Histological chorioamnionitis and the risk of early intraventricular hemorrhage in infants born < or =28 weeks gestation.
To test the hypothesis that histological chorioamnionitis (CA) is not associated with increased risk of early onset intraventricular hemorrhage (IVH). Clinical data were prospectively collected for 62 consecutive neonates born before 28 weeks of gestation. Placental histology for CA was performed by a pathologist unaware of the head ultrasound scan (HUS) results. The first HUS was obtained by 30 minutes of life. Follow-up HUS were performed before 24 hours and again at 48 to 72 postnatal hours of life. An IVH (grade I to IV) at less than 72 hours of life was deemed an early hemorrhage. Nine of the 62 (14.5%) infants had early onset IVH. In all, 29 infants were born to women with histological evidence of CA; 33 infants did not have CA. Infants did not differ in birth weight, gestational age, sex, cord blood pH, 5-minute Apgar score of <7, cesarean delivery, prenatal use of steroids, administration of tocolytics, need for resuscitation, presence of pneumothorax, platelet count at birth, or use of surfactant. Early IVH rates (3/29 in CA vs 6/33 in non-CA) were similar (p=0.48). Two infants in each group with early IVH died before 2 weeks of age. Five additional infants from the CA group developed IVH at more than 72 postnatal hours of life (late onset IVH), and two of those infants progressed to develop periventricular leukomalacia (PVL). In contrast, only three non-CA infants had late IVH and none developed PVL. Logistic regression confirmed that no perinatal variables including CA were associated with early onset IVH. Chorioamnionitis is not associated with increased risk of early IVH.


Ramadan Fasting Decreases Body Fat but Not Protein Mass.
Many studies have shown various results regarding the effects of Ramadan fasting on weight and body composition in healthy individuals. This study aimed to evaluate the effect of Ramadan fasting on body composition in healthy Indonesian medical staff. In this study, we examined the influence of Ramadan fasting on body composition in healthy medical staff. The longitudinal study was performed during and after Ramadan fasting in 2013 (August to October). Fourty-three medical staff members (physicians, nurses and nutritionists) at the Internal Medicine Ward of the Dr. Cipto Mangunkusumo General Hospital were measured to compare their calorie intake, weight, body mass index, waist-to-hip ratio (WHR), and body composition, including body fat, protein, minerals and water, on the first and 28(th) days of Ramadan and also 4-5 weeks after Ramadan fasting. Measurements were obtained for all 43 subjects on the 28(th) day of Ramadan, but they were obtained for only 25 subjects 4 - 5 weeks after Ramadan. By the 28(th) day of Ramadan, it was found that the body weight, BMI, body fat, water and mineral measures had decreased significantly (-0.874 ± 0.859 kg, P < 0.001; -0.36 ± 0.371 kg/m(2), P < 0.001; -0.484 ± 0.597 kg, P < 0.001; -0.293 ± 0.486 kg, P = 0.001; -0.054 ± 0.059 kg, P < 0.001, respectively). Protein body mass and calorie intake did not significantly change (-0.049 ± 0.170 kg, P = 0.561; 12.94 ± 760.608 Kcal, P = 0.082 respectively). By 4 - 5 weeks after Ramadan, body weight and composition had returned to the same levels as on the first day of Ramadan. Ramadan fasting resulted in weight loss even it was only a temporary effect, as the weight was quickly regained within one month after fasting. The catabolism catabolic state, which is related to protein loss, was not triggered during Ramadan fasting. Further research is needed to evaluate the effects of weight loss during Ramadan fasting in healthy individuals.


Biochemical Characterization of a Novel Monospecific Endo-β-1,4-Glucanase Belonging to GH Family 5 From a Rhizosphere Metagenomic Library.
Cellulases have a broad range of different industrial applications, ranging from food and beverages to pulp and paper and the biofuels area. Here a metagenomics based strategy was used to identify the cellulolytic enzyme CelRH5 from the rhizosphere. CelRH5 is a novel monospecific endo-β-1,4-glucanase belonging to the glycosyl hydrolase family 5 (GH5). Structural based modeling analysis indicated that CelRH5 is related to endo-β-1,4-glucanases derived from thermophilic microorganisms such as Thermotoga maritima, Fervidobacterium nodosum, and Ruminiclostridium thermocellum sharing 30-40% amino acid sequence identity. The molecular weight of the enzyme was determined as 40.5 kDa. Biochemical analyses revealed that the enzyme displayed good activity with soluble forms of cellulose as a substrate such as ostazin brilliant red hydroxyethyl cellulose (OBR-HEC), carboxymethylcellulose (CMC), hydroxyethyl cellulose (HEC), and insoluble azurine cross-linked hydroxyethylcellulose (AZCL-HEC). The enzyme shows highest enzymatic activity at pH 6.5 with high pH tolerance, remaining stable in the pH range 4.5-8.5. Highest activity was observed at 40°C, but CelRH5 is psychrotolerant being active and stable at temperatures below 30°C. The presence of the final products of cellulose hydrolysis (glucose and cellobiose) or metal ions such as Na+, K+, Li+, and Mg2+, as well as ethylenediaminetetraacetic acid (EDTA), urea, dithiothreitol (DTT), dimethyl sulfoxide (DMSO), 2-mercaptoethanol (2-ME) or glycerol, did not have a marked effect on CelRH5 activity. However, the enzyme is quite sensitive to the presence of 10 mM ions Zn2+, Ni2+, Co2+, Fe3+ and reagents such as 1 M guanidine HCl, 0.1% sodium dodecyl sulfate (SDS) and 20% ethanol. Given that it is psychrotolerant and retains activity in the presence of final cellulose degradation products, metal ions and various reagents, which are common in many technological processes; CelRH5 may be potential suitability for a variety of different biotechnological applications.


Physical properties of the E. coli 4.5S RNA: first results suggest a hairpin helix of unusual thermal stability.
Hyperchromicity measurements and quasi-elastic laser light scattering (QELS) have been used to assess the solution structure of the metabolically stable E. coli 4.5S RNA. Results from thermal denaturation measurements revealed the 4.5S species to be markedly more stable than most other RNAs characterized thus far. Optical Tm's range from 79 degrees to 88 degrees with transitions approximately 25 degrees C wide. The Tm values show little dependence on ionic strength, but stability is enhanced considerably by Mg+2. In the QELS experiments the diffusion coefficient does not decrease until T greater than 70 degrees C. Neither the diffusive melting nor the diffusion coefficient at infinite dilution (D0(20,w)) show dependencies on ionic strength but both are influenced by Mg+2. The diffusion behavior is in agreement with that predicted for a rigid cylindrical molecule 125 to 160 A long and 37 to 26 A in diameter. Taken together these results are consistent with the more stable hypothetical secondary structures that can be formed, in which 70-75% of the 114 bases are paired to form a single extended hairpin helix.


Earthquake disasters--lessons to be learned.
Human beings do not have the ability prevent earthquakes. However, we can take measures to minimize injuries and damage by using strict building codes and constructing infrastructures in areas of less risk. A great number of buildings in Israel, including some hospitals, will not withstand a major earthquake as they were built with inadequate standards. Data collected during earthquakes show a significant rise in cardiac-related disease and stress-related medical problems in addition to conventional injuries. Public health issues are of increasing importance due to the collapse of sanitation facilities. In addition to field clinics, field hospitals should be deployed in the vicinity of the stricken area. While planning the medical response for disasters such as earthquakes, one should take into account the availability of local medical personnel. Some or most of the local staff may be unable to function. A study from the Gulf War showed that even the threat of chemical attack resulted in less staff reporting to work [33]. During the 1999 earthquakes in Turkey, many of the hospital staff opted to care for their close families instead of reporting to work at the hospital. Regular training exercises in prehospital emergency medical services for the more common multiple casualty incidents should be bolstered with additional exercises in mass casualty incidents. The basic functions in these scenarios may be quite different. Although no exercise can mimic the real event, preplanning and drills are invaluable. When an earthquake does occur, medical management includes local search and rescue teams together with emergency medical service teams if these can still function. Early deployment of local medical centers can alleviate the burden from local hospitals. Evacuation to distant medical centers is probably a major key for success. Psychological problems are abundant in such incidences, affecting also rescue and medical teams. It becomes a major issue when there are large numbers of pediatric casualties and the operations continue for more than a few days.


Bioactivation of tamoxifen by recombinant human cytochrome p450 enzymes.
Tamoxifen is a major drug used for adjuvant chemotherapy of breast cancer; however, its use has been associated with a small but significant increase in risk of endometrial cancer. In rats, tamoxifen is a hepatocarcinogen, and DNA adducts have been observed in both rat and human tissues. Tamoxifen has been shown previously to be metabolized to reactive products that have the potential to form protein and DNA adducts. Previous studies have suggested a role for P450 3A4 in protein adduct formation in human liver microsomes, via a catechol intermediate; however, no clear correlation was seen between P450 3A4 content of human liver microsomes and adduct formation. In the present study, we investigated the P450 forms responsible for covalent drug-protein adduct formation and the possibility that covalent adduct formation might occur via alternative pathways to catechol formation. Recombinant P450 3A4 catalyzed adduct formation, and this correlated with the level of uncoupling in the P450 incubation, consistent with a role of reactive oxygen species in potentiating adduct formation after enzymatic formation of the catechol metabolite. Whereas P450s 1A1, 2D6, and 3A5 generated catechol metabolite, no covalent adduct formation was observed with these forms. By contrast, P450 2B6, 2C19, and rat liver microsomes catalyzed drug-protein adduct formation but not catechol formation. Drug protein adducts formed specifically with P450 3A4 in incubations using membranes isolated from bacteria expressing P450 3A4 and reductase, as well as in reconstitutions of purified 3A4, suggesting that the electrophilic species reacted preferentially with the P450 enzymes concerned.


Syphilis-related Membranous Nephropathy in a 35-year-old Woman.
A 35-year-old woman was admitted for the examination of lower leg edema and proteinuria. A kidney biopsy showed membranous nephropathy (MN) with fine granular deposits of IgG along the glomerular capillary and poor spike formation, differing from primary MN in the presence of positive IgG3 and C1q. Lupus nephritis was excluded because serum complement and anti-dsDNA antibody, anti-Smith antibody, and anti-cardiolipin antibody tests were negative. The serological test for syphilis was positive, as was the Treponema pallidum hemagglutination test. The patient was diagnosed with syphilis, and the proteinuria disappeared with antibiotic treatment. In MN with positive IgG3 and C1q, syphilis nephropathy may be a differential diagnosis.


Effects of expiratory muscle training on the frail elderly's respiratory function.
[Purpose] The present study examined the effects of expiratory muscle training on elderly day care service users, who had been classified into Care Grades 1 and 2 based on Japan's long-term care insurance system. [Subjects and Methods] Intervention was provided for 29 Care Grade 1 or 2 day care service users. During intervention, expiratory muscle training was performed by slowly expiring using the abdominal muscles and a device after maximal inspiration. Each intervention session lasted for approximately 10 minutes, and 2 sessions were held weekly for 3 months to compare respiratory function test values before and after intervention. [Results] The results were favorable. The vital capacity (VC) and peak expiratory flow (PEF) significantly varied between before and after intervention. [Conclusion] Expiratory muscle training generally improved their respiratory function, particularly their VC and PEF that significantly varied between before and after intervention. As both of these items influence the cough capacity, they may be key to the prevention of aspiration pneumonia. Expiratory muscle training may also contribute to activities of daily living (ADL) and the quality of life, and it is expected to play an important role in rehabilitation as a field of preventive medicine.


Self-organization in a bimotility mixture of model microswimmers.
We study the cooperation and segregation dynamics in a bimotility mixture of microorganisms which swim at low Reynolds numbers via periodic deformations along the body. We employ a multiparticle collision dynamics method to simulate a two component mixture of artificial swimmers, termed as Taylor lines, which differ from each other only in the propulsion speed. The analysis reveals that a contribution of slower swimmers towards clustering, on average, is much larger as compared to the faster ones. We notice distinctive self-organizing dynamics, depending on the percentage difference in the speed of the two kinds. If this difference is large, the faster ones fragment the clusters of the slower ones in order to reach the boundary and form segregated clusters. Contrarily, when it is small, both kinds mix together at first, the faster ones usually leading the cluster and then gradually the slower ones slide out thereby also leading to segregation.


Conformational Behavior of SARS-Cov-2 Spike Protein Variants: Evolutionary Jumps in Sequence Reverberate in Structural Dynamic Differences.
SARS-CoV-2 has evolved rapidly in the first 3 years of pandemic diffusion. The initial evolution of the virus appeared to proceed through big jumps in sequence changes rather than through the stepwise accumulation of point mutations on already established variants. Here, we examine whether this nonlinear mutational process reverberates in variations of the conformational dynamics of the SARS-CoV-2 Spike protein (S-protein), the first point of contact between the virus and the human host. We run extensive microsecond-scale molecular dynamics simulations of seven distinct variants of the protein in their fully glycosylated state and set out to elucidate possible links between the mutational spectrum of the S-protein and the structural dynamics of the respective variant, at global and local levels. The results reveal that mutation-dependent structural and dynamic modulations mostly consist of increased coordinated motions in variants that acquire stability and in an increased internal flexibility in variants that are less stable. Importantly, a limited number of functionally important substructures (the receptor binding domain, in particular) share the same time of movements in all variants, indicating efficient preorganization for functional regions dedicated to host interactions. Our results support a model in which the internal dynamics of the S-proteins from different strains varies in a way that reflects the observed random and non-stepwise jumps in sequence evolution, while conserving the functionally oriented traits of conformational dynamics necessary to support productive interactions with host receptors.


B Chromosome Diversity and Repetitive Sequence Distribution in an Isolated Population of Akodon montensis (Rodentia, Sigmodontinae).
B chromosomes are supernumerary chromosomes found in the karyotypes of approximately 15% of all eukaryotic species. They present parasitic behavior and do not follow the standard Mendelian pattern of inheritance, resulting in an imbalance in gametogenesis. The evolutionary dynamics of B chromosomes is still unknown for many species, but studies indicate that the accumulation of repetitive sequences plays an important role in the differentiation of these elements. We analyzed morphology, frequency, and possible homologies amongst different B chromosomes found in an isolated Akodon montensis population in southern Brazil. Repetitive sequences (18S, 5S rDNA and telomeric sequences) were used to test for their accumulation on the supernumerary chromosomes and describe their localization in the species. The results indicate 4 different B chromosome morphotypes, and DNA libraries were generated for 3 of them. 18S rDNA was labelled polymorphically, except in the B chromosomes, whereas the 5S rDNA was located exclusively in an interstitial position on the long arm of chromosome 5. Chromosome painting with the B probes based on FISH revealed a homologous composition for all B chromosome morphotypes and no homology with the chromosomes in the A complement. B chromosomes found in this population may have a common origin and subsequently diversified in size and morphology.


Biogenic Metal Oxides.
Biogenic metal oxides (MxOy) feature structures as highly functional and unique as the organisms generating them. They have caught the attention of scientists for the development of novel materials by biomimicry. In order to understand how biogenic MxOy could inspire novel technologies, we have reviewed examples of all biogenic MxOy, as well as the current state of understanding of the interactions between the inorganic MxOy and the biological matter they originate from and are connected to. In this review, we first summarize the origins of the precursors that living nature converts into MxOy. From the point-of-view of our materials chemists, we present an overview of the biogenesis of silica, iron and manganese oxides, as the only reported biogenic MxOy to date. These MxOy are found across all five kingdoms (bacteria, protoctista, fungi, plants and animals). We discuss the key molecules involved in the biosynthesis of MxOy, the functionality of the MxOy structures, and the techniques by which the biogenic MxOy can be studied. We close by outlining the biomimetic approaches inspired by biogenic MxOy materials and their challenges, and we point at promising directions for future organic-inorganic materials and their synthesis.


Virtual Reality for Management of Pain in Hospitalized Patients: Results of a Controlled Trial.
Improvements in software and design and reduction in cost have made virtual reality (VR) a practical tool for immersive, three-dimensional (3D), multisensory experiences that distract patients from painful stimuli. The objective of the study was to measure the impact of a onetime 3D VR intervention versus a two-dimensional (2D) distraction video for pain in hospitalized patients. We conducted a comparative cohort study in a large, urban teaching hospital in medical inpatients with an average pain score of ≥3/10 from any cause. Patients with nausea, vomiting, dementia, motion sickness, stroke, seizure, and epilepsy and those placed in isolation were excluded. Patients in the intervention cohort viewed a 3D VR experience designed to reduce pain using the Samsung Gear Oculus VR headset; control patients viewed a high-definition, 2D nature video on a 14-inch bedside screen. Pre- and postintervention pain scores were recorded. Difference-in-difference scores and the proportion achieving a half standard deviation pain response were compared between groups. There were 50 subjects per cohort (N=100). The mean pain reduction in the VR cohort was greater than in controls (-1.3 vs -0.6 points, respectively; P=.008). A total of 35 (65%) patients in the VR cohort achieved a pain response versus 40% of controls (P=.01; number needed to treat=4). No adverse events were reported from VR. Use of VR in hospitalized patients significantly reduces pain versus a control distraction condition. These results indicate that VR is an effective and safe adjunctive therapy for pain management in the acute inpatient setting; future randomized trials should confirm benefit with different visualizations and exposure periods. Clinicaltrials.gov NCT02456987; https://clinicaltrials.gov/ct2/show/NCT02456987 (Archived by WebCite at http://www.webcitation.org/6pJ1P644S).


Ovarian ectopic pregnancy.
The authors report the rare case of a 25-year-old female who suffered from an ovarian ectopic pregnancy. She presented at 10 weeks gestation with a 1-day history of vaginal bleeding and lower abdominal discomfort. β-human chorionic gonadotropin concentration was 8538 IU/ml. Ultrasound showed a right adnexal mass 4.0 × 3.8 × 5.5 cm with a 16 mm cystic area suggesting right ovarian ectopic pregnancy. Diagnostic laparoscopy confirmed a ruptured right ovarian ectopic pregnancy with haemoperitoneum. This was excised laparoscopically. She made a good postoperative recovery and was discharged on the second postoperative day. Histology confirmed a ruptured ovarian ectopic pregnancy. Ovarian ectopic pregnancy is a rare condition. There are two features that make this an unusual case; the relatively late gestation at which she presented and her mild presenting features. Unlike tubal ectopic pregnancies, which usually present at earlier gestations, this patient presented relatively late. She also presented with mild symptoms and signs.


The effects of 1, 2, 3, 4, 10, 10-hexachloro-1, 4, 4a, 5, 8, 8a-hexahydroxy endo, exo-5, 8-dimethionaphthalene (aldrin) and sodium ethylenebisdithiocarbomate (nabam) on the chick.
Fertile White Leghorn chicken eggs were injected on the tenth day of incubation with either 0, 10, 20, 30, 40 or 50 p.p.m. Aldrin or 0, 5, 10 or 15 p.p.m. Nabam and allowed to hatch. Aldrin neither did induce any deformities nor had any effect on hatchability, thyroid weight and histology. However, within three days after hatching, there was greater mortality in chicks treated with higher concentrations of the pesticide. Aldrin at higher concentrations significantly reduced 125I uptake by the thyroids. This was evident in the iodine fractions after chromatographic separation of the thyroid extracts. Nabam not only reduced hatchability but also induced deformities in the higher concentration groups. The thyroids showed an increase of resorption vacuoles in the colloid. Even though the thyroid weights increased in all experimental groups, a significant increase in 125I uptake was seen only in the 15 p.p.m. injected animals. This group also showed a reduction in radioactivity of thyroxine fraction but an increase of 125I in tyrosines. The significance of these results are discussed.


Two new species and new records of Maruina Müller, 1895 (Diptera: Psychodidae) in Brazil.
Two new species of Maruina, Maruina cirrata sp. nov. and Maruina mucugensis sp. nov., collected in two mountainous areas in Bahia, are described and figured. Additionally, we present new records of Maruina guria Bravo, 2004 and M. menina Bravo Lago, 2003 in Brazil.


Xanthogranulomatous Pancreatitis -A Rare Case Defying Clinical, Radiological and Tumor Marker Diagnostics with a Review of Literature.
Xanthogranulomatous inflammation of the pancreas is an extremely rare entity mimicking pancreatic neoplasia. Elevation of tumor markers has seldom been reported in xanthogranulomatous inflammation of the pancreas, rendering the diagnosis difficult and highlighting the importance of a meticulous histopathological examination. A 58-year-old male presented with severe abdominal pain and anorexia for six months. A heterogeneously enhancing solid cystic mass was detected in the pancreatic head on contrast enhanced computed tomography. Endoscopic ultrasound guided aspiration yielded fluid showing elevated levels of CA19-9 (12000 IU/ml) and CEA (221ng/ml) with a concordant increase in the serum tumour marker levels (CA 19-9:407 IU/ml; CEA: 70 ng /ml). Clinical, radiological and biochemical evidence favouring malignancy prompted a Whipple's procedure. A thorough histopathological examination of the specimen failed to reveal malignancy. Sheets of macrophages (CD 68 +, HAM 56 +), chronic inflammatory cells, fibroblasts and proliferating capillaries replacing most of the pancreatic parenchyma were seen instead, nailing the diagnosis of xanthogranulomatous inflammation of the pancreas. To the best of our knowledge this is the first report of xanthogranulomatous inflammation of the pancreas without associated malignancy displaying an elevation of serum and fluid tumour markers. After seven months of follow up, the patient is asymptomatic and is doing well.


Health science libraries of national, state, and local medical organizations.
This second survey of medical society-sponsored libraries has been expanded to include national association libraries in allied medical fields, as well as special libraries which do not fall into categories established for the MLA survey of health science libraries. A total of fifty-eight libraries in this subset have been identified, and selected characteristics have been measured. Observations are made concerning methodology, user population, and services.


The effects of camelina sativa oil and high-intensity interval training on liver function and metabolic outcomes in male type 2 diabetic rats.
The purpose of this study was to evaluate the independent and combined effects of camelina sativa oil and high-intensity interval training (HIIT) on liver function, and metabolic outcomes in streptozotocin-induced diabetic rats. Forty male Wistar rats were randomly assigned to five equal groups (8 per group): Normal control (NC), diabetic control (DC), diabetic + camelina sativa oil (300 mg/kg by oral gavage per day; D + CSO), diabetic + HIIT (running on a treadmill 5 days/week for 8 weeks; D + HIIT), diabetic + camelina sativa oil + HIIT (D + CSO + HIIT). In all three intervention groups (D + CSO, D + HIIT, and D + CSO + HIIT) compared to the DC, hepatic TNF-α, MDA, and histopathology markers, decreased and hepatic PGC-1α, and PPAR-γ increased (p < 0.05). However, the effect of D + CSO was greater than D + HIIT alone. Hepatic TG decreased significantly in D + HIIT and D + CSO + HIIT compared to other groups (p < 0.001). Fasting plasma glucose in all three intervention groups (D + CSO, D + HIIT, and D + CSO + HIIT) and HOMA-IR in D + CSO and D + CSO + HIIT were decreased compared to DC (p < 0.001). Only hepatic TAC and fasting plasma insulin remained unaffected in the three diabetic groups (p < 0.001). Overall, D + CSO + HIIT had the largest effect on all outcomes. At the doses and treatment duration used in the current study, combination of CSO and HIIT was beneficial for reducing liver function and metabolic outcomes other than CSO and HIIT alone.


The hip in the moulded baby syndrome.
The moulded baby syndrome comprises: head moulding (plagiocephaly); pelvic obliquity with unilateral loss of hip abduction in flexion; and occasionally scoliosis, torticollis and bat ears. The hips, however, are radiologically normal and do not require the treatment used in the management of congenital dislocation or dysplasia. A review of 67 hips confirms this finding.


Construct validity of self-reported historical physical activity.
The purpose of this study was to determine the construct-related validity of self-reported historical walking, running, and jogging (WRJ) activity on the basis of data from the Aerobics Center Longitudinal Study (Dallas, Texas). A total of 4,100 men and 963 women underwent at least one medical examination between 1976 and 1985 and completed a follow-up questionnaire in 1986. Levels of glucose, cholesterol, and triglycerides, resting systolic blood pressure, body mass index (weight (kg)/height (m)(2)), and cardiorespiratory fitness were measured at the time of the medical examination. The follow-up questionnaire assessed WRJ and other strenuous activities for each year from 1976 through 1985. Data analysis included Spearman and partial correlations, analysis of variance, analysis of covariance, and t tests. Results indicated significant correlations between recalled WRJ and treadmill times for each year throughout the 10-year period (r = 0.40-0.61). Participants were classified as historically either sufficiently physically active to receive a health benefit or insufficiently active for a health benefit. Engaging in sufficient levels of historical WRJ was associated with higher treadmill times and lower body mass indices for men and women and lower triglyceride levels for men. Self-reported historical WRJ can be assessed with reasonable validity in comparison with measured treadmill performance, with no decay in accuracy of reporting for up to 10 years in the past.


Cysteine residues in signal transduction and its relevance in pancreatic beta cells.
Cysteine is one of the least abundant but most conserved amino acid residues in proteins, playing a role in their structure, metal binding, catalysis, and redox chemistry. Thiols present in cysteines can be modified by post-translational modifications like sulfenylation, acylation, or glutathionylation, regulating protein activity and function and serving as signals. Their modification depends on their position in the structure, surrounding amino acids, solvent accessibility, pH, etc. The most studied modifications are the redox modifications by reactive oxygen, nitrogen, and sulfur species, leading to reversible changes that serve as cell signals or irreversible changes indicating oxidative stress and cell damage. Selected antioxidants undergoing reversible oxidative modifications like peroxiredoxin-thioredoxin system are involved in a redox-relay signaling that can propagate to target proteins. Cysteine thiols can also be modified by acyl moieties' addition (derived from lipid metabolism), resulting in protein functional modification or changes in protein anchoring in the membrane. In this review, we update the current knowledge on cysteine modifications and their consequences in pancreatic β-cells. Because β-cells exhibit well-balanced redox homeostasis, the redox modifications of cysteines here serve primarily for signaling purposes. Similarly, lipid metabolism provides regulatory intermediates that have been shown to be necessary in addition to redox modifications for proper β-cell function and, in particular, for efficient insulin secretion. On the contrary, the excess of reactive oxygen, nitrogen, and sulfur species and the imbalance of lipids under pathological conditions cause irreversible changes and contribute to oxidative stress leading to cell failure and the development of type 2 diabetes.


Sudden death in the laboratory rat.
Vulnerability to sudden death was produced in laboratory rats by manipulating their developmental history. Rats who were reared in isolation died suddenly when placed in a stressful swimming situation. Handling of these singly-housed rats from 25 to 100 days of age potentiated the phenomenon. However, animals who were group housed did not die even when they had been previously handled.


Surgical treatment of bleeding problems in perimenopausal women.
Bleeding problems are common in perimenopausal women. They affect quality of life. Traditionally, hysterectomy was the definitive 'cure'; however, the past two decades have seen the emergence of less invasive and safer alternatives, in the form of endometrial ablation. Like hysterectomy, these treatments have a high satisfaction rate. Endometrial ablation employing resection techniques may be the procedure of choice in perimenopausal women because the majority of the endometrial cavity is sampled, which may reduce the risk of undetected endometrial cancer. Since no operation is without risk, women should be appropriately selected and counselled.


Bronchial hyper-responsiveness after preterm birth.
Being born preterm often adversely affects later lung function. Airway obstruction and bronchial hyperresponsiveness (BHR) are common findings. Respiratory symptoms in asthma and in lung disease after preterm birth might appear similar, but clinical experience and studies indicate that symptoms secondary to preterm birth reflect a separate disease entity. BHR is a defining feature of asthma, but can also be found in other lung disorders and in subjects without respiratory symptoms. We review different methods to assess BHR, and findings reported from studies that have investigated BHR after preterm birth. The area appeared understudied with relatively few and heterogeneous articles identified, and lack of a pervasive understanding. BHR seemed related to low gestational age at delivery and a neonatal history of bronchopulmonary dysplasia. No studies reported associations between BHR after preterm birth and the markers of eosinophilic inflammatory airway responses typically found in asthma. This should be borne in mind when treating preterm born individuals with BHR and airway symptoms.


Dual FISH analysis of benign and malignant tumors of the salivary glands and paranasal sinuses.
To date, the underlying genomic changes in benign and malignant tumors of salivary-gland and paranasal-sinus origin are poorly understood. This is due in part to the low incidence of these tumors and the enormous histological variety of tumors within this head and neck region. We examined 58 of these tumors (14 adenoid cystic carcinomas, 9 adenocarcinomas, 5 cylindrical carcinomas, 11 pleomorphic adenomas, and 19 inverted papillomas) by dual fluorescence in situ hybridization (FISH) with centromere-specific probes on six chromosomes (3, 7, 9, 11, 17, and 18) for numerical changes. In adenoid cystic carcinomas, monosomy of chromosome 17 and polysomy of chromosomes 3, 9 and 11 were most frequently encountered. In adenocarcinomas, monosomy of chromosome 17 and polysomy of chromosomes 7 and 11 were most frequent. In cylindrical cell carcinomas, polysomy of chromosomes 7, 9, 11 and 17 was present in the majority of tumors. Disomy is rare, even in benign tumors. Polysomy is more frequent in malignant tumors than in benign. Tetrasomy is found almost only in malignant tumors. In summary, the occurrence of polysomy might reflect a step towards malignancy in tumors of the salivary glands and paranasal mucosa. Polysomy of chromosome 11 could be defined as typical for all investigated histological types of malignant tumor in this region of the head and neck.


Polymeric Materials Selection for Flexible Pulsating Heat Pipe Manufacturing Using a Comparative Hybrid MCDM Approach.
The right choice of polymeric materials plays a vital role in the successful design and manufacture of flexible fluidic systems, as well as heat transfer devices such as pulsating heat pipes. The decision to choose an acceptable polymeric material entails a variety of evaluation criteria because there are numerous competing materials available today, each with its own properties, applications, benefits, and drawbacks. In this study, a comparative hybrid multi-criteria decision-making (MCDM) model is proposed for evaluating suitable polymeric materials for the fabrication of flexible pulsating heat pipes. The decision model consists of fourteen evaluation criteria and twelve alternative materials. For this purpose, three different hybrid MCDM methods were applied to solve the material selection problems (i.e., AHP-GRA, AHP-CoCoSo, and AHP-VIKOR). According to the results obtained, PTFE, PE, and PP showed promising properties. In addition, Spearman's rank correlation analysis was performed, and the hybrid methods used produced consistent rankings with each other. By applying MCDM methods, it was concluded that PTFE is the most suitable material to be preferred for manufacturing flexible pulsating heat pipes. In addition to this result, PE and PP are among the best alternatives that can be recommended after PTFE. The study supports the use of MCDM techniques to rank material choices and enhance the selection procedure. The research will greatly assist industrial managers and academics involved in the selection process of polymeric materials.


The cytokines interleukin-1β and tumor necrosis factor-α stimulate CFTR-mediated fluid secretion by swine airway submucosal glands.
The airway is kept sterile by an efficient innate defense mechanism. The cornerstone of airway defense is mucus containing diverse antimicrobial factors that kill or inactivate pathogens. Most of the mucus in the upper airways is secreted by airway submucosal glands. In patients with cystic fibrosis (CF), airway defense fails and the lungs are colonized by bacteria, usually Pseudomonas aeruginosa. Accumulating evidence suggests that airway submucosal glands contribute to CF pathogenesis by failing to respond appropriately to inhalation of bacteria. However, the regulation of submucosal glands by the innate immune system remains poorly understood. We studied the response of submucosal glands to the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α. These are released into the airway submucosa in response to infection with the bacterium P. aeruginosa and are elevated in CF airways. Stimulation with IL-1β and TNF-α increased submucosal gland secretion in a concentration-dependent manner with a maximal secretion rate of 240 ± 20 and 190 ± 40 pl/min, respectively. The half maximal effective concentrations were 11 and 20 ng/ml, respectively. The cytokine effect was dependent on cAMP but was independent of cGMP, nitric oxide, Ca(2+), or p38 MAP kinase. Most importantly, IL-1β- and TNF-α-stimulated secretion was blocked by the CF transmembrane conductance regulator (CFTR) blocker, CFTRinh172 (100 μmol/l) but was not affected by the Ca(2+)-activated Cl(-) channel blocker, niflumic acid (1 μmol/l). The data suggest, that during bacterial infections and resulting release of proinflammatory cytokines, the glands are stimulated to secrete fluid, and this response is mediated by cAMP-activated CFTR, a process that would fail in patients with CF.


Clinical outcomes of ambulatory acute exacerbations of chronic bronchitis with older versus newer antimicrobials.
To determine whether the cure rate was similar between traditional and newer antibiotics in the treatment of acute exacerbations of chronic bronchitis (AECB), to determine whether antibiotic selection during the first AECB of the season influences the frequency of subsequent AECB, and to identify variables associated with poor short- and long-term treatment outcome. A retrospective analysis of subjects seen for management of their first seasonal AECB was conducted. Subjects were stratified into traditional therapies (n = 95) or newer therapies (n = 101) by antibiotic prescription. There was no difference in initial cure rates between older versus newer antibiotics (93% vs. 95%; p = 0.48). There was no difference in the number of subjects that remained AECB-free for 6 months after initial treatment with older versus newer antibiotic regimens (34% vs. 28%; p = 0.37). Oxygen initiation or increased dose (OR 10.9; 95% CI 1.4 to 84.2; p = 0.02) was the only variable independently associated with lack of AECB resolution. Nonsmoking status trended toward an association with remaining AECB-free at 180 days (OR 0.39; 95% CI 0.15 to 1.01; p = 0.053). The use of older versus newer antibiotics did not independently predict short-term outcome or future AECB.


Spectroscopic Discrimination of Diastereomeric Complexes Involving an Axially Chiral Receptor.
The infrared multiphoton dissociation (IRMPD) spectra of electrospray ionization (ESI)-formed proton-bound complexes between the axially chiral multifunctional macrocycle MaR and d- and l-phenylalanine (PD and PL ) or d- and l-3,4-dihydroxyphenylalanine (DD and DL ) are recorded in the ν˜ =2800-3700 cm-1 region. Whereas the diastereomeric [MaR ⋅H⋅PD ]+ and [MaR ⋅H⋅PL ]+ complexes do not show any significant spectral differences, the spectrum of [MaR ⋅H⋅DD ]+ clearly diverges from that of its [MaR ⋅H⋅DL ]+ diastereomer. A comparison of the experimental spectra with the B3LYP/6-31G**-calculated harmonic vibrational frequencies of a number of stable structures indicates the formation, in the ESI source, of very similar spectroscopically active structures, with the protonated amino acid placed outside the flat cavity of the macrocycle and hydrogen-bonded at its O2 center. Different spectral signatures of the [MaR ⋅H⋅DD ]+ and [MaR ⋅H⋅DL ]+ complexes are attributed to the coexistence of several stable rotamers in the ESI source.


Demographics, Preventive Services Compliance, Health, and Healthcare Experiences of Lesbian, Gay, and Bisexual Employed Adults.
This study examined demographics, health risks and conditions, preventive services, and health care experiences of lesbian, gay, bisexual, transgender, or questioning (LGBTQ) adults who are employed in the United States. Male and female gay, lesbian, or bisexual employees (N = 1191) from seven companies participated in an online survey. Differences were observed in the characteristics of gays, lesbians, and bisexuals on a number of demographic, health, and preventive services measures. Differences were also seen compared to previous studies about LGBTQ adults in the general population. Employers have a vested interest in making sure their employees have access to quality health care that addresses their unique needs. There is much room for improvement in this area, since a large percentage of respondents reported negative health care experiences, avoiding or postponing care, and difficulty finding an LGBTQ-experienced healthcare provider.


Current nervous system related drug targets for the treatment of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a debilitating and ultimately fatal indication that is the most prevalent adult-onset motoneuron disorder. ALS imparts tremendous suffering upon patients and caregivers alike. Exciting new insight has been obtained as to the etiology and initiation of the disease during the past decade, particularly affecting the larger, sporadic patient population. An important new discovery is the involvement of the TAR DNA binding protein (TDP-43) based upon genetic evidence and the presence of the cytosolic ubiquitylated TDP-43 aggregates found during post-mortem analysis of damaged motoneurons in the spinal cord of ALS patients. Superoxide dismutase SOD1 continues to be of interest for the approximately 20% of the familial ALS patients who have the inherited form of the disease ( approximately 15% of the total), but SOD1 does not appear to be as relevant as was once imagined for the sporadic patent population. We can now target specific biochemical pathways and deficits via traditional drug discovery efforts and may thus be able to achieve more effective therapeutic relief for patients who suffer from this disease. In this review we present a comprehensive discussion of current molecular targets and pathways that are of interest to small molecule drug discovery efforts for the treatment of ALS.


Investigation of two yeast genes encoding putative isoenzymes of phosphoglycerate mutase.
Our previous data indicated that GPM1 encodes the only functional phosphoglycerate mutase in yeast. However, in the course of the yeast genome sequencing project, two homologous sequences, designated GPM2 and GPM3, were detected. They have been further investigated in this work. Key residues in the deduced amino acid sequence, shown to be involved in catalysis for Gpm1 (i.e. His8, Arg59, His181) are conserved in both enzymes. Overexpression of the genes under control of their own promoters in a gpm1 deletion mutant did not complement for any of the phenotypes. This could in part be attributed to a lack of expression due to their weak promoters. Higher level expression under the control of the yeast PFK2 promoter partially complemented the gpm1 defects, without restoring detectable enzymatic activity. Nevertheless, deletion of either GPM2 or GPM3, or the two deletions in concert, did not produce any obvious lesions for growth on a variety of different carbon sources, nor did they change the levels of key intermediary metabolites. We conclude that both genes evolved from duplication events and that they probably constitute non-functional homologues in yeast.


Genome Wide Analysis of Nucleotide-Binding Site Disease Resistance Genes in Brachypodium distachyon.
Nucleotide-binding site (NBS) disease resistance genes play an important role in defending plants from a variety of pathogens and insect pests. Many R-genes have been identified in various plant species. However, little is known about the NBS-encoding genes in Brachypodium distachyon. In this study, using computational analysis of the B. distachyon genome, we identified 126 regular NBS-encoding genes and characterized them on the bases of structural diversity, conserved protein motifs, chromosomal locations, gene duplications, promoter region, and phylogenetic relationships. EST hits and full-length cDNA sequences (from Brachypodium database) of 126 R-like candidates supported their existence. Based on the occurrence of conserved protein motifs such as coiled-coil (CC), NBS, leucine-rich repeat (LRR), these regular NBS-LRR genes were classified into four subgroups: CC-NBS-LRR, NBS-LRR, CC-NBS, and X-NBS. Further expression analysis of the regular NBS-encoding genes in Brachypodium database revealed that these genes are expressed in a wide range of libraries, including those constructed from various developmental stages, tissue types, and drought challenged or nonchallenged tissue.


Remote histology learning from static versus dynamic microscopic images.
Histology is the study of microscopic structures in normal tissue sections. Curriculum redesign in medicine has led to a decrease in the use of optical microscopes during practical classes. Other imaging solutions have been implemented to facilitate remote learning. With advancements in imaging technologies, learning material can now be digitized. Digitized microscopy images can be presented in either a static or dynamic format. This study of remote histology education identifies whether dynamic pictures are superior to static images for the acquisition of histological knowledge. Test results of two cohorts of second-year Bachelor in Medicine students at Ghent University were analyzed in two consecutive academic years: Cohort 1 (n = 190) and Cohort 2 (n = 174). Students in Cohort 1 worked with static images whereas students in Cohort 2 were presented with dynamic images. ANCOVA was applied to study differences in microscopy performance scores between the two cohorts, taking into account any possible initial differences in prior knowledge. The results show that practical histology scores are significantly higher with dynamic images as compared to static images (F (1,361) = 15.14, P < 0.01), regardless of student's gender and performance level. Several reasons for this finding can be explained in accordance with cognitivist learning theory. Since the findings suggest that knowledge construction with dynamic pictures is stronger as compared to static images, dynamic images should be introduced in a remote setting for microscopy education. Further implementation within a larger electronic learning management system needs to be explored in future research. Anat Sci Educ 9: 222-230. © 2015 American Association of Anatomists.


GENETIC COVARIANCE OF FITNESS CORRELATES: WHAT GENETIC CORRELATIONS ARE MADE OF AND WHY IT MATTERS.
The genetic variance-covariance matrix, G, is determined in part by functional architecture, the pathways by which variation in genotype influences phenotype. I develop a simple architectural model for G for two traits under directional selection constrained by their dependence on a common limiting resource. I assume that genetic variance is maintained by mutation-selection balance. The relative numbers of loci that play a role in acquiring versus allocating a limiting resource play a crucial role in determining genetic covariance. If many loci are involved in acquiring a resource, genetic covariance may be either negative or positive at equilibrium, depending on the fitness function and the input of mutational variance. The form of G does not necessarily reveal the constraint on resource acquisition inherent in the system, and therefore studies estimating G do not test for the existence of life-history tradeoffs. Characters may evolve in patterns that are unpredictable from G. Experiments are suggested that would indicate if this model could explain observations of positive genetic covariance.


Peptides derived from dolicholin, a phaseolin-like protein in country beans (Dolichos lablab), potently stimulate cholecystokinin secretion from enteroendocrine STC-1 cells.
Peptides derived from soybean beta-conglycinin and pork protein stimulate cholecystokinin (CCK) secretion from the enteroendocrine cells (EECs) and suppress food intake. Here we examined CCK-releasing activities from the enteroendocrine cell line STC-1, in peptides derived from underutilized legumes, and found much higher activity in the peptic hydrolysate of Country beans (CBP) compared to that from other legume-derived peptides including beta-conglycinin peptone. Active components in CBP were separated into acetonitrile-soluble fractions, but the activities were abolished after pronase treatment. To identify the Country bean protein containing the active peptides, Country bean protein extracts in an alkaline solution (CBE) were fractionated based on isoelectric point or molecular weight. Peptones prepared from CBE fractions containing a 51 kDa major protein stimulated CCK release, but other fractions did not. N-Terminal sequence analysis indicated that the 51 kDa protein is a phaseolin-like globular protein, and we designated this protein dolicholin. These results indicate that Country bean-derived peptides are very potent legume peptides in stimulating CCK secretion from EECs and that the stimulant peptides originate from dolicholin, a newly identified phaseolin-like globular protein in Country beans.


Prediction of morbidity and mortality after early cholecystectomy for acute calculous cholecystitis: results of the S.P.Ri.M.A.C.C. study.
Less invasive alternatives than early cholecystectomy (EC) for acute calculous cholecystitis (ACC) treatment have been spreading in recent years. We still lack a reliable tool to select high-risk patients who could benefit from these alternatives. Our study aimed to prospectively validate the Chole-risk score in predicting postoperative complications in patients undergoing EC for ACC compared with other preoperative risk prediction models. The S.P.Ri.M.A.C.C. study is a World Society of Emergency Surgery prospective multicenter observational study. From 1st September 2021 to 1st September 2022, 1253 consecutive patients admitted in 79 centers were included. The inclusion criteria were a diagnosis of ACC and to be a candidate for EC. A Cochran-Armitage test of the trend was run to determine whether a linear correlation existed between the Chole-risk score and a complicated postoperative course. To assess the accuracy of the analyzed prediction models-POSSUM Physiological Score (PS), modified Frailty Index, Charlson Comorbidity Index, American Society of Anesthesiologist score (ASA), APACHE II score, and ACC severity grade-receiver operating characteristic (ROC) curves were generated. The area under the ROC curve (AUC) was used to compare the diagnostic abilities. A 30-day major morbidity of 6.6% and 30-day mortality of 1.1% were found. Chole-risk was validated, but POSSUM PS was the best risk prediction model for a complicated course after EC for ACC (in-hospital mortality: AUC 0.94, p < 0.001; 30-day mortality: AUC 0.94, p < 0.001; in-hospital major morbidity: AUC 0.73, p < 0.001; 30-day major morbidity: AUC 0.70, p < 0.001). POSSUM PS with a cutoff of 25 (defined in our study as a 'Chole-POSSUM' score) was then validated in a separate cohort of patients. It showed a 100% sensitivity and a 100% negative predictive value for mortality and a 96-97% negative predictive value for major complications. The Chole-risk score was externally validated, but the CHOLE-POSSUM stands as a more accurate prediction model. CHOLE-POSSUM is a reliable tool to stratify patients with ACC into a low-risk group that may represent a safe EC candidate, and a high-risk group, where new minimally invasive endoscopic techniques may find the most useful field of action. ClinicalTrial.gov NCT04995380.


Low risk of bacteremia in children with febrile seizures.
To evaluate the risk of bacteremia in children with febrile seizures treated as outpatients. A retrospective cohort study was performed involving 379 children aged 2 to 24 months presenting to an urban tertiary care children's hospital emergency department with a febrile seizure between February 1, 1993, and May 31, 1996. The mean patient age was 15.9 months, and 217 (57%) were male. In 40 patients (10.6%), the use of oral antibiotics before initial emergency department evaluation was reported. Bacteremia occurred in 8 (2.1%) of 379 children studied. None of the children with bacteremia had received previous antibiotics. The causative organisms were Streptococcus pneumoniae in 7 cases and group A Streptococcus in 1 case. There were 5 contaminated cultures (1.3%). Although 2 of the 8 children with bacteremia ultimately required admission, there were no serious adverse outcomes. Six of 7 episodes of S pneumoniae bacteremia were caused by serotypes included in the pneumococcal conjugate vaccine, which was not available at the time of this study. Children 2 to 24 months of age with febrile seizures are at similar risk for occult bacteremia as those with fever alone. Widespread use of the pneumococcal conjugate vaccine may further decrease the incidence of bacteremia in this population.


Universality in the pair contact process with diffusion.
The pair contact process with diffusion is studied by means of multispin Monte Carlo simulations and density matrix renormalization group calculations. Effective critical exponents are found to behave nonmonotonically as functions of time or of system length and extrapolate asymptotically towards values consistent with the directed percolation universality class. We argue that an intermediate regime exists where the effective critical dynamics resembles that of a parity conserving process.


Analytical study of heavy metals of industrial effluents at Jaipur, Rajasthan (India).
Heavy metals contamination has been recognized as a major environmental concern due to their pervasiveness and persistence. These heavy metals are not biodegradable, hence there is a need to develop such a remediation technique, which should be efficient, economical and rapidly deployable in a wide range of physical settings. For the characterization of heavy metals of various industrial effluents, some heavy metals, like Arsenic, Cadmium, Chromium, Copper, Iron, Manganese, Nickel, Lead and Zinc were analyzed. The results exhibited that As, Cd, Cr and Pb were not found in any studied wastewater samples, while some of the following heavy metals ranged from: Cu (0.0 - 1.0 mg/L), Fe (0.1 - 0.4 mg/L), Mn (0.0 - 0.4 mg/L), Ni (0.01 - 0.07 mg/L) and Zn (0.68 - 60.84 mg/L). Copper, Iron, Manganese and Zinc were found above the standard limit recommended by IS: 3307 (1977). However, Nickel was found below the regulated safety values for all studied samples.


[The role of the food industry in dietetic therapy of the population. Specialized confectionery diabetic food].
Diabetes mellitus is a serious health and social problem of modernity, which in the future will increase and experts predict that the number of patients in 2030 will exceed 438,4 million. Taking into account the seriousness of the problem, and the fact that diabetes hurts an increasing number of young adults, the problem of creating diabetic food products, the positive effect of which on the organism is confirmed by experimental and clinical studies, is very relevant. The overview briefly covers information about the role of diet and ways to modify the composition and formulations of confectionery products of industrial production. The results of industry work towards the development of diabetic confectionery products in Russian Federation and peculiarities of their production and implementation in the framework of the Customs Union countries are summarized. Monitoring of the information entered in the register of specialized food products has been carried out, the lack of common approaches and tools in regulation imposed on the diabetic products in Russia, Belarus and Kazakhstan has been revealed. The necessity of objective regulatory impact assessment has been established. Its results will form the basis of the development of a unified approach to the production, handling and identification of diabetic confectionery and of the introduction of the General principle in relation to the probative value of the data, confirming their quality and safety. To improve the quality of population life and to reduce losses from socially significant diseases is possible through the development of personalized diets and their filling with products with attractive sensory properties. These data indicate the need for training highly qualified specialists with interdisciplinary knowledge in the field of food technology, nutrition and medicine.


Interactions between body size, abundance, seasonality, and phenology in forest beetles.
Body size correlates with a large number of species traits, and these relationships have frequently been used to explain patterns in populations, communities, and ecosystems. However, diverging patterns occur, and there is a need for more data on different taxa at different scales. Using a large dataset of 155,418 individual beetles from 588 species collected over 13 years of sampling in Norway, we have explored whether body size predicts abundance, seasonality, and phenology in insects. Seasonality is estimated here by flight activity period length and phenology by peak activity. We develop several methods to estimate these traits from low-resolution sampling data. The relationship between abundance and body size was significant and as expected; the smaller species were more abundant. However, smaller species tended to fly for longer periods of the summer and peaked in midsummer, while larger species were restricted to shorter temporal windows. Further analysis of repeated sampling from a single location suggested that smaller species had increased flight period lengths in warmer years, but larger species showed the opposite pattern. The results 1) indicate that smaller species are likely to be disproportionately valuable in ecological interactions, and 2) provide potential insights into the traits influencing the vulnerability of some larger species to disturbances and climate change.


Immunochemical analysis of monoclonal antibodies to human erythropoietin.
We recently reported the development of three monoclonal antibodies (MoAbs) to biologically active human erythropoietin (Ep). In the present study, we investigated the epitope specificity of these three antibodies, as well as their reactivity with Eps derived from species other than man. All three antibodies reacted with the Ep polypeptide itself, rather than with its carbohydrate moieties. Moreover, all three antibodies recognized separate nonoverlapping epitopes. Further studies with reduced/alkylated Ep and with sodium dodecyl sulfate-denatured Ep suggested that two of the MoAbs, anti-Ep-2 and anti-Ep-16, were specific for conformational, nonlinear determinants on the Ep molecule, whereas the third MoAb, anti-Ep-26, appeared to recognize a linear epitope. However, anti-Ep-26 did not react with synthetic peptides representing the 26 amino-, the 99-129 mid-region, or the 10 carboxy-terminal residues of Ep, nor with trypsin-, chymotrypsin-, or V8 protease-digested fragments of Ep. When tested with Ep from different species, the neutralizing capabilities of the three MoAbs were clearly different. Comparing their effectiveness against baboon, ovine and murine Ep, antibody 2 was most effective at neutralizing baboon Ep, antibody 16 was most effective against murine Ep, and antibody 26 showed little reactivity with any of these nonhuman Eps. Because these various Eps readily stimulate across species barriers, it is likely that the receptor binding domain on Ep has remained relatively conserved during evolution. Our results therefore suggest that the neutralizing capacity of our three anti-Ep MoAbs is caused not by binding directly to the Ep receptor binding domain on Ep, but by binding to distant regions, causing conformational changes in Ep, or by binding to regions close to the binding site, steric hindrance.


[Serum beta-2-microglobulin in multiple myeloma. Practical value].
The concentration of serum, beta-2-microglobulin (S beta 2m) and the ratio measured S 2m/theoretical S beta 2m M/TH were evaluated in 69 patients with multiple myeloma (MM) and compared with healthy subjects and with patients with a benign monoclonal gammapathy. The concentration of S beta 2m and the ratio S beta 2m M/TH are higher in multiple myeloma than in controls and are strongly correlated with the plasma cell mass On the other hand, no difference was noted concerning the S beta 2m and the ration S beta 2m M/TH between benign monoclonal gammopathy and multiple myeloma at stage I of Durie and Salmon. Under chemotherapy, the variations in concentrations of S beta 2m and of the ratio S beta 2m M/TH are strongly correlated with those of the tumour mass. Beta 2m is not very useful for the differential diagnosis between benign monoclonal gammapathy and multiple myeloma. Beta 2m is very useful in the prognosis of MM, permitting one to assess accurately the tumour mass and the response to treatment, particularly in cases of deficiency of the usual markers.


High rate of complications following volar plating of distal radius fractures.
Fracture of the distal radius (DRF) is one of the most common fractures treated by orthopaedic surgeons. The most common operative treatments of these fractures are open reduction and internal fixation. The incidents and types of complications associated with the use of these operations have not been studied in detail. We performed a retrospective study documenting types of complications and their occurrence in a group of patients who received open reduction and internal fixation. Our definition of a complication was a case in which the patient had one or more complications which required an operation, or suffered from complex regional pain syndrome, or skin healing problems lasting more than four weeks from the operation. A total of 165 patients were included. In all, 39 complications in 30 wrists were registered: i.e. 18% had a minimum of one complication. Our finding that 18% suffer from a serious complication when treated using a volar locking plate must be taken into consideration when surgeons choose between conservative or operative treatment for DRF treatment. A few other studies have looked at the incidents of complications and have reported similar results. not relevant. not relevant.


Effects of growth hormone on tissue metabolism in broiler chicks.
1. The effect of bovine growth hormone (GH) on cartilage, liver, muscle, pancreas and spleen has been investigated. 2. Tissue RNA was elevated in the liver, muscle and spleen of the GH-treated chicks while uptake of radioactive phosphate into RNA was stimulated for both liver and spleen. 3. The GH-treated chicks had an increased cartilage protein content together with a higher rate of incorporation of 14C-methionine pancreatic protein.


Role of three-phase solvent system in the counter-current chromatography.
In counter-current chromatography, the separation efficiency greatly depends on the partitioning ability of the separated substance between the stationary phase and the mobile phase. Partitioning ability is mainly represented by the parameter partition coefficient which is one of the important parameters to evaluate the separation effect of counter-current chromatography. The scope of the partition coefficient value mainly depends on the solvent system. A suitable solvent system election is, therefore, a critical role in the separation of counter-current chromatography. The existing solvent systems that are widely used are mainly two-phase solvent systems. It is difficult to decide on an appropriate solvent system for the separation of compounds with a wide polarity range, which promotes the development of the three-phase solvent system in counter-current chromatography. This review mainly described the origin, development history of three-phase solvent system, summarized the volume ratios and volume fractions of the upper, middle, and lower phases of nearly 50 three-phase solvent systems, their advantages, and disadvantages in counter-current chromatography. In addition, the challenges and future perspectives on three-phase solvent systems in counter-current chromatography also are discussed in this review.


GP 'grand round' - a hospital tradition modified for general practice.
The hospital 'grand round' concept was applied to a general practice continuing professional development activity. Interactive learning sessions were developed to deliver evidence based medicine clinical education for general practitioners and general practice learners (registrars/medical students). The acceptability of the GP grand round format was examined through analysis of participant responses to learning objectives. The article explores some of the issues associated with delivery of small group case based discussion. Evaluations demonstrated that participants in the grand round valued the opportunity to interact with other participants in a small group format, exchanged and shared knowledge and had their learning needs met. The overall quality of the learning experience for the majority of participants was either good or excellent. The application of vertically integrated continuing professional development through a grand round format appears acceptable and effective.


Particle toxicology: from coal mining to nanotechnology.
Particle research has been historically closely connected to industrial activities or materials, such as coal, asbestos, man-made mineral fibers, and more recently ambient particulate matter (PM). It is the purpose of this review to combine insights and developments in particle toxicology with the historical context of exposure and organizations sponsoring such research in Europe. In supporting research on particle-induced respiratory effects and mechanisms, research programs of the European Community on Steel and Coal (ECSC) have played a tremendous role. Current particle research in Europe is dominated by PM, and funded by the World Health Organization (WHO), European Union Framework programs, and the Health Effects Institute (HEI). Differences between historical and current research in particle toxicology include the exposure concentrations, particle size, target populations, endpoints, and length of exposure. Inhaled particle effects are no longer confined to the lung, since particles are suggested to translocate to the blood while lung inflammation invokes systemic responses. Finally, the particle size and concentrations have both been reduced about 100-fold from 2-5 mg/m3 to 20-50 mg/m3 and from 1-2 microm to 20-100 nm (ultrafine) as domestic fuel burning has decreased and vehicle sources have increased and attention has moved from coal mining industry to general environment. There is, however, a further occupational link to nanotechnology, which continuously produces new materials in the ultrafine range. Although inhalation exposure is considered to be minimal in this technology, some particles are produced to be used for carrier purpose in medical applications. Based on our current knowledge of particle toxicology, it is highly desirable that toxicology and technology are linked in this extremely rapid developing area, to learn more about potential risks and also to develop knowledge on the role of surface and size in particle toxicity.


Participatory Action Research With Older Adults: A Critical Interpretive Synthesis.
Given population aging, the meaningful involvement of older adults in influencing policy and programs through participatory action research (PAR) is increasingly vital. PAR holds promise for equitable participation, co-learning, community mobilization, and personal and social transformation, however, little scholarly attention has been given to critically evaluating how PAR has been taken up with older adults. The objective of this review was to critically evaluate the use of PAR with older adults. A critical interpretive synthesis (CIS) of 40 PAR studies with older adults was conducted. Critical engagement with the articles identified dominant tendencies, limits of these tendencies, and proposed ways forward. Within the majority of articles reviewed, older adults were not prominent partners in PAR given their often limited involvement in designing the research questions, learning research skills and knowledge, and implementing findings for change. Furthermore, power differentials between researchers and older adults were evident, as older adults were often positioned as participants rather than partners. Finally, this article demonstrates various boundaries on the foci of studies related to inclusivity and sustainability. This study revealed that the promises PAR holds are often not fully realized in projects with older adults, given that they are rarely positioned as equitable partners, co-learners, or agents for change. The findings have the potential to stimulate further uptake of PAR research with an older adult population, highlighting areas for change in systems and research practices.


[Data standards, terminology and classification systems for caring in health and nursing].
Information is essential for nursing care because nurses in subsidizing clinical decision making for the resolution and reduction of health problems. This review integrative study identified publications in national and international journals the major data standards, terminologies and classification systems used in health care and nursing. The research was conducted on MEDLINE, CINAHL and SCIELO using the keywords: Information Systems, Nursing Informatics, Medical Informatics, Computerized Medical Records Systems, Terminology and Nomenclature of Medicine Systematized. It was selected 91 articles which were analyzed in two empirical categories: "data standards for health care and nursing" and "terminologies and classification systems in nursing" From the various data standards, terminologies and classification systems, it is important that nursing take ownership of them aiming to improve and renew the quality of care.


Synthesis and biological activity of a destruxin analogue: D-Lac-6 destruxin E.
A general strategy for the synthesis of destruxin analogues is described and applied to a particular example, D-Lac-6 destruxin E. The tetrapeptide Boc-Ile-N-MeVal-N-MeAla-beta-Ala-OMe (2) was chosen as the basic starting compound, and its preparation was optimized. This fragment was then coupled with the compound (D)Lac-Pro, and the resulting peptide was cyclized by the DEPC or DPPA/HOBt/DMAP methods at 21 and 30% yield, respectively. The biological activity of the analogue obtained was established by injection to an insect host.


Depo-Provera (depot medroxyprogesterone acetate) use after bariatric surgery.
In the US, obesity rates are increasing greatly. The Centers for Disease Control and Prevention estimates that 68.5% of Americans, including 63.9% of adult women older than 20 years, are overweight (body mass index between 25 kg/m2 and 29.9 kg/m2) or obese (body mass index >30 kg/m2). In light of this, it is not surprising that the rates of bariatric surgery have also been increasing. When considering the metabolic changes associated with both bariatric surgery and contraceptive use, in combination with the unique medical considerations of obese women, it is indisputable that clear guidelines are needed when counseling obese patients of reproductive age after bariatric surgery. In this literature review, we focus on depot medroxyprogesterone acetate (DMPA) and the implications of its use in obese women, preweight and postweight loss following bariatric surgery. Both DMPA use and bariatric surgery are known to cause bone loss, but it is still unclear whether there is an additive effect of the two factors on bone loss and whether either of these factors directly leads to an increased risk of bone fracture. The current consensus guidelines do not impose a restriction on the use of DMPA after bariatric surgery. DMPA use is associated with weight gain, and it is unclear whether weight loss blunting occurs with the use of DMPA after bariatric surgery. Prior studies had demonstrated an association with weight gain in adolescents, and therefore, those prescribing DMPA use after bariatric surgery in adolescents should proceed with caution. Adult women do not have a similar response to the use of DMPA. DMPA use has rarely been associated with increased risk of venous thromboembolism (VTE). The obesity-associated increase in VTE should be mitigated by surgically induced weight loss. The concurrent use of DMPA in the post bariatric surgical period should not further increase the risk of VTE.


Anandamide reduces infarct size in rat isolated hearts subjected to ischaemia-reperfusion by a novel cannabinoid mechanism.
Although the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide share a similar pharmacology, 2-AG reportedly limits myocardial ischaemia-reperfusion injury whereas anandamide does not. We therefore investigated whether or not anandamide reduces infarct size and which, if any, of the known cannabinoid-signalling pathways are involved. Rat isolated perfused hearts were subjected to global, no-flow ischaemia (30 min) and reperfusion (1 h). Agonists were present from 5 min before ischaemia until the end of reperfusion. Antagonists, where used, were present throughout the protocol. Recovery of left ventricular developed pressure and coronary flow was incomplete in control hearts and not significantly affected by any drug treatment. In vehicle-treated hearts, 26+/-3% (n=13) of the left ventricle was infarcted at the end of reperfusion. Infarction of the left ventricle was significantly reduced after 1 microM anandamide (10+/-1%, n=7) or 1 microM methanandamide (12+/-4%, n=6) but not 1 microM HU210. Neither ACPA (1 microM; CB1 receptor agonist) nor JWH133 (1 microM; CB2 receptor agonist), individually or combined significantly affected infarct size. Anandamide (1 microM) did not reduce infarct size in the presence of the CB1 receptor antagonist rimonabant (SR141716A, 1 microM) or the CB2 receptor antagonist, SR144528 (1 microM). Despite sensitivity to CB1 and CB2 receptor antagonists, the infarct-limiting action of anandamide was not mimicked by agonists selective for CB1 or CB2 receptors suggesting the involvement of a novel cannabinoid site of action.


Reactive site in human alpha 2-macroglobulin: circumstantial evidence for a thiolester.
The reaction of methylamine with alpha 2-macroglobulin (alpha 2M) results in the covalent modification of one glutamic residue per subunit as gamma-glutamylmethylamide [Swenson, R. & Howard, J. B. (1979) Proc. Natl. Acad. Sci. USA 76, 4313--4316]. Furthermore, alpha 2M can undergo specific peptide autolysis involving the same reactive glutamic residue [Howard, J. B., Vermeulen, M. & Swenson, R. (1980) J. Biol Chem. 255, 3820--3823]. During both reactions, a cysteinyl thiol is exposed and can be alkylated by iodoacetic acid. After alpha 2M was modified with [14C]methylamine and iodo[2-3H]acetic acid, a tryptic peptide was isolated that contained both labels in the same ratio as in the original protein. From the chymotryptic digest of the tryptic peptide, a single radiolabeled peptide was isolated. The amino acid sequence of the chymotryptic peptide was the same as that previously reported to include gamma-glutamylmethylamide. This is circumstantial evidence for a thiolester between the cysteine and a glutamic acid located three residues away in the primary sequence. A reaction mechanism involving a pyroglutamyl intermediate derived from the thiolester is suggested to explain the autolysis. Kinetic analysis of the autolysis reaction is consistent with this intermediate and mechanism.


TGF-β inhibits alveolar protein transport by promoting shedding, regulated intramembrane proteolysis, and transcriptional downregulation of megalin.
Disruption of the alveolar-capillary barrier is a hallmark of acute respiratory distress syndrome (ARDS) that leads to the accumulation of protein-rich edema in the alveolar space, often resulting in comparable protein concentrations in alveolar edema and plasma and causing deleterious remodeling. Patients who survive ARDS have approximately three times lower protein concentrations in the alveolar edema than nonsurvivors; thus the ability to remove excess protein from the alveolar space may be critical for a positive outcome. We have recently shown that clearance of albumin from the alveolar space is mediated by megalin, a 600-kDa transmembrane endocytic receptor and member of the low-density lipoprotein receptor superfamily. In the currents study, we investigate the molecular mechanisms by which transforming growth factor-β (TGF-β), a key molecule of ARDS pathogenesis, drives downregulation of megalin expression and function. TGF-β treatment led to shedding and regulated intramembrane proteolysis of megalin at the cell surface and to a subsequent increase in intracellular megalin COOH-terminal fragment abundance resulting in transcriptional downregulation of megalin. Activity of classical protein kinase C enzymes and γ-secretase was required for the TGF-β-induced megalin downregulation. Furthermore, TGF-β-induced shedding of megalin was mediated by matrix metalloproteinases (MMPs)-2, -9, and -14. Silencing of either of these MMPs stabilized megalin at the cell surface after TGF-β treatment and restored normal albumin transport. Moreover, a direct interaction of megalin with MMP-2 and -14 was demonstrated, suggesting that these MMPs may function as novel sheddases of megalin. Further understanding of these mechanisms may lead to novel therapeutic approaches for the treatment of ARDS.


[Clinical Outcome of Surgical Resection for Renal Cell Carcinoma with Inferior Vena Cava Tumor Thrombus].
We analyzed 45 patients who were diagnosed with renal cell carcinoma with inferior vena cava tumor thrombus (IVC) and underwent surgical resection at Nagasaki University Hospital during the 17 years from March 2003 to November 2020. The median overall survival (OS) was 68.5, 53.5, 45.7, and 20.4 months, respectively, according to the tumor thrombus level (Lv) of I, II, III and IV, with a median level of (P=0.025). In multivariate analysis, pathological sarcomatoid changes were associated with risk of tumor recurrence in the postoperative complete remission group, and IVC thrombus level above Lv III was associated with poor prognosis in the postoperative incomplete remission group. On postoperative systemic treatment for the postoperative recurrence group and the incomplete remission group, overall survival was significantly prolonged in cases using immune checkpoint inhibitors. The results of surgical treatment of renal cell carcinoma with IVC tumor embolization were analyzed. Patients who underwent surgical resection and achieved postoperative complete remission had a relatively long prognosis with a median OS of more than 6 years. In contrast, patients with metastases, especially those with postoperative incomplete remission group, had a poor prognosis despite surgical resection, depending on the patient's situation.


[Non-surgical therapy for ulcerative colitis].
Ulcerative colitis involving primarily the mucosa of the colon and rectum is a diffuse and nonspecific inflammatory disease. Immunocompetent cells infiltrating in the inflammed mucosa are mainly lymphocytes, macrophages and neutrophils. These activated cells produce proinflammatory cytokines such as IL-1, IL-6, IL-8 and TNF alpha and inflammatory activators such as PAF, leukotriene, prostaglandins, free radicals and proteases, resulting in acute on chronic states. Non-surgical therapy for ulcerative colitis includes basic medical therapy with sulfasulphapyridine, 5-ASA, corticosteroids and immune suppressive drugs as well as new therapies, which are leukocytapheresis, granulocytapheresis, anticytokine therapy with antiTNF alpha monoclonal antibody, IL-1ra and IL-10, intravenous treatment of massive immunoglobulins and transdermal nicotine therapy.


Systemic Preoperative Antibiotics with Mandible Fractures: Are They Indicated at the Time of Injury?
Mandible fractures are the most common result of facial trauma. The proximity of oral flora to the site of both the injury and resulting surgical instrumentation makes managing infection a unique challenge. The benefit of antibiotic prophylaxis at the time of surgical treatment of mandible fractures is well established. However, the routine use of antibiotics between the time of injury and surgery is of unclear benefit. We aim to define the role of antibiotics in the preoperative period: from the time of injury to surgical intervention. Demographic and clinical data were collected retrospectively on all patients who were treated for mandible fracture by the Division of Plastic and Reconstructive Surgery at our institution between 2003 and 2013. The use of both preoperative (between injury and surgery) and perioperative (at the time of surgery) systemic antibiotics was recorded along with the incidence of postoperative infections and other complications. Complete data were available for 269 patients. Of the 216 patients who received preoperative antibiotics, 22 (10%) developed an infection postoperatively. Of the 53 patients who did not receive preoperative antibiotics, 2 (4%) developed infection ( p = 0.184). Likewise, preoperative antibiotics were not significantly associated with hardware complication rates. In our retrospective review, the use of antibiotics between injury and surgical repair had no impact on postoperative infection rates. These data suggest that preoperative antibiotic use may actually be associated with an increased incidence of postoperative infection. Our results do not support the routine use of antibiotics between injury and surgical repair in patients with mandible fractures.


Indolacetic and humic acids induce lateral root development through a concerted plasmalemma and tonoplast H+ pumps activation.
Increasing evidences have indicated that humic substances can induce plant growth and productivity by functioning as an environmental source of auxinic activity. Here we comparatively evaluate the effects of indole-3-acetic acid (IAA) and humic acids (HA) isolated from two different soils (Inseptsol and Ultisol) and two different organic residues (vermicompost and sewage sludge) on root development and on activities of plasmalemma and tonoplast H(+ )pumps from maize roots. The data show that HA isolated from these different sources as well as low IAA concentrations (10(-10) and 10(-15) M) improve root growth through a markedly proliferation of lateral roots along with a differential activation not only of the plasmalemma but also of vacuolar H(+)-ATPases and H(+)-pyrophosphatase. Further, the vacuolar H(+)-ATPase had a peak of stimulation in a range from 10(-8) to 10(-10) M IAA, whereas the H(+)-pyrophosphatase was sensitive to a much broader range of IAA concentrations from 10(-3) to 10(-15) M. It is proposed a complementary view of the acid growth mechanism in which a concerted activation of the plasmalemma and tonoplast H(+ )pumps plays a key role in the root cell expansion process driven by environment-derived molecules endowed with auxinic activity, such as that of humic substances.


The mildest form of acute necrotizing encephalopathy associated with influenza A.
We experienced the mildest form of acute necrotizing encephalopathy associated with influenza A. A previously healthy 13-year-old girl had mildly decreased consciousness and delirious behavior lasting for a week. Diffusion-weighted imaging showed mildly high signal intensities in the bilateral thalami, deep white matter in the centrum semiovale, and frontal lobes. Conventional T (1)- or T (2)-weighted images revealed no abnormalities.


Evidence for a motor gamma-band network governing response interference.
The gamma-band response is thought to represent a key neural signature of information processing in the human brain. These brain signals have been associated with a variety of sensory modalities (vision, sensation, and audition) and also following basic motor responses, yet the functional significance of the motor gamma-band response remains unclear. We used the Multi-Source Interference Task (MSIT) to assess the sensitivity of these cortical motor gamma-band rhythms to stimuli producing response interference. We recorded MEG from adult participants (N=24) during MSIT task performance and compared motor gamma-band activity on Control and Interference trials. Reaction time on MSIT Interference trials was significantly longer (~0.2 s) for all subjects. Response interference produced a significant increase in motor gamma-band activity including ~0.5 s sustained increase in gamma-band activity from contralateral primary motor area directly preceding the response. In addition, activation of increased right Inferior Frontal Gyrus (R-IFG) was observed at gamma-band frequencies ~0.2 s prior to the button press response. Post-hoc analysis of R-IFG gamma-band activity was observed to correlate with reaction time increases to response interference. Our study is the first to record MEG during MSIT task performance. We observed novel activity of the motor gamma-band on interference trials which was sustained prior to the response and in novel locations including contralateral (BA6), and R-IFG. Our results support the idea that R-IFG is specialized structure for response control that also functions at gamma-band frequencies. Together, these data provide evidence for a motor gamma-band network for response selection and maintenance of planned behavior.


Crystallization and visible-near-infrared luminescence of Bi-doped gehlenite glass.
Gehlenite glass microspheres, doped with a different concentration of Bi3+ ions (0.5, 1, 3 mol%), were prepared by a combination of solid-state reaction followed by flame synthesis. The prepared glass microspheres were characterized from the point of view of surface morphology, phase composition, thermal and photoluminescence (PL) properties by optical and scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and PL spectroscopy. The closer inspection of glass microsphere surface by SEM confirmed a smooth surface. This was further verified by XRD. The basic thermal characteristics of prepared glasses, i.e. T g (glass transition temperature), T x (onset of crystallization peak temperature), T f (temperature of the inflection point of the crystallization peak) and T p (maximum of crystallization peak temperature), were estimated from the DSC records. High-temperature XRD experiments in the temperature interval range 600-1100°C were also performed. The PL emission properties of prepared glasses and their polycrystalline analogues (glass crystallized at 1000°C for 10 h) were studied in the visible and near-infrared (NIR) spectral range. When excited at 300 nm, the glasses, as well as their polycrystalline analogues, exhibit broad emission in the visible spectral range from 350 to 650 nm centred at about 410-450 nm, corresponding to Bi3+ luminescence centres. The emission intensity of polycrystalline samples was found to be at least 30 times higher than the emission of their glass analogues. In addition, a weak emission band was observed around 775 nm under 300 nm excitation. This band was attributed to the presence of a minor amount of Bi2+ species in prepared samples. In the NIR spectral range, the broad band emission was observed in the spectral range of 1200-1600 nm with the maxima at 1350 nm. The chemistry of Bi and its oxidation state equilibrium in glasses and polycrystalline matrices is discussed in detail.


Beyond prostate-specific antigen: new serologic biomarkers for improved diagnosis and management of prostate cancer.
The use of total prostate-specific antigen (tPSA) measurement has dramatically improved the ability to detect prostate cancer at earlier stages. However, as the number of men presenting with advanced disease (and high tPSA levels) has decreased, and given the fact that tPSA is highly reflective of benign prostatic hyperplasia, the need has emerged for novel biomarkers specifically associated with prostate cancer in order to improve predictive models. Several new biomarkers have shown promise, and studies continue to investigate the role of these markers in the detection, staging, and prognosis of prostate cancer. As new useful biomarkers continue to emerge, guidelines for their employment, as well as coordination of further research studies, are needed; a systematic, phased, nomogram-based model is a rational way to manage these efforts.


Patient Hand Colonization With MDROs Is Associated with Environmental Contamination in Post-Acute Care.
We assessed multidrug-resistant organism (MDRO) patient hand colonization in relation to the environment in post-acute care to determine risk factors for MDRO hand colonization. Patient hand colonization was significantly associated with environmental contamination. Risk factors for hand colonization included disability, urinary catheter, recent antibiotic use, and prolonged hospital stay. Infect Control Hosp Epidemiol 2017;38:1110-1113.


Prehospital Scheduling Management by the Critical Path Method for Burn Mass Casualty Incidents.
In 2015, a dust explosion occurred in New Taipei Water Park in Taiwan, and 499 casualties was appallingly high. In fact, the government spent 208 min of response time from receiving calls for emergency to sending the last wounded person to hospital. To stop a similar accident happening again, a well-prepared strategy, with an aim to reduce the rescue time, to respond to such an emergency is necessary. This study mainly focuses on the execution of mass casualty operations while both efficiency and quality of care are considered. We not only find that there is only 1 h or less to allocate rescue resources after a Burn Mass Casualty Incident (BMCI) happens but also shorten the response time. It is our first time to use a special method, called Critical Path Method (CPM), to analyze the rescue process. But before CPM is created, the benefit of available resources should be maximized, and timely, safe, and effective emergency medical services should be provided. With CPM, the interrelations of every activity can be visualized, and the most time-consuming activity can be found by this efficient time management. If the relationship between the predecessors and its successors operations of the most time-consuming activity item is reshaped, BMCI prehospital scheduling management becomes more effective based on its efficiency and quality of care.


Soporific Effect of Modified Suanzaoren Decoction and Its Effects on the Expression of CCK-8 and Orexin-A.
Suanzaoren decoction (SZRT), a classic Chinese herbal prescription, has been used as a treatment for insomnia for more than a thousand years. However, recent studies have found no significant effects of SZRT as a treatment for insomnia caused by gastric discomfort. Herein, we studied the effects of modified Suanzaoren decoction (MSZRD) on gastrointestinal disorder-related insomnia. The main constituents of MSZRD were spinosin (2.21 mg/g) and 6-feruloylspinosin (0.78 mg/g). A pentobarbital-induced animal model of insomnia showed that MSZRD shortened sleep latency and prolonged sleep time of the male Institute of Cancer Research (ICR) mice treated for 7 days with oral MSZRD. Sprague-Dawley male rats were treated daily with oral MSZRD or placebo for 11 days and then deprived of sleep for the last 4 days to establish a model of insomnia. Of note, MSZRD-treated animals had significantly improved body weight, organ index scores, and fecal moisture relative to placebo-treated animals, as well as reduced temperature. Sleep-deprived rats exhibited more exploratory behaviors in an open-field anxiety test; however, this effect was significantly reduced in MSZRD-treated animals. We found that MSZRD treatment decreased gastric acid pH, decreased the production of gastrin, pepsin, and Orexin-A, and increased the expression of MTL and CCK-8. Importantly, serum GABA concentration was increased by treatment with MSZRD, as reflected by a decreased Glu/GABA ratio. Treated animals had increased the expression of GAD1, GABARA1, and CCKBR but decreased the expression of Orexin R1. In summary, these results suggest that MSZRD has soporific and gastroprotective effects that may be mediated by differential expression of CCK-8 and Orexin-A.


Blast and penetrating fragment injuries to the extremities.
Blast injury to the extremities is the most common form of injury in recent military campaigns and in civilian terror attacks. Most orthopaedic trauma is caused by the secondary effect of blast--penetrating fragment injury. Timely wound débridement and excision of contaminated or avascular tissue, along with prevention of sepsis, are crucial to managing extremity injury. Late reconstruction and functional results are very challenging for the surgical team to achieve.


[First results of clinical diagnostic analysis of post-COVID peripheral neuropathy].
This analysis of ocular manifestations of the COVID-19 that can occur both in the acute and the post-COVID period focuses on pathological changes associated with hypercoagulation: thrombosis of the central retinal vein, occlusion of the central retinal artery, and decreased peripapillary perfusion. Potential changes in corneal nerve fibers (CNF) associated with coronavirus infection remain poorly understood. Meanwhile, previous studies have shown the possibility of using CNF as biomarkers of polyneuropathy (PNP). To study clinical and diagnostic features of post-COVID PNP. We examined 9 female patients aged 32 to 51 years who had suffered an infection caused by SARS-CoV-2 of varying severity. The patients were divided into two groups: the first consisted of 6 patients with clinical manifestations of PNP in the form of neuropathic pain, the second - 3 patients without clinical manifestations. Patients of group 1 underwent comprehensive examination including neurological examination, confocal microscopy of the cornea (in vivo CM), electroneuromyography (ENMG) of the nerves of the upper and lower extremities, quantitative sensory testing in the zone of painful sensations, while patients of group 2 only underwent in vivo CM. All patients of the first group, within 5-40 days after the onset of infection caused by SARS-CoV-2, exhibited symptoms of damage to various parts of the nervous system (peripheral nerves, thoracic spinal roots, trigeminal nerve). The main - and in most cases the only - symptom of the disease was neuropathic pain syndrome. In Guillain-Barré syndrome, for the first time using in vivo CM, the following changes were revealed: enlargement of in Langerhans cells, shortening of CNF and their processes, presence of neuromas. The standard neurological examination of patients with post-COVID neuropathy should be supplemented with special diagnostic methods for assessment of structural and functional state of the peripheral nerves. The in vivo CM method is capable of non-invasive assessment of changes in thin CNF and, with accumulation of empirical data, can be included in the algorithm for diagnosing post-COVID PNP.


Self-Assembled Reduced Albumin and Glycol Chitosan Nanoparticles for Paclitaxel Delivery.
Cancer continues to pose health problems for people all over the world. Nanoparticles (NPs) have emerged as a promising platform for effective cancer chemotherapy. NPs formed by the assembly of proteins and chitosan (CH) through noncovalent interactions are attracting a great deal of interest. However, the poor water solubility of CH and low stability of this kind of NP limit its practical application. Herein, the formation of reduced bovine serum albumin (rBSA) and glycol chitosan (GC) nanoparticles (rBG-NPs) stabilized by hydrophobic interactions and disulfide bonds was demonstrated for paclitaxel (PTX) delivery. The effects of the rBSA:GC mass ratio and pH on the particle size, polydispersity index (PDI), number of particles, and surface charge were evaluated. The formation mechanism and stability of the NPs were determined by compositional analysis and dynamic light scattering. Hydrophobic and electrostatic interactions were the driving forces for the formation of the rBG-NPs, and the NPs were stable under physiological conditions. PTX was successfully encapsulated into rBG-NPs with a high encapsulation efficiency (∼90%). PTX-loaded rBG-NPs had a particle size of ∼400 nm with a low PDI (0.2) and positive charge. rBG-NPs could be internalized by HeLa cells, possibly via endocytosis. An in vitro cytotoxicity study revealed that PTX-loaded rBG-NPs had anticancer activity that was lower than that of a Taxol-like formulation at 24 h but had similar activity at 48 h, possibly because of the slow release of PTX into the cells. Our study suggests that rBG-NPs could be used as a potential nanocarrier for hydrophobic drugs.