optimal balance between resistance to tissue tension and morphogenesis.


Application effect of sterile normal saline ice for post-partum hemorrhage at the time of cesarean delivery: A retrospective review.
Post-partum hemorrhage (PPH) is a common complication of cesarean sections (CS) and affects maternal and newborn health. We used a new method to control bleeding and compared its efficacy with conventional methods. Eighty-six women who experienced PPH with volume of bleeding over 1000 mL in CS between January 2008 and January 2012 were chosen as samples. Thirty-three underwent the new method in which normal saline ice blocks are placed in the uterus, and 53 underwent the conventional method. We evaluated blood loss, volume of transfusion and complications. Patients who were treated with ice blocks had better hemostatic efficacy than those who underwent the conventional method (1450 ± 251.9 mL vs 1800 ± 278.9 mL; P < 0.001); they also had less blood transfusion (806.1 ± 242.3 mL vs 1222.6 ± 308.0 mL; P < 0.001), lower rate of hysterectomy and infection (3.03% vs 5.66%; P = 0.971; 0% vs 7.55%; P = 0.276), and shorter duration of hospital stay (5.3 ± 0.5 days vs 7.6 ± 3.0 days; P < 0.001). PPH in CS can be treated with peeled sterile normal saline ice blocks, a simple and reliable method for stopping bleeding. Nonetheless, there needs to be a large randomized control trial for confirmation.


Patterns of health-promoting behaviors and associated factors in family caregivers of people receiving cancer treatment: A latent class profile analysis.
Family caregivers tend to neglect their health while prioritizing the needs of their care recipients. Identifying subgroups of caregivers based on the patterns of health-promoting behaviors (HPBs) may help develop tailored interventions for them, yet little is known. The purpose of this study was: (1) to identify latent classes with distinct patterns of HPBs in family caregivers of people with cancer; and (2) to investigate factors associated with the latent class membership. We performed a cross-sectional data analysis using the baseline dataset from a longitudinal survey study that assessed HPBs of family caregivers of individuals who received cancer treatment at a national research hospital (N = 124). Latent class profile analysis was conducted to identify latent classes based on the subdomains of the Health-Promoting Lifestyle Profile II, followed by multinomial logistic regression analysis to investigate factors associated with the latent class membership. Three latent classes were identified: a high level of HPB (Class 1, 25.8%); a moderate level of HPB (Class 2, 53.2%); and a low level of HPB (Class 3, 21.0%) of HPBs. Controlling for caregiver age and sex, caregiver burden due to lack of family support, perceived stress, self-efficacy and body mass index were factors associated with the latent class membership. HPBs of our caregiver sample appeared in relatively stable patterns at different levels. Higher caregiver burden and perceived stress and lower self-efficacy were associated with the lower practice of HPBs overall. Our findings may serve as a reference for screening caregivers who need support and developing person-centered interventions.


TKA patients with unsatisfying knee function show changes in neuromotor synergy pattern but not joint biomechanics.
Nearly 20% of patients who have undergone total knee arthroplasty (TKA) report persistent poor knee function. This study explores the idea that, despite similar knee joint biomechanics, the neuro-motor synergies may be different between high-functional and low-functional TKA patients. We hypothesized that (1) high-functional TKA recruit a more complex neuro-motor synergy pattern compared to low-functional TKA and (2) high-functional TKA patients demonstrate more stride-to-stride variability (flexibility) in their synergies. Gait and electromyography (EMG) data were collected during level walking for three groups of participants: (i) high-functional TKA patients (n=13); (ii) low-functional TKA patients (n=13) and (iii) non-operative controls (n=18). Synergies were extracted from EMG data using non-negative matrix factorization. Analysis of variance and Spearman correlation analyses were used to investigate between-group differences in gait and neuro-motor synergies. Results showed that synergy patterns were different among the three groups. Control subjects used 5-6 independent neural commands to execute a gait cycle. High functional TKA patients used 4-5 independent neural commands while low-functional TKA patients relied on only 2-3 independent neural commands to execute a gait cycle. Furthermore, stride-to-stride variability of muscles' response to the neural commands was reduced up to 15% in low-functional TKAs compared to the other two groups.


The role of the lymphatic system in acute arterial prosthetic graft infections.
No experimental data have been published that evaluate the role of lower extremity lymphatics in the pathophysiology of arterial graft infection. Bilateral interpositional femoral artery graft (PTFE) replacements were performed in 21 greyhounds, accompanied by unilateral limb ischemia-rendering operations and ipsilateral bacterial inoculations with standardized inocula of Escherichia coli and Staphylococcus aureus. Inguinal lymphatics in the ischemic leg were either simply transected (group I), carefully preserved (group II), or excised and ligated (group III) at the time of femoral graft implantation. The grafts were harvested 48 hours later and graft and blood cultures obtained. There was an 87.5% incidence of positive graft cultures in groups I and II, but both organisms were cultured significantly more often in group II than in group I (62.5% vs. 12.5%; p less than 0.01). Blood culture data were similar. The incidence of positive graft and blood cultures in group III was only 20%, and no cultures obtained were positive for both organisms. Cultures of contralateral control grafts yielded both organisms in all group II dogs compared with only 25% of group I and 0% in group III (p less than 0.01). These results suggest that the lymphatics probably contribute to the development of acute graft infection by absorbing bacteria, and either transporting them to the systemic circulation via lymphatic-venous communications when the lymphatics are intact, causing hematogenous contamination of a graft, or by directly bathing the implanted graft when the lymphatics are disrupted proximal to a septic focus. Careful isolation, transection, and ligation of the inguinal lymphatics at the time of arterial reconstruction might minimize acute graft sepsis.


Low temperature deposition of 2D WS2 layers from WF6 and H2S precursors: impact of reducing agents.
We demonstrate the impact of reducing agents for Chemical Vapor Deposition (CVD) and Atomic Layer Deposition (ALD) of WS2 from WF6 and H2S precursors. Nanocrystalline WS2 layers with a two-dimensional structure can be obtained at low deposition temperatures (300-450 °C) without using a template or anneal.


Development of accessory phenotype and function during the differentiation of monocyte-derived dendritic cells.
Dendritic cells (DCs) are professional antigen-presenting cells (APCs), and classical DCs, such as Langerhans cells (LCs) or interdigitating DCs (IDCs) are known to be the most potent stimulators of T lymphocytes. Earlier, several groups described the generation of DCs from monocytes, starting with peripheral blood mononuclear cells (PBMCs), adherent cells or magnetic bead-purified CD14+ cells. Although modifications of the original protocols have already been described, some questions relevant to clinical application and basic studies have not yet been addressed. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL4) appear to be necessary, but are not sufficient for the differentiation of monocyte-derived dendritic cells (MoDCs), as indicated by the failure to generate such cells under serum-free conditions. Using adherence purified monocytes, we first investigated the amount of GM-CSF and IL4 required for the differentiation of DCs. Consecutive kinetic studies during the differentiation period were designed to demonstrate how monocytes acquire the phenotype and function of DCs. The results showed that small amounts of GM-CSF and IL4 were required to generate MoDC which acquired their phenotype and function within 4 days. IL13 may substitute for IL4, whereas IL10, TNF alpha or IFN gamma inhibited the generation of MoDCs.


A systemized approach for evaluation and adjustment of complete dentures.
Because of the vast numbers of potential symptoms and causes, a systematic method is needed to assess patient complaints about fit, esthetics, and feel of complete dentures, permitting the dentist to establish planned corrective procedures. One system is the SOAP method of problem-oriented record notations that defines a systematic way of dealing clinically with patient problems.


An aging-related signature predicts favorable outcome and immunogenicity in lung adenocarcinoma.
Aging has been demonstrated to play vital roles in the prognosis and treatment efficacy of cancers, including lung adenocarcinoma (LUAD). This novel study aimed to construct an aging-related risk signature to evaluate the prognosis and immunogenicity of LUAD. Transcriptomic profiles and clinical information were collected from a total of 2518 LUAD patients from 12 independent cohorts. The risk signature was developed by combining specific gene expression with the corresponding regression coefficients. One cohort treated with the immune checkpoint inhibitor (ICI) was also used. Subsequently, a risk signature was developed based on 21 aging-related genes. LUAD patients with low-risk scores exhibited improved survival outcomes in both the discovery and validation cohorts. Further immunology analysis revealed elevated lymphocyte infiltration, decreased infiltration of immune-suppressive cells, immune response-related pathways, and favorable ICI predictor enrichment in the low-risk subgroup. Genomic mutation exploration indicated the enhanced mutation burden and higher mutation rates in significantly driver genes of TP53, KEAP1, SMARCA4, and RBM10 were enriched in patients with a low-risk signature. In the immunotherapeutic cohort, it was observed that low-risk aging scores were markedly associated with prolonged ICI prognosis. Overall, the estimated aging signature proved capable of evaluating the prognosis, tumor microenvironment, and immunogenicity, which further provided clues for tailoring prognosis prediction and immunotherapy strategies, apart from promoting individualized treatment plans for LUAD patients.


The grandmultipara: is she still a risk?
Grandmultiparity is reported to increase both maternal and perinatal mortality and morbidity. Unique religious and demographic factors in Jerusalem allowed us to analyze a population wherein parity could be dissociated from socioeconomic status. A total of 7785 mothers was studied, 889 (11.5%) of whom were grandmultiparas. Comparison of grandmultiparous mothers with all others revealed no increase in the incidence of hypertension, diabetes, uterine atonia, antenatal or postnatal hemorrhage, cesarean sections, stillbirth rate, or congenital malformations. The grandmultipara had significantly lower neonatal mortality and low birth weight rates and a significantly higher incidence of multiple births and trisomy 21 (p less than 0.01). These results strongly suggest that grandmultiparity in and of itself in a healthy, economically stable population afforded modern medical care is not a major risk factor and that previous reports primarily reflected social class factors and not parity per se.


Fatal proliferative glomerulonephritis in lepromatous leprosy.
A patient of lepromatous leprosy with recurrent erythema nodosum leprosum developing acute renal failure proving fatal within 8 weeks is reported. The renal lesion demonstrated acute proliferative glomerulonephritis. Its pathogenesis in relation to ENL is discussed.


The effect of pituitary-adrenal function in the modulation of pain sensitivity in the rat.
1. The relationship between adrenalcortical hormones, adrenocorticotrophic hormone (ACTH), and pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 degrees C.2. Bilateral adrenalectomy increased the sensitivity to pain, but adrenal demedullation had no effect.3. Pain sensitivity was inversely related to the circadian changes in circulating corticosterone and was greater at 7 a.m. than at 7 p.m. However, the same variation in pain sensitivity existed if the adrenals were removed, suggesting that the increase in pain sensitivity after adrenalectomy was not related directly to the levels of corticosteriods.4. The time course of the increase in pain sensitivity after adrenalectomy paralleled that of the changes in circulating ACTH. Adrenalectomy markedly increased pain sensitivity at 9 and 18 days following surgery when circulating ACTH levels were markedly elevated and corticosterone was absent, but not at 3 days following adrenalectomy when ACTH levels were lower and corticosterone was absent.5. Hypophysectomy decreased the sensitivity to pain.6. The results indicate that ACTH can alter pain sensitivity and that the effect of corticosteroids on the sensitivity to pain is an indirect one by virtue of their negative feed-back action on the hypothalamic-pituitary system.


Transcriptome analysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest.
Plants produce a vast array of specialized metabolites, many of which are used as pharmaceuticals, flavors, fragrances, and other high-value fine chemicals. However, most of these compounds occur in non-model plants for which genomic sequence information is not yet available. The production of a large amount of nucleotide sequence data using next-generation technologies is now relatively fast and cost-effective, especially when using the latest Roche-454 and Illumina sequencers with enhanced base-calling accuracy. To investigate specialized metabolite biosynthesis in non-model plants we have established a data-mining framework, employing next-generation sequencing and computational algorithms, to construct and analyze the transcriptomes of 75 non-model plants that produce compounds of interest for biotechnological applications. After sequence assembly an extensive annotation approach was applied to assign functional information to over 800,000 putative transcripts. The annotation is based on direct searches against public databases, including RefSeq and InterPro. Gene Ontology (GO), Enzyme Commission (EC) annotations and associated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway maps are also collected. As a proof-of-concept, the selection of biosynthetic gene candidates associated with six specialized metabolic pathways is described. A web-based BLAST server has been established to allow public access to assembled transcriptome databases for all 75 plant species of the PhytoMetaSyn Project (www.phytometasyn.ca).