The Krüppel-Like Factors and Control of Energy Homeostasis.
Nutrient handling by higher organisms is a complex process that is regulated at the transcriptional level. Studies over the past 15 years have highlighted the critical importance of a family of transcriptional regulators termed the Krüppel-like factors (KLFs) in metabolism. Within an organ, distinct KLFs direct networks of metabolic gene targets to achieve specialized functions. This regulation is often orchestrated in concert with recruitment of tissue-specific transcriptional regulators, particularly members of the nuclear receptor family. Upon nutrient entry into the intestine, gut, and liver, KLFs control a range of functions from bile synthesis to intestinal stem cell maintenance to effect nutrient acquisition. Subsequently, coordinated KLF activity across multiple organs distributes nutrients to sites of storage or liberates them for use in response to changes in nutrient status. Finally, in energy-consuming organs like cardiac and skeletal muscle, KLFs tune local metabolic programs to precisely match substrate uptake, flux, and use, particularly via mitochondrial function, with energetic demand; this is achieved in part via circulating mediators, including glucocorticoids and insulin. Here, we summarize current understanding of KLFs in regulation of nutrient absorption, interorgan circulation, and tissue-specific use.


Identification and mapping of H32, a new wheat gene conferring resistance to Hessian fly.
H32 is a newly identified gene that confers resistance to the highly pervasive Biotype L of the Hessian fly [ Mayetiola destructor (Say)]. The gene was identified in a synthetic amphihexaploid wheat, W-7984, that was constructed from the durum 'Altar 84' and Aegilops tauschii. This synthetic wheat is one of the parents of the marker-rich ITMI population, which consists of 150 recombinant inbred lines (RILs) derived by single-seed descent from a cross with 'Opata 85'. Linkage analysis of the H32 locus in the ITMI population placed the gene between flanking microsatellite (SSR) markers, Xgwm3 and Xcfd223, at distances of 3.7 and 1.7 cM, respectively, on the long arm of chromosome 3D. The Xgwm3 primers amplified codominant SSR alleles, a 72 bp fragment linked in coupling to the resistance allele and an 84 bp fragment linked in repulsion. Primers for the SSR Xcfd223 amplified a 153 bp fragment from the resistant Synthetic parent and a 183 bp fragment from the susceptible Opata line. Deletion mapping of the flanking Xgwm3 and Xcfd223 markers located them within the 3DL-3 deletion on the distal 19% of the long arm of chromosome 3D. This location is at least 20 cM proximal to the reported 3DL location of H24, a gene that confers resistance to Biotype D of the Hessian fly. Tight linkage of the markers will provide a means of detecting H32 presence in marker-assisted selection and gene pyramiding as an effective strategy for extending durability of deployed resistance.


Analysis of lung surfactant in the metamorphosing bullfrog (Rana catesbeiana).
In bullfrog (Rana catesbeiana) tadpoles, the lung begins to function at an advanced stage of metamorphosis. As a preliminary step for investigation of the mechanisms involved in lung maturation, pulmonary surfactant was prepared from tadpoles at advanced stages of metamorphosis and its biochemical properties were analyzed. Surfactant phospholipid analysis revealed that the major constituent was phosphatidylcholine (PC), as examined in the animals at late climax (stage 24). Other detectable phospholipids were phosphatidylethanolamine, phosphatidylserine, sphingomyelin, and phosphatidylglycerol, a marker lipid in mammalian surfactant. As in mammals, PC in the surfactant was rich in saturated fatty acids, about 50% of fatty acid moieties being palmitic acid. The content of surfactant PC in the lung increased moderately around mid-climax and markedly at the end of climax. The effect of antiserum against bullfrog prolactin (PRL) on the pulmonary surfactant was studied in climactic tadpoles. The content of surfactant PC in the lung of the antiserum-treated larvae was lower than that in the lung of the normal rabbit serum-injected larvae, whereas the content of PC in the whole lung did not differ between the antiserum-treated and control groups. The results suggest that synthesis of surfactant in the amphibian lung is enhanced as metamorphosis progresses and that PRL is involved in lung maturation.


Understanding bovine trypanosomiasis and trypanotolerance: the promise of functional genomics.
African bovine trypanosomiasis, caused by the protozoan parasite Trypanosoma congolense, is endemic throughout sub-Saharan Africa and is a major constraint on livestock production. A promising approach to disease control is to understand and exploit naturally evolved trypanotolerance. We describe the first attempt to investigate the transcriptional response of susceptible Boran (Bos indicus) cattle to trypanosome infection via a functional genomics approach using a bovine total leukocyte (BOTL) cDNA microarray platform. Four male Boran cattle were experimentally infected with T. congolense and peripheral blood mononuclear cells (PBMC) were collected before infection and 13, 17, 23 and 30 days post-infection (dpi). A reference experimental design was employed using a universal bovine reference RNA pool. Data were normalised to the median of a set of invariant genes (GAPDH) and BRB-Array tools was used to search for statistically significant differentially expressed genes between each time-point. Using a set of 20 microarray hybridisations, we have made a significant contribution to understand the temporal transcriptional response of bovine PBMC in vivo to a controlled trypanosome infection. The greatest changes were evident 13 dpi after parasites were first detected in the blood. Significant differences were observed in clusters of protein kinase C subunits and MHC class I/II related molecules.


COVID-19-Associated Ischemic Colitis: A Rare Manifestation of COVID-19 Infection-Case Report and Review.
Following the first report of COVID-19 infection in December 2019 as a respiratory illness, it has proven to be a multisystem disease. There are few reported cases of ischemic colitis with COVID-19 infection in the medical literature to date and we have limited understanding of its pathophysiology. We report 2 cases of ischemic colitis as the only manifestation of COVID-19. In addition, we review the current limited literature regarding COVID-19-associated ischemic colitis.


Liquid Metal-Based Soft Electronics for Wearable Healthcare.
Wearable healthcare devices have garnered substantial interest for the realization of personal health management by monitoring the physiological parameters of individuals. Attaining the integrity between the devices and the biological interfaces is one of the greatest challenges to achieving high-quality body information in dynamic conditions. Liquid metals, which exist in the liquid phase at room temperatures, are advanced intensively as conductors for deformable devices because of their excellent stretchability and self-healing ability. The unique surface chemistry of liquid metals allows the development of various sensors and devices in wearable form. Also, the biocompatibility of liquid metals, which is verified through numerous biomedical applications, holds immense potential in uses on the surface and inside of a living body. Here, the recent progress of liquid metal-based wearable electronic devices for healthcare with respect to the featured properties and the processing technologies is discussed. Representative examples of applications such as biosensors, neural interfaces, and a soft interconnection for devices are reviewed. The current challenges and prospects for further development are also discussed, and the future directions of advances in the latest research are explored.


Surface modification of biomaterials: a quest for blood compatibility.
Cardiovascular implants must resist thrombosis and intimal hyperplasia to maintain patency. These implants when in contact with blood face a challenge to oppose the natural coagulation process that becomes activated. Surface protein adsorption and their relevant 3D confirmation greatly determine the degree of blood compatibility. A great deal of research efforts are attributed towards realising such a surface, which comprise of a range of methods on surface modification. Surface modification methods can be broadly categorized as physicochemical modifications and biological modifications. These modifications aim to modulate platelet responses directly through modulation of thrombogenic proteins or by inducing antithrombogenic biomolecules that can be biofunctionalised onto surfaces or through inducing an active endothelium. Nanotechnology is recognising a great role in such surface modification of cardiovascular implants through biofunctionalisation of polymers and peptides in nanocomposites and through nanofabrication of polymers which will pave the way for finding a closer blood match through haemostasis when developing cardiovascular implants with a greater degree of patency.


Hypogonadism and hormone replacement therapy on bone mass of adult women with thalassemia major.
We studied bone mass and metabolism in 30 adult women (age 28.5 +/- 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 +/- 0.31; femoral neck -0.60+/-0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine -2.35 +/- 0.2, femoral neck -1.83 +/- 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 +/- 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual.


Pharmacokinetic profile of a new diclofenac prodrug without gastroulcerogenic effect.
Gastrotoxicity is a major problem for long-term therapy with non-steroidal anti-inflammatory drugs (NSAIDs). DICCIC (1-(2,6-dichlorophenyl)indolin-2-one) is a new diclofenac prodrug, which has proven anti-inflammatory activity without gastroulcerogenic effect. The aim of this work was to compare the pharmacokinetic profiles of diclofenac from DICCIC (7.6 mg/kg equivalent to 8.1 mg/kg diclofenac) and diclofenac (8.1 mg/kg) administration in Wistar rats weighing 250-300 g (n=20). The doses were calculated by interspecific allometric scaling based on the 2 mg/kg from diary human dose of diclofenac. Blood samples were collected in heparinized tubes via the femoral artery through the implanted catheter. The plasma was separated and quantitation was made in a HPLC system with a UV-Vis detector. The confidence limits of the bioanalytical method were appropriate for its application in a preclinical pharmacokinetic study. The AUC of diclofenac from DICCIC (53.7± 5.8 ug/mL.min) was significantly less (Mann Whitney test, p<0.05) than that of diclofenac from diclofenac administration (885.9 ± 124,8 ug/mL.min). Terminal half-life of diclofenac from DICCIC (50.1 ± 17.2 min) was significantly less (Mann Whitney test, p<0.05) than that of diclofenac from diclofenac administration (247.4 ± 100.9 min). Still the parameters clearance and distribution volume were calculated for diclofenac from diclofenac, whose results were 9.2 ±1.2 mL/min.kg and 3.3 ±1.2 L/kg, respectively. The results of DICCIC from DICCIC administration were 108.9 ± 19.6 mL/min.kg and 7.8 ± 2.4 L/kg for clearance and distribution volume, respectively. The pharmacokinetic profile demonstrated that there was an increase in diclofenac elimination and a lower exposure to diclofenac with administration of DICCIC compared to diclofenac.


Tumor characteristics and surgical outcomes of intracranial subependymomas: a systematic review and meta-analysis.
The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies. A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted. Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39-7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03-7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78-2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35-1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27-2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%). Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.


Effects of taclamine (AY-22,214), a new psychoactive agent, on catecholamine and serotonin metabolism.
The effects of a new psychopharmacologically-active agent taclamine (AY-22,214 (AY)(a dibenzocycloheptaisoquinolines)) on noradrenaline (NA), dopamine (DA) and serotonin(5-HT) turnover in the brains of normal and/or stressed animals were determined by the use of both non-isotopic and isotopic techniques; a comparison with chlordiazepoxide (CL) was carried out. Both AY and CL antagonized the increase in NA and 3H-NA turnover due to immobilization stress in whole, and selected regions, of the rat brain. AY, unlike CL did not decrease 3H-NA turnover in brains of non-stressed animals. AY accelerated the turnover of DA in whole brain and 3H-DA in the striatum. In contrast, CL decreased turnover of each. AY did not alter 5-HT turnover. CL decreased 14C-5-HT turnover in regions of rat brain; in addition, it antagonized the pargyline-induced rise in 5-HT and potentiated the subsequent fall in levels of 5-HIAA. Neither AY nor CL affected the 5-HT uptake in the mouse brain. It is concluded that AY appears to exhibit both similarities and differences to CL with regard to its effects on biogenic amine turnover.


Antoni marian gabryszewski as a pioneer of orthopaedics and rehabilitation in poland.
This article describes the work of Dr. Antoni Marian Gabryszewski, orthopaedic surgeon, associate professor at Lvov University, towards the development of orthopaedics and rehabilitation in Poland before World War I. It is based on archival materials, publications in medical journals and articles from the daily press of that time. The author presents little-known facts concerning Dr. Gabryszewski's occupational and academic activity and his work at the Surgery Dept. of Lvov University as well as his habilitation dissertation, regarded as the first attempt to position orthopaedics as distinct from surgery in Poland. The article also describes his long-term work at the private Orthopaedic Facility established in 1898 in Lvov which later incorporated the Zander Institute in 1908. The Zander Institute was the first in Galicia to offer exercise machines designed by Dr. Gustav Zander, imported from Stockholm and enjoying an extraordinary popularity in the world. Dr. Gabryszewski's practice as a spa doctor, which he pursued in Iwonicz Zdrój in the summer months, is also presented. Dr. A. Gabryszewski introduced comprehensive rehabilitation to the treatment of orthopaedic patients both at the Surgery Dept. of Lvov University and at his Orthopaedic Facility. He used therapeutic gymnastics (particularly mechanotherapy), therapeutic massage, physical therapy and orthopaedic aids. Analysis of the source materials leads to unequivocal conclusions attesting to Dr. A. Gabryszewski's pioneering role and significant contribution to the development of orthopaedics and rehabilitation in Poland.


Assessing computational methods of cis-regulatory module prediction.
Computational methods attempting to identify instances of cis-regulatory modules (CRMs) in the genome face a challenging problem of searching for potentially interacting transcription factor binding sites while knowledge of the specific interactions involved remains limited. Without a comprehensive comparison of their performance, the reliability and accuracy of these tools remains unclear. Faced with a large number of different tools that address this problem, we summarized and categorized them based on search strategy and input data requirements. Twelve representative methods were chosen and applied to predict CRMs from the Drosophila CRM database REDfly, and across the human ENCODE regions. Our results show that the optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. We analyze the principal features that distinguish the methods that performed well, identify weaknesses leading to poor performance, and provide a guide for users. We also propose key considerations for the development and evaluation of future CRM-prediction methods.


IL-33 mediates multi-walled carbon nanotube (MWCNT)-induced airway hyper-reactivity via the mobilization of innate helper cells in the lung.
Allergic asthma is a chronic inflammatory disorder of the airway associated with bronchial obstruction, airway hyper-reactivity (AHR), and mucus production. The epithelium may direct and propagate asthmatic-like responses. Central to this theory is the observation that viruses, air pollution, and allergens promote epithelial damage and trigger the generation of IL-25, IL-33, and TSLP via innate pathways such as TLRs and purinergic receptors. Similarly, engineered nanomaterials promote a Th2-associated pathophysiology. In this study, we tested the hypothesis that instillation of multi-walled carbon nanotubes (MWCNT) impair pulmonary function in C57Bl/6 mice due to the development of IL-33-dependent Th2-associated inflammation. MWCNT exposure resulted in elevated levels of IL-33 in the lavage fluid (likely originating from airway epithelial cells), enhanced AHR, eosinophil recruitment, and production of Th2-associated cytokines and chemokines. Moreover, these events were dependent on IL-13 signaling and the IL-33/ST2 axis, but independent of T and B cells. Finally, MWCNT exposure resulted in the recruitment of innate lymphoid cells. Collectively, our data suggest that MWCNT induce epithelial damage that results in release of IL-33, which in turn promotes innate lymphoid cell recruitment and the development of IL-13-dependent inflammatory response.


Secondary infertility and retained fetal bone fragments.
Retained fetal bone fragments may be an underreported and underappreciated cause of secondary infertility among women with an antecedent spontaneous or induced abortion. Three patients with a history of an antecedent induced abortion presented with secondary infertility. The infertility evaluation diagnosed retained intrauterine fetal bone fragments. After removal of the bone fragments, two of the three patients successfully conceived. Secondary infertility may be the only presenting symptom for women with retained fetal bone fragments. Women with secondary infertility and antecedent spontaneous or induced abortion may benefit from uterine evaluation with ultrasonography before initiating infertility treatment. For patients with findings of focal echogenic shadowing lesions at ultrasonography, we recommend ultrasonography-guided hysteroscopy to ensure that bone fragments embedded within the myometrium are not missed and are completely resected.


Chronological changes in rhinitis symptoms present in school-aged children with allergic sensitization.
It is difficult to accurately predict the natural course of allergic rhinitis (AR), because it is affected by a wide variety of environmental influences, as well as genetic predisposition. Considering the high prevalence of allergic rhinitis in children and adolescents, caregivers should be given appropriate information regarding the disease course. This study aimed to understand the prognosis of allergic rhinitis by examining the relationship between allergic sensitization and rhinitis symptoms during this developmental period. This cross-sectional study included 1069 children aged 9-16 years from the Korean International Study of Asthma and Allergies in Childhood Survey database who had completed health questionnaires, and for whom skin prick test results were available. Data were collected during May 2016. The distribution of sensitization and allergic symptoms was compared by age groups (elementary, middle, and high school). Data were analyzed using linear-by-linear analysis. Sensitization to at least one tested allergen differed by age (59.2%, 58.3%, 68.2%, in elementary, middle, and high school students, respectively; p = 0.025), and seasonal allergen sensitization (35.0%, 37.1%, 53.9%, respectively) increased with age (p < 0.001). Conversely, the proportion of rhinitis symptoms among sensitized children decreased as age increased (58.80%, 52.90%, 49.70%, respectively; p = 0.047). However, the rate of non-allergic rhinitis was age-independent. With increasing age during childhood and adolescence, symptomatic allergic rhinitis decreases; thus, subclinical allergic rhinitis increases. This suggests that the symptoms of later-sensitized children are less clearly manifested, or that the symptoms reduce as previously sensitized children mature. This should be clarified further in a longitudinal study.


Amino acid residues essential for biological activity of a peptide derived from a major histocompatibility complex class I antigen.
The stimulatory activity of peptides from the alpha 1 domain of the major histocompatibility complex (MHC) class I antigen on adipose cell glucose transport was previously shown to require a preformed, ordered conformation of the peptide. The two peptides studied previously were Dk-(61-85) (ERETQIAKGNEQSFRVDLRTLLRYY) and Dk-(69-85). We now show that systematic alanine substitution in Dk-(69-85) identifies residues that are essential for biological activity. Ordered structure of the peptides, estimated by circular dichroism, was found in all peptides with activity, but with a complex variety of spectra. Inactive peptides were in either a random coil or an ordered structure. Ordered structure, therefore, is not sufficient for activity. The peptides self-interact in the absence of cells and form aggregates that precipitate upon centrifugation. The tendency to aggregate is correlated with biological potency. Only MHC class I molecules have significant homology to the peptides studied here. The peptide self-interaction suggests that the biological effects in cells, which result from inhibition of receptor and transporter internalization, may be due to the binding (tantamount to self-interaction) of the peptide to the homologous sequences in the alpha 1 domain of the MHC class I molecule.


Dynamics of biochemical properties associated with soil nitrogen mineralization following nitrification inhibitor and fungicide applications.
Agrochemical applications may have side effects on soil biochemical properties related to soil nitrogen (N) mineralization and thus affect N cycling. The present study aimed to evaluate the effects of nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) and fungicide iprodione on soil neutral protease (NPR), alkaline protease (APR), chitinase (CHI), and their functional genes (nprA, aprA, and chiA) related to soil N mineralization. The following four treatments were included: blank control (CK), single DMPP application (DAA), weekly iprodione applications (IPR), and the combined applications of DMPP and iprodione (DI). Compared with the CK treatment, DMPP application significantly inhibited the CHI activity in the first 14 days of incubation, and iprodione applications, particularly when applied alone, decreased the NPR, APR, and CHI activities. Relative to the IPR treatment, extra DMPP application had the potential to alleviate the inhibitory effects of iprodione on the activities of these enzymes. DMPP application significantly increased aprA gene abundances after 14 days of incubation. However, repeated iprodione applications, alone or with the DMPP, decreased nprA and chiA gene abundances. Relative to the CK treatment, DMPP application generated negligible effects on the positive/negative correlations between soil enzyme activities and the corresponding functional gene abundances. However, the positive correlation between the CHI activity and chiA gene abundance was changed to negative correlation by repeated iprodione applications, alone or together with the DMPP. Our results demonstrated that agrochemical applications, particularly repeated fungicide applications, can have inadvertent effects on enzyme activities and functional gene abundances associated with soil N mineralization.


Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid.
A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance.


Comparison between Malerba osteotomy and combined Evans/medial displacement calcaneal osteotomies for the management of flexible pes planus in young adults: a prospective randomised control trial, three years follow-up.
The aim of the current study is to evaluate the functional and radiological outcomes of Malerba osteotomy in comparison to the standardized combined Evans/Medial Displacement Calcaneal Osteotomy (MDCO) in the management of symptomatic flexible pes planus in young adults. Prospective randomized control trial included 34 feet (33 patients), 17 cases in each group. Functionally, patients were assessed by AOFAS and FADI scores. Radiographic evaluation included calcaneal pitch, lateral talo-1st metatarsal, AP talo-first metatarsal, AP talo-calcaneal angles, and the talar coverage percentage. Pre-operative and three years follow-up scores and angles were compared between both groups. No statistically significant difference could be detected between both groups (P value 0.87). However, the data showed statistically significant difference in each group when comparing (pre-operative and third year follow-up scores and angles) (P value < 0.001). The mean union rate was eight weeks in Malerba group and nine weeks in Evans/MDCO group. No incidence of nonunion. Complications like calcaneocuboid subluxation, calcaneal anterior process fracture, and lateral column pain were exclusively reported in Evans/MDCO group. Malerba osteotomy is a strong valid option for the operative management of flexible pes planus in young adults. Authors recommend Malerba osteotomy in all mild and moderate deformities due to lower complication rate while the combined Evans/MDCO is preferred in severe deformity due to relatively higher corrective power with consideration of possible complications.


Spectroscopic signatures of halogens in clathrate hydrate cages. 1. Bromine.
We report the first UV-vis spectroscopic study of bromine molecules confined in clathrate hydrate cages. Bromine in its natural hydrate occupies 51262 and 51263 lattice cavities. Bromine also can be encapsulated into the larger 51264 cages of a type II hydrate formed mainly from tetrahydrofuran or dichloromethane and water. The visible spectra of the enclathrated halogen molecule retain the spectral envelope of the gas-phase spectra while shifting to the blue. In contrast, spectra of bromine in liquid water or amorphous ice are broadened and significantly more blue-shifted. The absorption bands shift by about 360 cm-1 for bromine in large 51264 cages of type II clathrate, by about 900 cm-1 for bromine in a combination of 51262 and 51263 cages of pure bromine hydrate, and by more than 1700 cm-1 for bromine in liquid water or amorphous ice. The dramatic shift and broadening in water and ice is due to the strong interaction of the water lone-pair orbitals with the halogen sigma* orbital. In the clathrate hydrates, the oxygen lone-pair orbitals are all involved in the hydrogen-bonded water lattice and are thus unavailable to interact with the halogen guest molecule. The blue shifts observed in the clathrate hydrate cages are related to the spatial constraints on the halogen excited states by the cage walls.


Re: Sheng W, Zhang H, Kirschner-Hermanns R. Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis. Neurourol Urodyn. 2017;9999:1-8. doi: 10.1002/nau.23210.
Sheng et al (Neurourology and Urodynamics 2017; DOI: 10.1002/nau.23210) presented a meta-analysis based on 17 publications to show that urinary nerve growth factor (NGF) may be a useful biomarker for overactive bladder syndrome (OAB). Unfortunately, 13 of the 17 studies used an unspecifc enzyme-linked immunosorbent assay (ELISA), the Promega NGF Emax Immunoassay, to quantify NGF in urine. This assay did not detect NGF in urine, but other urinary components, such as immunoglobulin G, and in 2014, it was withdrawn from the market. With other NGF-ELISAs, urinary NGF concentrations were found to be below detection level for both, OAB and healthy controls. Currently, ELISA techniques are not sensitive enough to detect NGF in urine, and urinary NGF cannot be used as a biomarker for OAB.


[Personality profile of patients with anxiety disorder, as studied with the 16PF Cattell's questionnaire and Cloninger's TCI].
The aim of the present study is a characterisation of the personality dimensions of patients with anxiety disorder. Personality of 103 patients with different mixed ICD-10 diagnosis of anxiety disorders (79 females, 24 males, mean age: 38 +/- 12 years) were studied and compared to 183 healthy controls (117 females, 66 males, mean age: 35 +/- 14) using the 16 PF Cattell's Questionnaire and Cloninger's TCI. Spielberger's State and Trait Anxiety Inventory and Self-evaluation of the Beck's Depression Scale were also applies. Levels of anxiety and depression were significantly higher in patients. It was found that patients with anxiety disorders scored higher in Cattell's following factors: O, Q4 and lower in: C, E, F, H, Q3 when compared to standard population norms. Following TCI scales differentiated the personality of patients when compared to the controls: A significant increase of all HA subscales, decrease of NS in females and NS1 in both female and male patients, increase in RD1 and decrease in RD3 in patients, decrease of P, SD, C (except C4 and C5 subscales) were observed. Both TCI and 16 PF describe similar traits in the personality of patients with anxiety disorders, and are helpful in the diagnosis and prognosis of therapy.


The SHAZ! project: results from a pilot randomized trial of a structural intervention to prevent HIV among adolescent women in Zimbabwe.
Adolescent females in Zimbabwe are at high risk for HIV acquisition. Shaping the Health of Adolescents in Zimbabwe (SHAZ!) was a randomized controlled trial of a combined intervention package including life-skills and health education, vocational training, micro-grants and social supports compared to life-skills and health education alone. SHAZ! was originally envisioned as a larger effectiveness trial, however, the intervention was scaled back due to contextual and economic conditions in the country at the time. SHAZ! enrolled 315 participants randomly assigned to study arm within blocks of 50 participants (158 intervention and 157 control). The intervention arm participants showed statistically significant differences from the control arm participants for several outcomes during the two years of follow up including; reduced food insecurity [IOR = 0.83 vs. COR = 0.68, p-0.02], and having their own income [IOR = 2.05 vs. COR = 1.67, p = 0.02]. Additionally, within the Intervention arm there was a lower risk of transactional sex [IOR = 0.64, 95% CI (0.50, 0.83)], and a higher likelihood of using a condom with their current partner [IOR = 1.79, 95% CI (1.23, 2.62)] over time compared to baseline. There was also evidence of fewer unintended pregnancies among intervention participants [HR = 0.61, 95% CI (0.37, 1.01)], although this relationship achieved only marginal statistical significance. Several important challenges in this study included the coordination with vocational training programs, the political and economic instability of the area at the time of the study, and the difficulty in creating a true standard of care control arm. Overall the results of the SHAZ! study suggest important potential for HIV prevention intervention packages that include vocational training and micro-grants, and lessons for further economic livelihoods interventions with adolescent females. Further work is needed to refine the intervention model, and test the impact of the intervention at scale on biological outcomes. ClinicalTrials.gov NCT02034214.


Meningioma accompanied by a subdural hematoma. A case report. Review of 17 cases in the literature.
Hemorrhage occurs extremely rare in meningioma. We have found only 17 cases of meningioma associated with subdural hematoma in the reviewed literature. We report a similar case of a 26-year-old woman who complained initially of paralysis of her left arm evolving into loss of consciousness accompanied by a spasm of the extremities and foam in the mouth. In the days immediately preceding admission into hospital she complained of headache, unsteadiness in walking and vomiting. On admission she was bradypsychic, time-disoriented and drowsy. Latent left-sided hemiparesis was established. A right carotid angiography gave indication of a subdural hematoma. The patient was operated on in an emergency. After evacuation of the hematoma a smooth tumour was found embedded in the brain with a cyst in it. The tumour was the size of an egg, soft and elastic. There were several bleeding vessels underneath. During operation the tumour was not in contact with dura mater. The histologic diagnosis was fibroblastic meningioma. After treatment the patient was discharged in good condition with slight hemiparesis.


Dynamics of temporal immune responses in nonhuman primates and humans immunized with COVID-19 vaccines.
We assessed the humoral immune responses to a COVID-19 vaccine in a well-controlled rhesus macaque model compared to humans immunized with two mRNA vaccines over several months post-second dose. The plasma IgG levels against seven coronaviruses (including SARS-CoV-2) and antibody subtypes (IgG 1-4 and IgM) against SARS-CoV-2 were evaluated using multiplex assays. The neutralization capacity of plasma antibodies against the original SAR-CoV-2 isolate and nine variants was evaluated in vaccinated humans and non-human primates. Immunization of macaques and humans with SARS-CoV-2 vaccines induced a robust neutralizing antibody response. In non-SIV-infected adult macaques immunized with an adenoviral vector expressing S-RBD (n = 7) or N protein (n = 3), elevated levels of IgG and neutralizing antibodies were detected 2 weeks post-second dose. Immune responses to the S-RBD vaccine in SIV-infected adult macaques (n = 2) were similar to the non-SIV-infected animals. Adult humans immunized with Pfizer (n = 35) or Moderna (n = 18) vaccines developed IgG and neutralizing antibodies at 4 weeks post-second dose. In both vaccine groups, IgG 1 was the predominant subtype, followed by IgG 3. The IgG levels, including total and IgG 1,2,3 elicited by the Moderna vaccine, were significantly higher than the corresponding levels elicited by the Pfizer vaccine at 4 weeks post-second dose. A significant correlation was observed between the plasma total IgG antibody levels and neutralization titers in both macaques and humans. Furthermore, broad-spectrum neutralization antibodies against several variants of SARS-CoV-2 were detected in the plasma of both macaques and humans after two vaccinations.


A Syrian man with abdominal pain.
A 32-year-old man presented with progressive abdominal pain, nausea and vomiting after swallowing a packet of dollar bills, his entire money savings, during his journey to Europe as a refugee. Subsequent imaging confirmed the presence of a foreign body in his stomach, which required surgical intervention to be removed. This is one of many cases that illustrate the hopeless circumstances people in the Middle-Eastern warzone are currently facing.


[Fundamental and clinical studies on sisomicin in children (author's transl)].
Fundamental and clinical studies on sisomicin, a new aminoglycoside antibiotic were carried out and the following results were obtained. 1. Antibacterial activity of sisomicin was superior to that of gentamicin, amikacin, cefazolin and ampicillin against S. aureus and Ps. aeruginosa. Against E. coli and K. pneumoniae, it was superior to that of amikacin, cefazolin, ampicillin and equal or slightly superior to that of gentamicin. 2. Mean serum levels of sisomicin were 18.0 +/- 0.5 microgram/ml, 15.7 +/- 1.3 microgram/ml, 9.6 +/- 0.6 microgram/ml, 3.2 +/- 0.4 microgram/ml, 1.7 +/- 0.2 microgram/ml and 0.95 microgram/ml at 1/2, 1, 2, 4, 6 and 8 hours after a single intramuscular administration of sisomicin 2.0 mg/kg to 3 children. Mean half-life time was 1.6 +/- 0.2 hours. Mean urinary recovery was 60.4 +/- 7.5% within 6 hours after administration of sisomicin 1.6-2.1 mg/kg to 4 children. 3. Sisomicin was given intramuscularly to 13 children with acute pyelitis (11), acute cystitis (1) and stomatitis gangrenosa and cervical lymphadenitis (1). The daily dose was 2.0 -4.2 mg/kg, divided into twice. Clinical response was excellent in 8 and good in 5. In bacteriological examinations, 13 pathogens (E. coli 9, K. pneumoniae 2, Ps. aeruginosa 2) were eradicated after administration. No adverse reactions were observed.


Carbofuran induced impairment in the hypothalamo-neurohypophyseal-gonadal complex in the teleost, Channa punctalus (Bloch).
The effect of chronic exposure to carbofuran (4.5 ppm in static water) for six months on the gonadal histophysiology and hypothalamo-neurohypophyseal complex was studied in Channa punctatus. Experimental observations revealed significant inhibition of gonadal development with associated degenerative abnormalities as evidenced by ovarian and testicular histology and reduced gonadosomatic index. Degenerative changes in ovary were exihibited by stage I (oogonium) and stage II (immature/non-vitellogenic) oocytes as marked by perinuclear ooplasmic lysis, clumping and dissolution resulting in disintigration of nuclear material altogether attributed to complete degeneration of such oocytes. Testicular deleterious changes included degeneration of spermatogenic elements and necrosis of interstitial cells of Leydig. Correlative histophysiological changes were also observed in the pituitary gonadotrophs and hypothalamic, nucleus pre-opticus, neurons that were smaller, inactive and less in number with associated necrosis. Corresponding to the changes in nucleus pre-opticus neurons, significant inhibition of brain monoamine oxidase enzyme activity was also recorded in treated group. These observations suggest that carbofuran even at low concentration level under long-term exposure is capable of inducing retardation of gonadal development which might have been mediated through the impairment of the hypothalamo-neurohypophyseal-gonadal axis in this species.


The change experience: how we updated our perioperative nursing documentation.
This article aims to describe the review and modification process of the perioperative nursing documentation forms within a large urban theatre complex. It is hoped that by making this process more transparent other perioperative practitioners will be encouraged to review and update the documentation used within their departments.


Evaluation and comparison of efficacy of three desensitizing dentifrices on dentinal hypersensitivity and salivary biochemical characteristics: A randomized controlled trial.
This study aimed to evaluate and compare the efficacy of three desensitizing dentifrices on dentinal hypersensitivity (DH) and salivary biochemical characteristics. A randomized, parallel arm, triple-blinded, clinical trial was conducted over a period of 12 weeks, with a total of three visits: baseline, 6 weeks, and 12 weeks. Calcium sodium phosphosilicate, potassium nitrate and amine fluoride dentifrices were compared. A total of 68 subjects who satisfied the inclusion criteria were included and randomly divided into four groups. Visual analog scale scores for controlled air stimulus were used to assess dentinal sensitivity and salivary pH and buffering capacity were recorded at baseline, 6 and 12 weeks. All groups showed a reduction in sensitivity scores at 6 and 12 weeks. The calcium sodium phosphosilicate group showed a higher degree of effectiveness in reducing DH than potassium nitrate, amine fluoride dentifrices, and placebo for sensitivity measures. Salivary pH of calcium sodium phosphosilicate group was more toward neutral, and the buffering capacity of the same group showed significant changes from baseline to 6 and 12 weeks compared to the other groups. The desensitizing toothpaste containing calcium sodium phosphosilicate was found to be more effective in reducing DH and showed improvement in salivary biochemical characteristics over a period of 12 weeks compared to others.


Microvascular Fragment Transplantation Improves Rat Dorsal Skin Flap Survival.
The development of flap necrosis distally remains a concern during microsurgical flap transfers because, at least in part, of decreased perfusion. Microvascular fragments (MVFs) are microvessels isolated from adipose tissue that are capable of improving tissue perfusion in a variety of tissue defects. The aim of this study was to determine whether the transplantation of MVFs in a dorsal rat skin flap model can improve flap survival. A 10 × 3 cm flap was raised in a cranial to caudal fashion on the dorsal side of 16 Lewis rats, with the caudal side remaining intact. The rats were equally divided into a treatment group (MVFs) and a control group (sterile saline). At the time of surgery, sterile saline with or without MVFs was injected directly into the flap. Microvessel density was determined after harvesting flap tissue by counting vessels that positively stained for Griffonia simplicifolia lectin I-isolectin B4. Laser Doppler was used to measure blood flow before and after surgery and 7 and 14 days later. Flap survival was evaluated 7 and 14 days after surgery by evaluating the percentage of viable tissue of the flap with photodigital planimetry. Despite the lack of a significant difference in microvessel density and tissue perfusion, flap survival increased 6.4% (P < 0.05) in MVF-treated animals compared with controls. The use of MVFs may be a means to improve flap survival. Future studies are required to delineate mechanisms whereby this occurs and to further optimize their application.


Mutation pattern in the genome of Neisseria gonorrhoeae and its association with multidrug-resistant isolates from Delhi, India.
Mutations in PenA, PorB, MtrE and MtrR genes responsible for antimicrobial resistance were checked in 27 drug-resistant clinical isolates of Neisseria gonorrhoeae (NG). Phenotype PIB (88.88%) and mutation at G120 and A121 positions of porB were recurrent. N122K, a novel mutation, was observed in PorB in three resistant isolates. Substitution H105Y in MtrR was widespread (37% of clinical isolates). The presence of a novel mutation (L33V), along with G45D mutation in MtrR, was associated with less-resistant isolates, in contrast to isolates with G45D mutation alone. African-type penicillinase-producing NG plasmid was observed most frequently (17/27) in penicillin-resistant isolates.


Restoration of colony-forming activity in osmotically stressed Escherichia coli by betaine.
Exposure of Escherichia coli to 0.8 M NaCl caused a rapid and large decrease in colony-forming activity. When such osmotically upshocked cells were exposed to betaine, colony-forming activity was restored. Betaine was able to restore colony-forming activity even when chloramphenicol inhibited protein synthesis. Thus, restoration was not the result of cell turnover. The cells were not killed by exposure to 0.8 M NaCl, because during exposure they accumulated ATP intracellularly. Betaine treatment caused this cellular ATP to decrease to a lower level. This work may provide the foundation for a simple plating procedure to quantitatively detect nonculturable E. coli in ocean beach recreational waters.


Reduced expression of antimicrobial PLUNC proteins in nasal polyp tissues of patients with chronic rhinosinusitis.
Chronic rhinosinusitis (CRS) is a disease characterized by inflammation of the nasal mucosa and paranasal sinuses. This inflammation may result in part from decreased epithelial barrier and innate immune responses, leading to frequent bacterial and fungal colonization. The objectives of this study were to investigate the expression of innate immune proteins of the palate lung and nasal epithelium clone (PLUNC) family in patients with CRS. Nasal tissue samples were collected from control subjects and CRS patients with and without nasal polyps. Expression of the members of the PLUNC family was analyzed by real-time PCR. Expression of SPLUNC1 and LPLUNC2 proteins was analyzed by ELISA, immunoblot, and immunohistochemical analysis. Levels of mRNA for most of the members of the PLUNC family were profoundly reduced in nasal polyps (NPs) compared to uncinate tissue from control subjects or patients with CRS. LPLUNC2 and SPLUNC1 proteins were decreased in NPs of patients with CRS compared to uncinate tissue from control subjects. Immunohistochemical data revealed that within submucosal glands of sinonasal tissues, SPLUNC1 and LPLUNC2 were differentially expressed, in serous and mucous cells, respectively. The decrease in the expression of these molecules is probably explained by a decrease in the number of glands in NPs as revealed by correlations with levels of the glandular marker lactoferrin. Decreased SPLUNC1 and LPLUNC2 in NPs reflect a profound decrease in the number of submucosal glands. Decreased glands may lead to a localized defect in the production and release of glandular innate defense molecules.


Molecular dynamics simulations reveal the conformational dynamics of Arabidopsis thaliana BRI1 and BAK1 receptor-like kinases.
The structural motifs responsible for activation and regulation of eukaryotic protein kinases in animals have been studied extensively in recent years, and a coherent picture of their activation mechanisms has begun to emerge. In contrast, non-animal eukaryotic protein kinases are not as well understood from a structural perspective, representing a large knowledge gap. To this end, we investigated the conformational dynamics of two key Arabidopsis thaliana receptor-like kinases, brassinosteroid-insensitive 1 (BRI1) and BRI1-associated kinase 1 (BAK1), through extensive molecular dynamics simulations of their fully phosphorylated kinase domains. Molecular dynamics simulations calculate the motion of each atom in a protein based on classical approximations of interatomic forces, giving researchers insight into protein function at unparalleled spatial and temporal resolutions. We found that in an otherwise "active" BAK1 the αC helix is highly disordered, a hallmark of deactivation, whereas the BRI1 αC helix is moderately disordered and displays swinging behavior similar to numerous animal kinases. An analysis of all known sequences in the A. thaliana kinome found that αC helix disorder may be a common feature of plant kinases.


Electron microscopic immunolocalization of a karyoskeletal protein of molecular weight 145 000 in nucleoli and perinucleolar bodies of Xenopus laevis.
Amplified nucleoli of Xenopus laevis oocytes contain a major karyoskeletal protein of Mr 145 000 insoluble in low- and high-salt buffer as well as in non-denaturing detergents. Electron microscopic localization on native and high-salt extracted nucleoli using specific murine antibodies against this polypeptide and gold-coupled antibodies for visualization reveals that the Mr 145 000 protein is located in coils of filaments of ca 4 nm diameter. In addition, this protein occurs in the medusoid filament bodies (MFBs) present in the nucleolar cortex and free in the nucleoplasm. In somatic cells of tissues and in A6 kidney epithelial cells grown in vitro the Mr 145 000 polypeptide or an immunologically related protein is also organized in coiled aggregates of filaments 4-12 nm in diameter present both in the periphery of nucleoli and free in the nucleoplasm. We discuss a possible role of this protein as a karyoskeletal support involved in the storage and transport of preribosomal particles.


Logistic Regression and Machine Learning Models for Predicting Whether Intensive Care Patients Who Are Alert and Without Delirium Remain As Such for at Least Two More Days.
Background Some intensive care unit patients are alert and without delirium for at least two consecutive days. These patients, like other critically ill individuals, are at risk for dignity-related distress. An interval of at least two days would provide for a palliative care multidisciplinary team to be consulted in the late morning or afternoon of day one and visit the next day. An assessment would include the administration of the validated Patient Dignity Inventory in a reflective manner. To determine whether dignity-related distress can be identified and treated during patients' intensive care unit stay, we evaluated whether a substantive fraction of such patients (≥5%) have a substantial (>90%) probability of remaining alert and without delirium in the intensive care unit for at least four consecutive days. Methods The retrospective cohort study used data from one large teaching hospital in the United States of America, from 2012 to June 2022. The inclusion criteria were: a) adults, b) present in an intensive care unit at 12 PM one day and continually so for the next 48 hours, c) during those two days had every Riker sedation-agitation scale score "4, calm and cooperative," and d) during those two days had all Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scores negative (i.e., no delirium) and all Delirium Observation Screening Scale (DOS) scores less than three (i.e., no delirium). Results Among the 10,314 patients alert and without delirium in an intensive care unit over two-day periods that included three successive 12 PMs, 3,826 (37%) maintained this status for at least two successive 12 PMs. Six patient characteristics (e.g., hemodynamic infusion or ventilatory support) had value in predicting those 37% of patients. However, logistic regression and classification models each predicted a few (≈0.2%) patients with >90% probability of maintaining these criteria. Forecasts were inaccurate for nearly all patients remaining alert and without delirium in the intensive care unit (≈37%) because the models predicted no patient alert, without delirium, and in the intensive care unit for two days would remain so for at least four days. That ≈63% accuracy was improved upon by random forest machine learning, but only with ≈3% improvement. Conclusion Although many intensive care unit patients remain alert and without delirium for several consecutive days, each patient has a high daily probability of intensive care unit discharge or deterioration in medical condition. Therefore, the results of our prediction modeling show that care models for the assessment and treatment of patients with intensive care unit-associated dignity-related distress should not rely solely on the intensive care unit team but instead should be taken from the perspective of the entire hospitalization.


Lithium niobate waveguide squeezer with integrated cavity length stabilisation for network applications.
We report a titanium indiffused waveguide resonator featuring an integrated electro-optic modulator for cavity length stabilisation that produces close to 5 dB of squeezed light at 1550 nm (2.4 dB directly measured). The resonator is locked on resonance for tens of minutes with 70 mW of SH light incident on the cavity, demonstrating that photorefraction can be mitigated. Squeezed light production concurrent with cavity length stabilisation utilising the integrated EOM is demonstrated. The device demonstrates the suitability of this platform for squeezed light generation in network applications, where stabilisation to the reference field is typically necessary.


Kinetics of fibrinogen and platelet adherence to biomaterials.
The initial task was to establish a conceptually and materially simple test procedure that could quantitate and evaluate the thrombogenic potential of a biomaterial surface. Since the primary events of thrombus formation on prosthetic surfaces are believed to involve the deposition of a plasma protein monolayer followed by platelet adhesion to its fibrinogen component, it seemed reasonable to focus on the binding kinetics of fibrinogen and platelets to a commonly used biomaterial. Employing solutions of 125I-fibrinogen in buffered saline, the adsorption characteristics of several types of biomedical tubing could be compared, and the competition and exchange among plasma proteins at surface binding sites of PVC were evaluated. Human platelets with 51Cr were found to adhere to PVC surfaces proportional to surface fibrinogen concentration, but only in the presence of plasma; the circulation of labelled platelets in buffered saline only resulted in significant adherence to the native surface, while surface fibrinogen was inhibitory. Physiological concentrations of albumin were the most effective in preventing both fibrinogen adsorption and platelet adherence. The most important consequence of this work, perhaps, is the many avenues of future experimentation discovered from this methodological approach, not only in the thrombogenic evaluation of a specific biomedical surface, but also in the delineation of thrombogenic sequelae in general.


Vitamin D, Hypercalciuria and Kidney Stones.
The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption-as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements.


Fruit tree leaves as valuable new source of tocopherol and tocotrienol compounds.
Nowadays it is highly important to find new, cheap and widely available sources of tocopherol and tocotrienol compounds, and leaves are promising unconventional sources. The main goal of this study was to extend the currently limited knowledge concerning tocopherol and tocotrienol isomers composition determined using ultra-high performance liquid chromatography with fluorescence detection analysis for various fruit tree leaves such as apple, pear, quince, apricot, peach, plum, sour cherry and sweet cherry. The leaves were collected 2 weeks after tree blooming and after fruit collection. Tocopherol and tocotrienol isomers were identified and quantified for the first time in all fruit tree leaves. The total tocopherol content ranged from 203.34 to 260.86 μg g-1 dry weight for spring leaves and from 23.83 to 235.62 μg g-1 dry weight for autumn leaves and consisted mainly of α-tocopherol. The rest of the isomers of tocopherol and tocotrienols were also found, but in trace amounts. A significantly lower content of tocopherols and tocotrienols was detected in leaves after autumn collection of fruits compared to leaves collected after blooming. Among the analyzed leaves, time collected and species were significantly more important than their cultivars. Regarding quantification analysis, apricot > peach > > plums > apples leaves were identified as the best sources of tocopherols, and sweet and sour cherry leaves exhibited a lower content. Fruit tree leaves are a novel significant source and good material for isolation of α-tocopherol for application in cosmetics, pharmaceuticals or in the food industry - for example, production of beverages or other functional foods. © 2021 Society of Chemical Industry.


Lack of usefulness of anti-transglutaminase antibodies in assessing histologic recovery after gluten-free diet in celiac disease.
Gluten-free diet (GFD) plays a key role in the treatment of celiac disease (CD), but it is difficult to evaluate the effect of GFD on the improvement of villous architecture using sensitive, non-invasive tests. Aim of this study is to evaluate anti-transglutaminase (tTG) antibodies in the follow-up of CD to detect histologic recovery. We studied 42 consecutive patients with CD. In all the patients anti-tTG antibodies (evaluated by the enzyme linked immunosorbent assay method) and EGDscopy with multiple bioptic samples before GFD and then 6, 12, and 18 months after GFD were evaluated. For comparison, a sorbitol H2-breath test (H2-BT) and anti-endomysium (EMA) antibodies test were carried out concomitantly. Anti-tTG results were positive in 36 of 42 patients before GFD (80.95%), while they were positive in 11 of 34 (32.35%), 1 of 17 (5.88%), and 0 of 6 (0%) of patients with a persistence in histologic lesions 6, 12, and 18 months of GFD respectively, without any correlation with persistence of histologic lesions (P = NS). Also EMA failed to show correlation with improvement of histologic lesions. They were positive in 31 of 42 patients before GFD (73.80%), while they were positive in 18 of 34 (52.94%), 3 of 17 (17.64%), and 0 of 6 (0%) cases 6, 12, and 18 months of GFD respectively (P = NS). Regarding sorbitol H2-BT, it was positive in 40 of 42 (95.24%) patients before GFD, while it was positive in 31 of 34 (91.17%), 13 of 17 (76.47%), and 4 of 6 (50%) of patients with a persistence in histologic lesions 6, 12, and then 18 months after GFD starting (see Fig. 2, infra). So, anti-tTG and EMA were ineffective in assessing the histologic recovery at each follow-up visit (P = NS), while sorbitol H2-BT seems more effective than anti-tTG and EMA in this field (P < 0.0001 sorbitol H2-BT versus anti-tTG and versus EMA at 18 months after gluten withdrawal). Thirty-eight of 42 (90.47%) patients adhered to a strict GFD. Four patients were found to have occasional dietary transgression, and in all we noted a progressive decreasing of anti-tTG after 6 months of GFD and negative anti-tTG after 12 months of GFD, but sorbitol H2-BT persisted being positive during the entire follow-up. Intestinal damage persisted during the follow-up, despite anti-tTG and EMA negativity, and worsened in the presence of dietary lapses. Anti-tTG does not seem effective to assess histologic recovery in the follow-up of celiac patients after they have started GFD due to its poor correlation with histologic damage.


Pathophysiology of GERD in China: the same factors at a lower scale.
Most of the factors involved in the pathogenesis of gastroesophageal reflux disease (GERD), previously described in European, Australian, and American studies, are present in Chinese patients with GERD, but at a lower scale. The acidity of gastric contents is reduced either spontaneously or by Helicobater pylori infection. A low-fat diet probably contributes to a more favorable gastric distribution of the meals, reduced obesity, and lowers the number of TLESRs. The prevalence of hiatal hernia is low and esophageal motility disorders are moderate. Like in Western countries, the pathophysiology of GERD in China is multifactorial, with variable combination of moderate abnormalities in individual patients, leading to milder forms of GERD.


Work engagement, psychological empowerment and relational coordination in long-term care: A mixed-method examination of nurses' perceptions and experiences.
Nurse engagement, empowerment and strong relationships among staff, residents and families, are essential to attract and retain a suitably qualified and skilled nursing workforce for safe, quality care. There is, however, limited research that explores engagement, empowerment and relational coordination in long-term care (LTC). Nurses from an older persons' mental health and dementia LTC unit in Australia participated in this study. Forty-one nurses completed a survey measuring psychological empowerment, work engagement and relational coordination. Twenty-nine nurses participated in individual interviews to further explore these concepts. Although nurses reported high psychological empowerment and work engagement, their relationships with key stakeholders varied. Our findings suggest that nurses in LTC require both supports and opportunities to contribute as active members of the multiprofessional care team that includes tailored education, professional development and positive interactions within the care team. Regular support is needed to enable nurses to feel empowered, foster relationships and communication, and facilitate work engagement. Based on these findings, we suggest that it is important to find ways to ensure that all who provide care perceive that they are part of the whole care team and able to contribute to the care and well-being of people in LTC.


Scientific Evidence and Controversies About Pioglitazone and Bladder Cancer: Which Lessons Can Be Drawn?
Pioglitazone, a peroxisome proliferator-activated receptors (PPAR) agonist, has been authorized for the management of type 2 diabetes since 1999 in the US and since 2000 in Europe. Since then, the risk of bladder cancer associated with pioglitazone use has been a serious concern. Following a warning from the Agence Française de Sécurité Sanitaire des Produits de Santé (Afssaps) [the French Agency for the Safety of Health Products], use of pioglitazone was suspended in France and Germany in June 2011. Elsewhere, restrictions on prescriptions were implemented, though for both the European Medicines Agency and the US Food and Drug Administration, the risk-benefit ratio remains favourable. Since the development of pioglitazone, its risk assessment has suffered from several inaccuracies such as its alleged specificity for the male rat, untrustworthy selective agonism for PPARγ and mistaken risk evaluation in the large PROactive trial (PROspective pioglitAzone Clinical Trial In macroVascular Events), where one case with a benign tumour in the placebo group was counted as a cancer case. It took until 2011 for the epidemiological data to be sufficiently numerous and conclusive to initiate application of safety measures. Today, the increased risk of bladder cancer associated with pioglitazone seems to be real, but the absolute risk is relatively low. However, in the context of weak efficacy in an extensive population of patients exposed to pioglitazone, the risk-benefit balance is now difficult to assess, and prescription restrictions do not ensure safety. For future risk management, the authors propose several suggestions, which involve an increasing role of health authorities and academic organizations.


Partial randomization design in a support group intervention study.
Randomized clinical trial (RCT) designs, in which participants are randomly assigned to treatment and control groups, are considered the gold standard of experimental design. However, if potential participants have a strong preference for a particular study group and/or when participatory effort must be sustained over a lengthy study time frame, they may deem randomization unacceptable, refuse to be in the study, and hence prevent the purpose of randomization from being realized. This article describes several alternative designs and the decision-making process prior to selecting a partially randomized preference trial (PRPT) design to accommodate preferences of women with breast cancer for participation in a support group intervention pilot study. Recruiting women into the two randomized arms of the PRPT was problematic because most potential participants expressed a preference for a particular study group. Possible reasons for failure to randomize more of the potential participants are discussed and suggestions for future research proposed.


Identification of autophagy-related risk signatures for the prognosis, diagnosis, and targeted therapy in cervical cancer.
To rummage autophagy-related prognostic, diagnostic, and therapeutic biomarkers in cervical cancer (CC). The RNA-sequence and clinical information were from the TCGA and GTEx databases. We operated Cox regression to determine signatures related to overall survival (OS) and recurrence-free survival (RFS) respectively. The diagnostic and therapeutic effectiveness of prognostic biomarkers were further explored. We identified nine (VAMP7, MTMR14, ATG4D, KLHL24, TP73, NAMPT, CD46, HGS, ATG4C) and three risk signatures (SERPINA1, HSPB8, SUPT20H) with prognostic values for OS and RFS respectively. Six risk signatures (ATG4C, ATG4D, CD46, TP73, SERPINA1, HSPB8) were selected for qPCR. We screened five prognostic signatures(ATG4C, CD46, HSPB8, MTMR14, NAMPT) with diagnostic function through the GEO database. Correlation between our models and treatment targets certificated the prognostic score provided a reference for precision medicine. We constructed OS and RFS prognostic models in CC. Autophagy-related risk signatures might serve as diagnostic and therapeutic biomarkers.


[Effects of hypothermia on cerebral oxygen metabolism in patients with mitral valve replacement].
To observe the effects of mild to moderate hypothermia on cerebral oxygen metabolism in patients with mitral valve replacement. Twenty patients undergoing mitral valve replacement were randomly divided in mild (30 ) and moderate (26 degrees Celsius) hypothermia groups. Under alpha stat, the oxygen content and the concentration of lactic acid in the radial artery and jugular venous bulb were monitored in patients undergoing mitral valve replacement at mild and moderate hypothermia respectively. The arterial-venous difference of oxygen content, oxygen uptake rate, and blood lactic acid levels in the cerebrum and total body were calculated. The effect of cardiopulmonary bypass (CPB) under the two hypothermia strategies on cerebral oxygen metabolism was analyzed. In the two groups, arterial-venous differences and oxygen uptake rates were both decreased after the commencement of cardiopulmonary bypass, and were rapidly elevated during rewarming. In mild hypothermia group, the arterial-jugular venous difference and oxygen uptake were higher than those in moderate hypothermia group (P<0.05) during CPB when the lowest temperature was reached. The concentration of lactic acid in the plasma was progressively increased in both groups during CPB. Arterial-venous difference in the oxygen content in both groups was still lower during CPB than before CPB(P<0.01). Mild and moderate hypothermia during CPB is sufficient to retain the balance of cerebral oxygen metabolism, and more intensive hypothermia may not ensure better cerebral protective effect. Cerebral oxygenation progressively increases after CPB under hypothermia, but whether imbalance of cerebral oxygen metabolism occurs needs further investigation.


Role of SpaO in the assembly of the sorting platform of a Salmonella type III secretion system.
Many bacterial pathogens and symbionts use type III secretion machines to interact with their hosts by injecting bacterial effector proteins into host target cells. A central component of this complex machine is the cytoplasmic sorting platform, which orchestrates the engagement and preparation of type III secreted proteins for their delivery to the needle complex, the substructure of the type III secretion system that mediates their passage through the bacterial envelope. The sorting platform is thought to be a dynamic structure whose components alternate between assembled and disassembled states. However, how this dynamic behavior is controlled is not understood. In S. Typhimurium a core component of the sorting platform is SpaO, which is synthesized in two tandemly translated products, a full length (SpaOL) and a short form (SpaOS) composed of the C-terminal 101 amino acids. Here we show that in the absence of SpaOS the assembly of the needle substructure of the needle complex, which requires a functional sorting platform, can still occur although with reduced efficiency. Consistent with this observation, in the absence of SpaOS secretion of effectors proteins, which requires a fully assembled injectisome, is only slightly compromised. In the absence of SpaOS we detect a significant number of fully assembled needle complexes that are not associated with fully assembled sorting platforms. We also find that although binding of SpaOL to SpaOS can be detected in the absence of other components of the sorting platform, this interaction is not detected in the context of a fully assembled sorting platform suggesting that SpaOS may not be a core structural component of the sorting platform. Consistent with this observation we find that SpaOS and OrgB, a component of the sorting platform, share the same binding surface on SpaOL. We conclude that SpaOS regulates the assembly of the sorting platform during type III secretion.


SARS-CoV-2-Specific IgG and IgA response in maternal blood and breastmilk of vaccinated naïve and convalescent lactating participants.
Recent studies have shown the presence of SARS-CoV-2-specific antibodies in the milk of breastfeeding mothers vaccinated with mRNA and convalescent. However, limited information is available in lactating women receiving other vaccine platforms used in developing countries, such as the inactivated SARS-CoV-2 vaccine BBIBP-CorV (Sinopharm) and the non-replicating adenovirus vaccines Sputnik V (Gamaleya Institute) and ChAdOx1-S (Oxford AstraZeneca). Here, we evaluated anti-SARS-CoV-2 IgG and IgA levels in both serum and milk samples using a longitudinal and a cross-sectional cohort of 208 breastfeeding vaccinated women from Argentina with or without previous SARS-CoV-2 infection. The analysis showed that IgA levels remain constant in serum and milk of breastfeeding mothers between the first and second doses of vector-based vaccines (Sputnik V and ChAdOx1-S). After the second dose, anti-spike IgA was found positive in 100% of the serum samples and in 66% of breastmilk samples. In addition, no significant differences in milk IgA levels were observed in participants receiving BBIBP-CorV, Sputnik V or ChAdOx1-S. IgG levels in milk increased after the second dose of vector-based vaccines. Paired longitudinal samples taken at 45 and 120 days after the second dose showed a decrease in milk IgG levels over time. Study of IgA levels in serum and milk of vaccinated naïve of infection and vaccinated-convalescent breastfeeding participants showed significantly higher levels in vaccinated-convalescent than in participants without previous infection. This study is relevant to understand the protection against SARS-CoV-2 by passive immunity in newborns and children who are not yet eligible to receive vaccination.


Heat shock response for ischemic kidney preservation and transplantation.
The heat shock response (HSR) is a form of stress conditioning during which reversible changes in cellular metabolism are rapidly induced by brief exposure to supra-physiologic levels of heat. The nature of these adaptive adjustments has been widely investigated and has received much attention in molecular biology and cancer research. Recent evidence indicates that a basic form of this stress response exists at the cellular level of virtually every organism. Although the physiological phenomenon of HSR is complex, it is well known that it can induce specific proteins, known as heat shock proteins (HSP's), which are not normally synthesized. HSP's become the major proteins synthesized during the heat shock response while normal protein synthesis is suppressed. In addition, the HSR has been demonstrated to confer a transient resistance to the organism to subsequent episodes of stress. Recently it has been reported that the HSR confers protection against cold ischemic injury and extends the cold preservation time of the rat kidney to 48 hours. In this study, we have applied the concept of HSR to the preservation, and transplantation of warm ischemically injured pig kidneys. Since there is a serious shortage of cadaver kidneys available for transplantation worldwide, this number would increase if warm ischemic kidneys could be utilized. However with present methods of organ recovery and preservation, such kidneys are not likely to function after transplantation even if they were removed. We hypothesized that the application of a thermal stress to pig kidneys prior to organ procurement and preservation will enhance the organs' ability to function after warm ischemic injury.


Noncoplanar and counterrotating incommensurate magnetic order stabilized by Kitaev interactions in γ-Li(2)IrO(3).
Materials that realize Kitaev spin models with bond-dependent anisotropic interactions have long been searched for, as the resulting frustration effects are predicted to stabilize novel forms of magnetic order or quantum spin liquids. Here, we explore the magnetism of γ-Li(2)IrO(3), which has the topology of a three-dimensional Kitaev lattice of interconnected Ir honeycombs. Using magnetic resonant x-ray diffraction, we find a complex, yet highly symmetric incommensurate magnetic structure with noncoplanar and counterrotating Ir moments. We propose a minimal Kitaev-Heisenberg Hamiltonian that naturally accounts for all key features of the observed magnetic structure. Our results provide strong evidence that γ-Li(2)IrO(3) realizes a spin Hamiltonian with dominant Kitaev interactions.


Patient crying during psychotherapy intake sessions: Relationship to patient characteristics and early treatment process.
The aim of the present study is to further the understanding of who cries at the beginning of psychotherapy and patients' experience of crying in that process. Intake sessions for 53 patients beginning psychotherapy at a university-based clinic were coded for discrete crying segments. Data about patient characteristics were also collected at intake. Results indicate that crying during intake sessions was related to lower global functioning and higher severity of childhood sexual abuse. Furthermore, patients who cried at intake were over four times more likely to also cry at feedback, and those who cried at feedback were almost 12 times more likely to have cried at intake. Finally, crying in the intake session did not appear to be related to patient- or therapist-rated working alliance. Overall, the present study provides valuable information about characteristics of patients who cry at the outset of the therapy process and patients' experience of crying over time in therapy. Findings suggest the need for further research on patient characteristics and aspects of the therapy process that may predict patient crying over the course of treatment, as well as how these early crying experiences may be related to eventual patient outcomes.


Colorectal cancer in an African city population in transition.
An enquiry has been made on a series of African patients with colorectal cancer who were admitted in 1995-1999 to Chris Hani Baragwanath Hospital (3200 beds), and who lived in Soweto (population about 1 million), Johannesburg, South Africa. In the urban context described, Africans have considerably more advantages, socio-economically, dietarily and in other respects, than their rural counterparts. The 126 patients comprised 58 males and 68 females, giving calculated incidence rates in their communities for colorectal cancer of 1.7 and 2.0, respectively, per 100,000 'world' population. In contrast, as indicated in the South African Cancer Registry for 1993-1995, the corresponding rates for white males and females were 24.7 and 19.3, respectively, per 100,000. The proportion of African patients under 40 years was 19.0%; but was only 4.0% in the white population. In contrast to this major disparity, there was only a minor interethnic disparity regarding cancers that are very common in Africans, namely, those of the oesophagus and lung. Hence, with ongoing transitional changes - in diet and other respects - the relatively high proportion of younger African patients probably indicates a rising occurrence of colorectal cancer in the urban African population.


Regioselective Intermolecular Diamination and Aminooxygenation of Alkenes with Saccharin.
Palladium catalysis enables the regioselective difunctionalization of alkenes using saccharin as the nitrogen source in the initial step of aminopalladation. Depending on the reaction conditions, diamination or aminooxygenation pathways can be accessed using hypervalent iodine reagents as the terminal oxidants. The aminooxygenation of allylic ethers originates from an unprecedented ambident behavior of saccharin. The participating palladium catalysts contain a palladium-saccharide unit. Two representative complexes of this type could be isolated and characterized.


Dynamic protein and polypeptide hydrogels based on Schiff base co-assembly for biomedicine.
Stimuli-responsive biopolymer hydrogels are promising building blocks for biomedical devices, attributable to their excellent hydrophilicity, biocompatibility, and dynamic responsiveness to temperature, light, pH, and water content. Although hydrogels find interesting applications as drug carriers, therapeutic adhesives, scaffolds for tissue engineering, inks for bioprinting, and biosensors, conventional chemically crosslinked hydrogels often lack adaptive and biomimetic properties needed for diverse biomedical applications. Using dynamic and reversible crosslinks such as the Schiff base bond, biomimetic hydrogels featuring structurally dynamic behaviours, such as shape memory, self-healing properties, and dynamic mechanical resilience, can be developed for in vivo therapy. Natural proteins and polypeptides are non-toxic, biodegradable, and biocompatible biopolymers that serve fundamental structural and biochemical functions in the human body. Besides natural polypeptides, easily processible synthetic polypeptides are protein analogues with widely tunable sequences that form secondary structures. Therefore, natural proteins and synthetic polypeptides are excellent candidates for fabricating Schiff base-linked biomedical hydrogels. This review outlines the functional properties, design approaches, and applications of Schiff base-linked protein and polypeptide hydrogels in tissue engineering, regenerative medicine, wound dressing, drug delivery, bioprinting, and biosensors. The review ends with an outlook of future developments for potential applications of Schiff base-linked protein and polypeptide hydrogels in and beyond biomedicine.


X-ray microanalysis of aldehyde-fixed glycogen contrast-stained by OsVI . FeII and OsVI . RuIV complexes.
The composition of the contrast-donating complex of rat liver glycogen, nucleoplasm, erythrocytes, and mitochondria was established by X-ray microanalysis. In these compartments the presence of osmium and iron was shown qualitatively in tissue after glutaraldehyde fixation, treated with OsVIIIO4 plus K4FeII(CN)6 and in similar tissue treated with a combination of K2OsVIO4 plus K4FeII(CN)6. Osmium and ruthenium were detected in these compartments, in aldehyde-fixed tissue treated with mixtures containing K2RuIVL(CN)6 rather than K4FeII(CN)6. The iron detected in the glycogen, nucleoplasm, erythrocytes, and mitochondria of tissue treated with K2RuIV(CN)6 mixtures proved to derive from sources inside the electron microscope, and had to be considered an artifact. Quantitatively, the mean atomic ratios of osmium-to-iron and osmium-to-ruthenium were determined from spectra obtained by point analyses of the same compartments (glycogen, nucleoplasm, mitochondria, lipid droplets, and erythrocytes). After correction of the spectra for the instrumental iron contribution, the osmium-to-iron and osmium-to-ruthenium ratios in the glycogen were about 1:3 for tissue treated with those combinations including K2OsVIO4. In the other compartments, the osmium-to-iron and osmium-to-ruthenium ratios were virtually 1:0. For Os-VIIIO4 in combination with potassium ferrouscyanide however the osmium-to-iron ratio was 1:7 in the glycogen and 1:5 in all other compartments. OsVIIIO4 was combined with potassium ruthenium-cyanide, the osmium-to-ruthenium ratio was 1:2 in the glycogen and 2:1 in the other compartments. These results support our view that the selective glycogen contrast is obtained by complex formation.


Quadratic scaling bosonic path integral molecular dynamics.
Bosonic exchange symmetry leads to fascinating quantum phenomena, from exciton condensation in quantum materials to the superfluidity of liquid 4He. Unfortunately, path integral molecular dynamics (PIMD) simulations of bosons are computationally prohibitive beyond ∼100 particles, due to a cubic scaling with the system size. We present an algorithm that reduces the complexity from cubic to quadratic, allowing the first simulations of thousands of bosons using PIMD. Our method is orders of magnitude faster, with a speedup that scales linearly with the number of particles and the number of imaginary time slices (beads). Simulations that would have otherwise taken decades can now be done in days. In practice, the new algorithm eliminates most of the added computational cost of including bosonic exchange effects, making them almost as accessible as PIMD simulations of distinguishable particles.


[111In-DTPA-D-Phe1]-octreotide scintigraphy in patients with hormone-refractory prostatic adenocarcinoma can predict therapy outcome with octreotide treatment: a pilot study.
A pilot study to evaluate the predictive value of Indium-111-labelled somatostatin analogue [DTPA-D-Phe1]-octreotide scintigraphy (OctreoScan111) in the Octreotide treatment of hormone-refractory prostatic adenocarcinoma was initiated. Ten patients were investigated with OctreoScan111 with regard to disease extension and tumor-to-background ratio. Subsequently, the patients were treated with Octreotide (Sandoz, Basel, Schweiz) at a dose of 100 micrograms twice a day subcutaneously. Three patients experienced symptomatic relief, and two of these responded with a decrease in PSA. Three patients did not notice any difference after 6 months of treatment and two of them developed an increase in their PSA value. One patient progressed after five months as regards both PSA and symptoms. Three patients were not able to complete treatment. Of the seven evaluable patients, the three with the highest tumour-to-background ratios at OctreoScan111 were those patients with reduced or stable PSA levels, and none of these progressed during treatment. Previous reports along with this study demonstrate that only a minority of patients with hormone-refractory prostatic adenocarcinoma benefit from Octreotide treatment. However, OctreoScan111 investigations may identify patients who will respond to Octreotide therapy.


Establishing a reproducible protocol for measuring index active extension strength.
The goal of this study was to establish a reproducible protocol to measure active extension strength in the index finger. The secondary objectives consisted in correlating the independent or associated index extension strength to the other fingers force of contraction of the extensor indicis propius with hand dominance. The population studied consisted of 24 healthy volunteers, including 19 women and 20 right-handed individuals. The independent and dependent index extension strength in each hand was measured three times with a dynamometer by three examiners at Day 0 and again at Day 7. Intra and inter-examiner reproducibility were, respectively, >0.90 and >0.75 in all cases. The independent extension strength was lower than the dependent one. There was no difference between the independent index extension strength on the dominant and non-dominant sides. The same was true for the dependent strength. Our results show that our protocol is reproducible in measuring independent and dependent index extension strength. Dominance did not come into account. II.


A Membrane-Based Process for the Recovery of Glycyrrhizin and Phenolic Compounds from Licorice Wastewaters.
In this work, the use of polymeric ultrafiltration and nanofiltration membranes was investigated in order to recover glycyrrhizin and phenolic compounds from licorice wastewaters. Filtration experiments were performed on a laboratory scale using four polyamide thin-film composite membranes (GK, GH, GE, and DK, from GE Osmonics) with different molecular weight cut-offs (from 150 to 3500 Da). The permeate flux and retention values of glycyrrhizin, the total polyphenols, the caffeic acid, the total carbohydrate, and the total antioxidant activity as a function of the transmembrane pressure (TMP) and weight reduction factor (WRF) were evaluated. In selected operating conditions, the membrane productivity decreased in the order of GK > DK > GH > GE, with a similar trend to that of water permeability. Glycyrrhizin was totally rejected by selected membranes, independently of TMP and WRF. For the other antioxidant compounds, the retention values increased by increasing both of the parameters. According to the experimental results, a combination of membranes in a sequential design was proposed as a viable approach to produce concentrated fractions enriched in bioactive compounds and purified water from licorice wastewater.


No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis.
A double-blind randomized study was performed to evaluate the effect of oral ribose supplementation on repeated maximal exercise and ATP recovery after intermittent maximal muscle contractions. Muscle power output was measured during dynamic knee extensions with the right leg on an isokinetic dynamometer before (pretest) and after (posttest) a 6-day training period in conjunction with ribose (R, 4 doses/day at 4 g/dose, n = 10) or placebo (P, n = 9) intake. The exercise protocol consisted of two bouts (A and B) of maximal contractions, separated by 15 s of rest. Bouts A and B consisted of 15 series of 12 contractions each, separated by a 60-min rest period. During the training period, the subjects performed the same exercise protocol twice per day, with 3-5 h of rest between exercise sessions. Blood samples were collected before and after bouts A and B and 24 h after bout B. Knee-extension power outputs were approximately 10% higher in the posttest than in the pretest but were similar between P and R for all contraction series. The exercise increased blood lactate and plasma ammonia concentrations (P < 0.05), with no significant differences between P and R at any time. After a 6-wk washout period, in a subgroup of subjects (n = 8), needle-biopsy samples were taken from the vastus lateralis before, immediately after, and 24 h after an exercise bout similar to the pretest. ATP and total adenine nucleotide content were decreased by approximately 25 and 20% immediately after and 24 h after exercise in P and R. Oral ribose supplementation with 4-g doses four times a day does not beneficially impact on postexercise muscle ATP recovery and maximal intermittent exercise performance.


Acute Post Surgical Pain may result in chronic post surgical pain: A Systemic Review and Meta Analysis.
Chronic post surgical pain (CPSP) occurres frequently (from 10% to 50%) and has serious effects on the mood and activities of patients. This study was designed to evaluate the relationship between acute post surgical pain and chronic post surgical pain. Electronic search databases included PubMed, EMBASE, Cochrane database and web of science. 9-stars Newcastle-Ottawa Scale was used to evaluate the quality of included studies. The odds ratio was used as a summary statistic index. Heterogeneity was assessed with I (2). We collected data from 4 case-control studies with or without chronic post surgical pain and compared those with patients who had acute post surgical pain or not. The age, sex was controlled as confounding factors. We collected 765 patients with chronic post surgical pain, of which 38.82% used to have acute post surgical pain. The risk ratio of patients with acute post surgical pain, as compared with no acute post surgical pain, was 3.10 for chronic post surgical pain (95% CI: 2.44, 3.96). Acute post surgical pain is a rick factor for chronic post surgical pain. We need to pay much attention to this phenomenon. However, more studies with high quality were still needed to confirm these findings.


Changes in calcium and phosphate and their regulating hormones in patients with severe burn injuries.
Changes in the calcium- and phosphate homeostasis and its regulating hormones calcitonin (CT) and parathyroid hormone (PTH) are of great importance for several pathophysiological reactions after trauma. In this study calcium, phosphate, CT, PTH and nor-adrenaline, were followed during 14 days after trauma in 20 patients with severe burn injuries. The results showed significantly reduced serum phosphate (S-P) during the first week after trauma, and low ionized calcium fraction (CaF) during the 14 post-traumatic days that were studied. Urinary calcium output was low, about 4.5 mmol/day and urinary phosphate output was as high as 30 mmol/day, despite the low S-P. Plasma nor-adrenaline was elevated with maximum concentrations 6 days after trauma. CT was very high with levels around 1 000 pmol/l after one week. PTH remained within the reference interval, although a statistically significant increase was observed four days after the trauma. The results suggest that the observed changes in calcium- and phosphate homeostasis were related to the humoral response to trauma.


Soret coefficient of the n-dodecane-n-hexane binary mixture under high pressure.
In the present work, the Soret coefficient has been determined at high pressure for a binary hydrocarbon mixture by combining the thermogravitational column and the dynamic near-field imaging techniques. The analyzed mixture is an iso-massic n -dodecane-n -hexane mixture at 298.15K. The molecular diffusion coefficient has been measured up to 20MPa by means of the dynamic analysis of the light scattered by non-equilibrium concentration fluctuations. With a cylindrical thermogravitational column the thermodiffusion coefficient was determined from 0.1MPa to 10MPa. Density, as well as, mass expansion and thermal expansion have been measured with a high pressure densimeter. Dynamic viscosity at up to 20MPa has been determined with a high pressure viscometer. This work shows the decreasing tendency of both the molecular diffusion and the thermodiffusion coefficient with increasing pressure.


Climatic refugia and reduced extinction correlate with underdispersion in mammals and birds in Africa.
Macroevolutionary patterns, often inferred from metrics of community relatedness, are often used to ascertain major evolutionary processes shaping communities. These patterns have been shown to be informative of biogeographic barriers, of habitat suitability and invasibility (especially with regard to environmental filtering), and of regions that function as evolutionary cradles (i.e., sources of diversification) or museums (i.e., regions of reduced extinction). Here, we analyzed continental datasets of mammal and bird distributions to identify primary drivers of community evolution on the African continent for mostly endothermic vertebrates. We find that underdispersion (i.e., relatively low phylogenetic diversity compared to species richness) closely correlates with specific ecoregions that have been identified as climatic refugia in the literature, regardless of whether these specific regions have been touted as cradles or museums. Using theoretical models of identical communities that differ only with respect to extinction rates, we find that even small suppressions of extinction rates can result in underdispersed communities, supporting the hypothesis that climatic stability can lead to underdispersion. We posit that large-scale patterns of under- and overdispersion between regions of similar species richness are more reflective of a particular region's extinction potential, and that the very nature of refugia can lead to underdispersion via the steady accumulation of species richness through diversification within the same ecoregion during climatic cycles. Thus, patterns of environmental filtering can be obfuscated by environments that coincide with biogeographic refugia, and considerations of regional biogeographic history are paramount for inferring macroevolutionary processes.


Factors affecting general practitioner involvement in a randomised controlled trial in primary care.
To investigate factors associated with patient recruitment by general practitioners (GPs) in a randomised controlled trial in primary care. Cross sectional survey of 100 GPs who had agreed to recruit patients for a randomised controlled trial. A postal questionnaire was sent to the 100 GPs to collect information on factors associated with recruitment in the randomised controlled trial. The response rate to the survey was 97%. GPs who reported that practice nurses were involved in the research project were significantly more likely to recruit patients into the trial. Age, sex, membership of an independent practitioner association (IPA), number of half days worked, and the number of GPs working in a practice were not associated with recruitment. Involvement of practice nurses together with GPs may improve recruitment of patients in randomised controlled trials in primary care in New Zealand.


Piccolo mediates EGFR signaling and acts as a prognostic biomarker in esophageal squamous cell carcinoma.
The presynaptic cytomatrix protein Piccolo, encoded by PCLO, is frequently mutated and amplified in esophageal squamous cell carcinoma (ESCC), but its exact roles in ESCC remain unclear. Here we report that Piccolo expression correlates significantly with clinical stage, patient survival and tumor embolus. Functional studies demonstrate that PCLO knockdown remarkably attenuates ESCC malignancy in vitro and in vivo, and ectopic EGFR expression partially compensates for Piccolo loss. PCLO knockdown promotes ubiquitination and degradation of EGFR, which is associated with the negative regulatory effect of Piccolo on E3 ligase Siah1. An anti-Piccolo monoclonal antibody inhibited tumor proliferation in a mouse model of ESCC. These results demonstrate that Piccolo contributes to tumor aggressiveness in ESCC, likely by stabilizing EGFR and promoting EGFR-dependent signaling. Our results further suggest that Piccolo may represent a novel prognostic biomarker and therapeutic target for patients with ESCC.