Epidemiology and prevention of Staphylococcus aureus nasal carriage in hemodialyzed patients.
Nasal carriage of Staphylococcus aureus may be responsible for some serious infections among hemodialyzed patients. Its pathogenic potential and commensal nature allows for an easy transmission both in and out of hospital environment. This study was to assess the prevalence of S. aureus nasal carriage, to determine its frequency and nature in hemodialyzed patients of the Rabat Ibn Sina University hospital, in Morocco. The study began in March 2008 according to the following protocol: screening of nasal carriage with five samplings, performed once a month three times, then once a month two times again after an interruption period of three months. Screening was performed weekly during the first month in hemodialyzed patients treated with mupirocin (Bactroban(®) 2%), and then monthly, to monitor the kinetics of S. aureus eradication. The study included 54 hemodialyzed patients with a mean 44.16±14 years of age, sex ratio of 0.54, and mean hemodialysis duration of 118.7±67 months. Permanent and intermittent S. aureus carriage was found in respectively 18.52% and 25.92% of patients. Eighty-one strains of S. aureus were identified, 14.81% of which were methicillin resistant. Eradication was sustained beyond 20 months in patients treated with mupirocin. This investigation allowed us to identify hemodialyzed patients at risk, so as to implement the rules of individual and collective hygiene, and to extend mupirocin antibiotic prophylaxis in our hemodialysis unit.


Oestrogen and progesterone reduce lipopolysaccharide-induced expression of tumour necrosis factor-alpha and interleukin-18 in midbrain astrocytes.
Besides microglia, astrocytes exert an important regulatory function in the initiation and control of neuro-inflammatory processes in the central nervous system. Clinical and experimental data suggest that sex steroids are neuroprotective and that neurological/neurodegenerative disorders display sex-specific characteristics. Astroglia is known to respond to toxic stimuli by secretion of distinct pro-inflammatory/apoptotic cytokines. In the present study, we investigated the influence of oestrogen and progesterone on the expression of the cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-18 in primary astrocytes obtained from neonatal mouse midbrain and cerebral cortex after the stimulation with lipopolysaccharides (LPS). LPS strongly induced the expression of TNF-alpha in astrocytes from both brain regions and IL-18 in those from midbrain. Oestrogen significantly attenuated LPS-induced TNF-alpha expression in the midbrain glia but not in the cortex glia. Combined treatment with oestrogen and progesterone together diminished LPS-induced IL-18 expression in the midbrain completely. Both steroid effects could be specifically antagonised by the steroid hormone receptor antagonists ICI 182 780 and mifepristone. We conclude that neuroprotective oestrogen and progesterone effects in the midbrain might be in part the consequence of a reduced pro-inflammatory response of astroglia.


Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects.
Vaspin (visceral adipose tissue-derived serpin) was first identified as an adipokine in a rat model of type 2 diabetes, in which it is predominantly secreted from visceral adipose tissue. Serum concentrations of vaspin show a food intake-related diurnal variation. We therefore tested the hypothesis that vaspin plays a role in the regulation of food intake. Vaspin levels in the hypothalamus and human stomach were determined by western blotting. The cerebrospinal fluid concentration of vaspin was measured in five healthy volunteers using an ELISA. Fed 11-week-old female db/db mice were given intraperitoneal injections of 1 mg/kg body weight of vaspin (n = 6) or saline (n = 6) on experimental days 1, 3 and 4. Changes in food intake and fed plasma glucose concentrations were determined after one intracerebroventricular administration of either 1 μg vaspin or artificial cerebrospinal fluid into 11-week-old female db/db (n = 8) and C57BL/6 mice (n = 8) up to 6 days after injection. We detected vaspin in the hypothalamus of db/db and C57BL/6 mice and in the cerebrospinal fluid of healthy individuals. Both peripheral and central vaspin administration decrease food intake in obese db/db and lean C57BL/6 mice. In db/db mice, vaspin treatment is associated with sustained glucose-lowering effects for at least 6 days after injection. In addition, we demonstrated expression of the gene encoding vaspin in the gastric mucosa in humans, and found that this was subject to regional variations. Our data suggest a previously unrecognised role of vaspin in the regulation of food intake. We postulate that vaspin inhibits a protease that degrades an anti-orexigenic factor.


Immunochemical detection of unrepaired cyclobutane-type pyrimidine dimers of DNAs extracted from human skin tumours.
Unrepaired cyclobutane-type pyrimidine dimers of DNA extracted from human skin tumours were examined by an immunoblotting method using polyclonal antibodies raised against UV-irradiated calf thymus DNA. A total of 40 DNA samples extracted from seven SCC lesions, two AK lesions, two lymphomas, one basal cell epithelioma, one eccrine poroma, one neurofibroma of Recklinghausen's disease, on verruca vulgaris, four femoral normal skins and white blood cells of 21 humans were studied by immunoblotting using this antibody. Two of the 40 DNAs examined, one from facial actinic keratosis (AK) and one from a squamous cell carcinoma (SCC) which developed form facial AK formed immunoprecipitates. It was found, using photoreactivation enzyme plus visible light, that both immunoprecipitates were cyclobutane-type pyrimidine dimers. In addition, immunofluorescent studies on AK tissue were positive in an immunoblotting assay and revealed that the unremoved photodamage in DNA remained in the nucleus of AK cells. These findings indicate that these tumour cells may be deficient in the enzyme function for repairing photoproduct damage. The unrepaired cyclobutane-type pyrimidine dimer in AK cells might reflect the genetic process in multistage carcinogenesis as well as in xeroderma pigmentosum.


Seroepidemiological study of the immune response to Campylobacter pylori in potential risk groups.
To gain more understanding of the epidemiology of Campylobacter pylori infection, the immune response to the organism was studied in the following selected potential risk groups: endoscopy staff (n = 45), dental staff (n = 58), orphanage children (n = 24), psychiatric patients (n = 58), and family contacts of Campylobacter pylori-infected patients (n = 55). The frequency of an IgG and IgA antibody response in the different groups was determined by the immunoblot method and compared with that in an appropriate control group (n = 189). The frequency of a positive antibody response was dependent on age (p less than 0.0001) but not on sex. When results were corrected for age by logistic regression analysis, all groups, with the exception of dental staff and orphanage children, revealed a significantly raised frequency of an IgA and combined IgG/IgA immune response compared to controls. There was not a significant difference for the IgG response, except in orphanage children. It is concluded that endoscopy staff, family contacts of Campylobacter pylori-infected patients and people living in closed communities such as psychiatric patients and orphanage children must be considered as risk groups for Campylobacter pylori infection. The findings support the notion that person-to-person spread and a common source are the predominant modes of transmission of Campylobacter pylori in addition to endoscopes.


Predictive factors for malignant pheochromocytoma: analysis of 136 patients.
We evaluated the clinical characteristic, tumor feature and immunohistochemistry factors predicting malignant pheochromocytoma. Between January 1999 and December 2008 we retrospectively reviewed the records of 136 patients with pheochromocytoma at Ruijin Hospital. We compared clinical characteristics (age, gender, symptoms and biochemical analysis), tumor features (site, weight and diameter) and the expression of 3 angiogenesis/metastasis related genes (VEGF, Cox-2 and MVD) by immunohistochemical analysis of benign vs malignant pheochromocytomas. Of the 136 patients 105 (77%) had benign and 31 (23%) had malignant pheochromocytoma. Malignant tumors were larger and heavier than benign tumors, and accompanied by higher plasma metanephrine secretion (each p <0.001). Mean tumor catecholamine and preoperative 24-hour urinary metanephrine or normetanephrine were obviously higher in malignant than in benign tumors (p <0.001). Also, 25 malignant tumors (81%) were immunopositive for VEGF while only 24 benign tumors (23%) showed this characteristic (p <0.001). Microvessel density and the rate of positive staining for Cox-2 protein in malignant samples were higher than in benign samples (p <0.001). Several promising predictive parameters are currently available to distinguish benign from malignant pheochromocytoma. Large (5 cm or greater) or heavy (250 gm or greater) tumors, multifocal and extra-adrenal tumors, early onset postoperative hypertension and higher plasma or urine metadrenaline are high risk factors predictive of malignant pheochromocytoma. Also, expression of the 3 angiogenesis or metastasis related genes VEGF, Cox-2 and MVD helps determine the diagnosis of malignancy and suggests strict followup.


Enhancement of hippocampal-thalamocortical temporal coordination during slow-frequency long-duration anterior thalamic spindles.
Temporal nesting of cortical slow oscillations (SO), thalamic spindles and hippocampal ripples indicates multi-regional neuronal interactions required for memory consolidation. However how the thalamic activity during spindles organizes hippocampal dynamics remains largely undetermined. We analyzed simultaneous recordings of anterodorsal thalamus and CA1 in male mice to determine the contribution of thalamic spindles in cross-regional synchronization. Our results indicated that temporal hippocampo-thalamocortical coupling were more enhanced during slower and longer thalamic spindles. Additionally, spindles occurring closer to SO trough were more strongly coupled to ripples. We found that the temporal association between CA1 spiking/ripples and thalamic spindles was stronger following spatial exploration compared to baseline sleep. We further developed a hippocampal-thalamocortical model to explain the mechanism underlying the duration and frequency-dependent coupling of thalamic spindles to hippocampal activity. Our findings shed light on our understanding of the functional role of thalamic activity during spindles on multi-regional information transfer.Significance Statement:The contribution of thalamic spindles with differential properties to cross-regional synchronization and information transfer still remains poorly understood. Using simultaneous anterodorsal thalamic and hippocampal recordings from naturally sleeping mice before and after exploration, we found strong coupling of CA1 units to anterodorsal thalamic spindles and increase of this coupling following spatial experience. We further showed that the temporal coupling of CA1 units and hippocampal ripples with thalamic spindles and the spindle-associated modulation of CA1 units with ripples were stronger for spindles with slower frequency of oscillations. Our experimental as well as computational findings using a hippocampal-thalamocortical model provide the first demonstration that spindle frequency and duration can provide valuable information about the underlying multi-regional interactions essential for memory consolidation computations.


Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia.
Tissue acidosis is effective in causing chronic muscle pain. However, how muscle nociceptors contribute to the transition from acute to chronic pain is largely unknown. Here we showed that a single intramuscular acid injection induced a priming effect on muscle nociceptors of mice. The primed muscle nociceptors were plastic and permitted the development of long-lasting chronic hyperalgesia induced by a second acid insult. The plastic changes of muscle nociceptors were modality-specific and required the activation of acid-sensing ion channel 3 (ASIC3) or transient receptor potential cation channel V1 (TRPV1). Activation of ASIC3 was associated with increased activity of tetrodotoxin (TTX)-sensitive voltage-gated sodium channels but not protein kinase Cϵ (PKCϵ) in isolectin B4 (IB4)-negative muscle nociceptors. In contrast, increased activity of TTX-resistant voltage-gated sodium channels with ASIC3 or TRPV1 activation in NaV1.8-positive muscle nociceptors was required for the development of chronic hyperalgesia. Accordingly, compared to wild type mice, NaV1.8-null mice showed briefer acid-induced hyperalgesia (5 days vs. >27 days). ASIC3 activation may manifest a new type of nociceptor priming in IB4-negative muscle nociceptors. The activation of ASIC3 and TRPV1 as well as enhanced NaV1.8 activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain.


Enhancement of tumorigenicity of human breast adenocarcinoma cells in nude mice by matrigel and fibroblasts.
The failure of MCF7 cells to induce the formation of tumours after sub-cutaneous inoculation into athymic nude mice can be obviated by the simultaneous injection of an extract of basement membrane proteins (matrigel). Tumour growth is promoted and the latency period is low (2 to 4 weeks). In the absence of matrigel, the simultaneous inoculation of fibroblasts and MCF7 cells also resulted in the development of tumours, but with a longer latency period (about 2 months). The tumorigenic synergy between matrigel and fibroblasts was evidenced by co-inoculating MCF7 cells MDA-MB 231 cells with fibroblasts and matrigel. This co-inoculation decreased the delay of appearance of the tumours and/or accelerated the tumour growth, depending upon the number of fibroblasts injected. Repeated injections of fibroblasts conditioned medium, at the site of inoculum of tumour cells also enhanced tumour growth, suggesting the involvement of soluble factors secreted by fibroblasts. Histologically, tumours induced by co-inoculation of tumour cells and fibroblasts contained more stromal structures including vimentin-positive cells, fibronectin and interstitial collagens. These data suggest that human tumours may be reconstituted and grown in athymic nude mice using basement membrane components and fibroblasts as inductors.


Expression of key mTOR pathway components in pancreatic ductal adenocarcinoma: A multicenter study for clinicopathologic and prognostic significance.
Thus far, clinicopathologic and prognostic significance of mTOR signaling pathway in pancreatic ductal adenocarcinoma (PDAC) remains unclear, although it is involved in PDAC. In this study, total (t-) and phosphorylated (p-) mTOR, 4EBP1 and P70S6K, were investigated. It was found that most aforementioned proteins were related to malignant and progressive phenotypes, especially histological grade, in independent development and validation cohorts of PDAC. In the development cohort, high expression and/or phosphorylation of mTOR, 4EBP1 and P70S6K were all univariately associated with poor tumor-specific survival, whereas p-mTOR, p-4EBP1 and p-P70S6K, adjusted for clinicopathologic variables, unlike t-mTOR, t-4EBP1 and t-P70S6K, were shown to be independent prognostic factors in multivariate analysis. Interestingly and importantly, the independently significant impacts of p-mTOR and p-4EBP1 on tumor-specific survival were confirmed in the validation cohort. Contrarily, t-mTOR and t-4EBP1 were only univariately significant, while t-P70S6K and p-P70S6K were not prognostic. Finally, mTOR and EIF4EBP1, genes encoding mTOR and 4EBP1, also serve as prognostic indicators in the publicly available TCGA RNA-sequencing database. Our data indicate that expression and activation, especially the latter, of mTOR and 4EBP1, might have clinicopathologic and prognostic significance in PDAC.


MARTINI bead form factors for the analysis of time-resolved X-ray scattering of proteins.
Time-resolved small- and wide-angle X-ray scattering (SAXS and WAXS) methods probe the structural dynamics of proteins in solution. Although technologically advanced, these methods are in many cases limited by data interpretation. The calculation of X-ray scattering profiles is computationally demanding and poses a bottleneck for all SAXS/WAXS-assisted structural refinement and, in particular, for the analysis of time-resolved data. A way of speeding up these calculations is to represent biomolecules as collections of coarse-grained scatterers. Here, such coarse-graining schemes are presented and discussed and their accuracies examined. It is demonstrated that scattering factors coincident with the popular MARTINI coarse-graining scheme produce reliable difference scattering in the range 0 < q < 0.75 Å-1. The findings are promising for future attempts at X-ray scattering data analysis, and may help to bridge the gap between time-resolved experiments and their interpretation.


Negative Homotropic Cooperativity in Guest Binding of a Trisporphyrin Double Cleft.
The negative homotropic allostery of a triple-layered trisporphyrin cleft with two guest binding sites is confirmed. The X-ray crystal structures of the 1 : 2 host-guest complexes showed that the trisporphyrin accommodated two guest molecules within the cleft through π-π stacking and donor-acceptor interactions. In solution, 1 H NMR and Job plots showed 1 : 2 host-guest complexes. Isothermal titration calorimetry (ITC) and UV/vis absorption spectroscopy were employed to evaluate the binding constants and cooperativities. The guest binding of the trisporphyrin showed negative cooperativity and non-cooperativity depending on the structures of the guest molecules. The correlations between the interaction parameters (α) and Hill constants were determined. ITC experiments showed that the host-guest complexation of trisporphyrin with electron-deficient guests incurred an enthalpy penalty in the successive guest binding process. DFT calculations revealed that binding of the first guest reduced the electron density of the central porphyrin plane, which led to an energetic penalty that weakened the successive binding process.


Antiphospholipid antibody syndrome and LVAD: What are the chances? A case report and literature review.
Left-ventricular-assist-device (LVAD) implantation in patients with antiphospholipid-syndrome (APS) is considered a high-risk procedure and its indication still represents an open challenge. Herein, we report a 63-year-old man with APS and end-stage heart failure, for whom a HeartMate3-LVAD and a continuous rheologic profile monitoring with a multiparametric assessment resulted the optimal therapeutic strategy.


The analysis of lacquer crack in the assessment of myopic choroidal neovascularization.
The aim of this study was to clarify the characteristic findings in myopic choroidal neovascularization (CNV) and the relationship with lacquer crack (LC). In all, 66 consecutive myopic CNV patients treated with photodynamic therapy and/or intravitreal anti-vascular endothelial growth factor injection in one eye were reviewed. Data from fluorescein angiography (FA) and indocyanine green angiography (ICGA), obtained simultaneously using the Heidelberg retina angiograph 2 (HRA2), were analyzed. LCs were associated with a relatively large extent (≥3000 μm) of peripapillary choroidal atrophy and a dark rim, the proliferation of retinal pigment epithelial cells surrounding the neovascular membrane was accompanied by a small extent. Myopic CNV usually developed in the LC area surrounded by tiny crack fragments. In all, 35 patients with LCs received FA and ICGA at least twice during follow-up. LC progression was observed in nine (25.7%) treated eyes and six (23.1%) non-CNV fellow eyes. Crack fragments progressed in three distinct forms such as elongation, branching, or bridging pattern. Newly diagnosed myopic CNV was reported in 18 treated eyes and 3 fellow eyes. Progression of LCs and development of CNV occurred simultaneously in eight eyes. By multivariate Cox's regression, a statistically significant association was observed between recurrence of myopic CNV and the absence of a dark rim on ICGA. The HRA2 instrument affords detailed high-resolution images of FA and ICGA. Notably, recurrence of myopic CNV developed in areas surrounded by new small crack fragments and LCs are considered to be important in the development of myopic CNV.


A reliable septum exists between the lateral cord and medial and posterior cords in the costoclavicular region: Clinical and microanatomical considerations in brachial plexus anesthetic blockade.
The ultrasound-guided proximal infraclavicular costoclavicular block (PICB) appears popular but its results are inconsistent. We sought an accurate demonstration of septae formed between the brachial plexus cords. We performed in-plane, lateral-to-medial PICBs on 120 patients and recorded images. Once the most superficial lateral cord component was entered, a 0.4-0.6 mA current was applied to confirm needle placement; 5 ml of local anesthetic (LA) solution was then injected and its spread was observed and recorded. As the needle was advanced, the presence or absence of a hyperechoic linear structure was noted before the deeper compartment was reached, specifically looking for the possible displacement of such a septum. Upon initial scanning, a septum was observed in 67 of the 120 patients (46.2%). However, there was clear displacement of a linear septum between the lateral cord compartment and the medial and posterior cord compartments that prevented spread between the compartments in 94.16% of patients. Piercing the septum evoked motor responses from the medial or posterior cord. The same anatomical regions were studied microanatomically by analyzing cross-sections obtained with the same approach angle as the ultrasound probe. Intraplexus fascial septae that bundled the medial and posterior cords into one compartment and separated them from the lateral cord were demonstrated and confirmed microanatomically. This suggests the need for two separate injections (or two separate catheter placements for continuous peripheral nerve blockade) into the superficial and deep compartments to ensure LA spread around all three cords of the brachial plexus at this level.


Glatiramer acetate could be a hypothetical therapeutic agent for neuromyelitis optica.
Neuromyelitis optica (NMO) is characterized by concurrence of optic neuritis and transverse myelitis, which is typically associated with a spinal cord lesion extending three or more vertebral segments. NMO is an inflammatory, demyelinating central nervous system disorder, and although it has a relapsing course in more than 90% of patients, it differs from multiple sclerosis in that it is more severe, usually spares the brain, and is associated with a longitudinally extensive lesion on spinal cord magnetic resonance imaging (MRI). Furthermore, NMO is associated with a highly specific serum marker called anti-aquaporin-4 antibody, which is believed to have a central pathogenetic role in NMO. Treatment with B-cell specific monoclonal antibody (rituximab) and plasma exchanges appears to reduce the severity and frequency of attacks in NMO, and therefore, B-cell autoimmunity as well as a humoral mechanism may be involved in the pathogenesis of NMO. Glatiramer acetate (GA; also known as Copaxone, COP-1) is a synthetic copolymer of a pool of peptides composed of random sequences of four amino acids: glutamine, lysine, alanine, and tyrosine. GA-specific T-helper 1- (Th1) and 2-type (Th2) cells produce brain-derived neurotrophic factor (BDNF), which may affect neuronal survival and myelin repair. GA treatment also leads to sustained augmentation of BDNF, neurotrophin (NT)-3, and NT-4 expression in various brain regions as demonstrated by histological analysis of immunostained brain sections and BDNF elevation after GA treatment on both protein and mRNA levels. GA-Th2 activation may also have a neuroprotective role in the course of NMO. Furthermore, B cells from GA-treated mice suppress experimental autoimmune encephalomyelitis. The pathogenesis of NMO is largely unknown. However, there is some evidence that B-cell autoimmunity, activation of eosinophils, and B-cell activating factor play important roles, based on neurotrophic factors, neuroprotection, anti-inflammation, and B-cell modulation, GA is thus a hypothetic potential treatment agent for NMO.


An erythromycin-resistance gene from an erythromycin-producing strain of Arthrobacter sp.
A gene (ermA) coding for a presumed erythromycin-resistance (ErR) determinant from an Er-producing Arthrobacter sp. strain (NRRLB3381) was isolated from a gene bank in phage vector lambda 2001 by probing with a Streptomyces ErR gene. Strongly hybridizing fragments were subcloned and the appropriate segments sequenced. The ermA gene is 76 mol% G + C in content and specifies a protein of 340 aa with an Mr of 37454. S1 nuclease mapping and primer extension identified the putative promoter, which resembles the consensus sequence of Escherichia coli promoters particularly in the -10 region. A potential ribosome-binding site (RBS) (AGGAG) was also located. Unexpectedly, the majority of in vivo ermA transcripts detected were only 245 nt long, suggesting that expression of ErR may be regulated post-transcriptionally. Substantial homology is observed between the predicted aa sequences of the ermA-coded protein and the products of three other ErR determinants, from organisms that do not produce Er.


Dataset on the interview-based survey of Moscow bicycle infrastructure.
The data were collected using Computer Assisted Telephone Interview with a questionnaire set of closed-ended and open-ended questions. Respondents' phone numbers were randomly generated. The survey sample included 1000 adult citizens of Moscow - active and potential users of bicycles (in equal proportions) who take or can take regular rides to destinations up to 5 km away, as of August 2018. The sample was representative in terms of gender-age and geographical distribution characteristics of the population. The data table is supplemented with the original questionnaire. Survey results were put in the database containing respondents' metadata and their answers, either encoded or provided as a plain text (for open-ended questions). No other processing was applied to the data to maintain suitability for different analyses. The data can be used in further research of cities' public transport infrastructure to evaluate its performance and returns on investment, to formulate initial hypotheses, to draft a survey strategy and design, and to verify results, etc. The provided questionnaire is a ready-to-deploy instrument for custom surveys in the related areas of research.


Mechanisms of antiangiogenic-induced arterial hypertension.
Antiangiogenic therapy has emerged as an important concept in the treatment of solid tumors. Vascular endothelial growth factor (VEGF) represents an important therapeutic target, as it is the primary mediator of angiogenesis and is induced by multiple tumor-relevant stimuli. Arterial hypertension has been commonly reported in all clinical trials testing inhibitors of angiogenesis (especially inhibitors of VEGF/VEGFR-2 signalling), with incidence ranging from 11% to 43% in all studies. The mechanism of elevated blood pressure in patients treated with antiangiogenic agents is not fully understood, but it is probably multifactorial, involving endothelial dysfunction and capillary rarefaction. Recently, several studies have suggested that early blood pressure rise was associated with better antitumoral efficacy and improved prognosis, making this commonly observed effect a promising marker of efficacy.


Moderate aerobic exercise, but not dietary prebiotic fibre, attenuates losses to mechanical property integrity of tail tendons in a rat model of diet-induced obesity.
The purpose of this study was to investigate the alterations with obesity, and the effects of moderate aerobic exercise or prebiotic dietary-fibre supplementation on the mechanical and biochemical properties of the tail tendon in a rat model of high-fat/high-sucrose (HFS) diet-induced obesity. Thirty-two male Sprague-Dawley rats were randomized to chow (n = 8) or HFS (n = 24) diets. After 12-weeks, the HFS fed rats were further randomized into sedentary (HFS sedentary, n = 8), exercise (HFS + E, n = 8) or prebiotic fibre supplementation (HFS + F, n = 8) groups. After another 12-weeks, rats were sacrificed, and one tail tendon was isolated and tested. Stress-relaxation and stretch-to-failure tests were performed to determine mechanical properties (peak, steady-state, yield and failure stresses, Young's modulus, and yield and failure strains) of the tendons. The hydroxyproline content was also analyzed. The HFS sedentary and HFS + F groups had higher final body masses and fat percentages compared to the chow and HFS + E groups. Yield strain was reduced in the HFS sedentary rats compared to the chow rats. Peak and steady-state stresses, failure strain, Young's modulus, and hydroxyproline content were not different across groups. Although the HFS + E group showed higher failure stress, yield stress, and yield strain compared to the HFS sedentary group, HFS + F animals did not produce differences in the properties of the tail tendon compared to the HFS sedentary group. These results indicate that exposure to a HFS diet led to a reduction in the yield strain of the tail tendon and aerobic exercise, but not fibre supplementation, attenuated these diet-related alterations to tendon integrity.


Ischemic colitis in Kawasaki disease.
A case of Kawasaki disease with colonic involvement is reported. Features suggesting ischemic colitis were seen on radiography and at laparotomy. Nonresective approach coupled with aspirin therapy successfully treated the colonic lesion.


Performance assessment of an adaptive model-based feedback controller: comparison between atracurium, mivacurium, rocuronium and vecuronium.
The performance of an adaptive model-based controller for the administration of atracurium, mivacurium, rocuronium and vecuronium was compared in 159 adult surgical patients. The degree of neuromuscular block was set to 90% for atracurium, rocuronium and vecuronium and to 95% for mivacurium. Performance was assessed by calculating the median prediction error (bias), median absolute performance error (inaccuracy), divergence, wobble, the mean offset and the mean standard deviation from the setpoint. All indices of controller performance showed minimal deviation of the actual neuromuscular block from the setpoint. Although the controller appeared to be able to control rocuronium induced block at 90% and mivacurium induced block at 95% better than atracurium and vecuronium block at 90%, the differences in the controller performance between the four studied relaxants were small and have hardly any clinical significance. We conclude that a model-based adaptive controller is useful in the administration of atracurium, mivacurium, rocuronium or vecuronium.


Etiological analysis and epidemiological comparison among adult CAP and NHCAP patients in Okinawa, Japan.
Etiological epidemiology and diagnosis are important issues for CAP and NHCAP. Despite the availability of effective therapies, significant morbidity and mortality ensues. We retrospectively analyzed the etiology of 200 pneumonia patients at the University of the Ryukyus Hospital. Patients were categorized into CAP (n = 97) or NHCAP (n = 103), according to the Japanese Respiratory Society guidelines. Diagnoses were made using clinical tests including, Gram stain, bacterial culture, serum and urinary tests. Pathogens were detected in 71% of patients, and identified as the source of infection in 52% (104/200). The majority of patients suffered from Streptococcus pneumoniae (32/200), Haemophilus influenzae (22/200), and Moraxella catarrhalis (16/200). Gram stain guided pathogen-oriented therapy decisions for 38 of 96 patients with unknown pathogens. Atypical pathogens were only diagnosed in CAP patients (n = 5). Severity of pneumonia was related to male sex (p = 0.006), and preexisting conditions, such as chronic heart failure (p < 0.001) and COPD (p < 0.001). Risk factors associated with increased length of stay included chronic heart failure, chronic renal failure, other pulmonary diseases and diabetes. Mortality for NHCAP patients was associated with lung cancer and bronchiectasis. CAP patients were more frequently admitted during winter months, while NHCAP patients were admitted during all other seasons. Seasonal patterns for individual pathogens could not be determined. Gram staining remains useful to guiding diagnostics. Pathogens affecting CAP and NHCAP patients were not significantly different; as such, attention should be focused on the management of underlying conditions. Clinical outcomes were not affected by guideline discordant therapy.


Investigation into the Pathology of Idiopathic Systemic Amyloidosis in Four Captive Badgers (Meles meles).
Systemic idiopathic amyloidosis was described in four captive badgers (Meles meles). Two animals (B1 and B2) were not enrolled in any trial, while animals B3 and B4 took part in a vaccine efficacy study and had been challenged with Mycobacterium bovis. A full set of tissues was collected and processed routinely for histopathological, immunohistochemical and ultrastructural studies. Splenomegaly was found in three out of four animals. Histopathological evaluation revealed congophilic, permanganate-resistant systemic amyloid deposits in the tissues of all badgers. Animals B2 and B4 displayed a marked granulomatous response to amyloid within the spleen. Animals B1 and B2 also displayed clinicopathological findings suggestive of chronic kidney disease. Ultrastructural examination identified peculiar star-shaped arrays of amyloid. Immunohistochemical studies were unrewarding. Systemic amyloidosis should be considered among the differentials of wasting in captive badgers.


Intracellular pH during ischemia in skeletal muscle: relationship to membrane potential, extracellular pH, tissue lactic acid and ATP.
Intracellular pH (pHi) was measured with double-barrelled microelectrodes during 4 h of complete tourniquet ischemia in rabbit gastrocnemius muscle (group I). The pHi was related to extracellular pH (pHe), membrane potential (Em), tissue lactic acid (LA) and ATP. A fall in pHi from 7.00 +/- 0.03 to 6.60 +/- 0.05 occurred during 4 h of ischemia, with a slight pH-drop (0.07 pH units) during the initial hour and a more pronounced drop of 0.13 pH units during the last hour of ischemia. These changes were paralleled by a considerable decrease in pHe from 7.30 +/- 0.01 to 6.36 +/- 0.05 and a sixfold increase of tissue LA. The buffering capacity during the 4 h of ischemia was estimated to 81.9 +/- 5.6 mmol H+/l X pH. In parallel with the reduction in pHe, the resting membrane potential decreased from -90 mV and stabilised at around -60 mV after 2 h of ischemia. A less negative cell interior would favour H+ extrusion since the Em-EH+ gradient was unchanged at about -70 mV during the entire period of ischemia. This could contribute to muscle fiber buffering during ischemia. In another set of experiments (group II) the muscular glycogen reserve was reduced 20 min prior to a 4 h period of ischemia. Thereby an ischemic state was created where ATP levels decreased to 30% of initial, in contrast to the unaltered ATP content in group I.(ABSTRACT TRUNCATED AT 250 WORDS)


Macrophage balance fraction determines the degree of immunosuppression and metastatic ability of breast cancer.
Macrophages are important immune cells in the tumor microenvironment and can be divided into two polarized subtypes, M1 and M2. M1 type macrophages have anti-tumor effects, while M2 type macrophages have pro-tumor effect. Most of the current researches are limited to the effect of M1 or M2 macrophages on tumors, while ignoring the overall balance of macrophages. Our research suggests that the macrophage balance fraction (MBF) can more effectively and comprehensively reflect the balance of tumor associated macrophages. Using bioinformatics analysis and in vitro experiments, we found that MBF is also an effective indicator of the degree of immunosuppression and metastatic ability of breast cancer, and different MBF environment can impact the migration and invasion ability of breast cancer cells. Finally, we also found that the mechanism of MBF changes in breast cancer may be affected by breast cancer-derived exosomes. In summary, MBF was proposed and validated as a novel indicator of macrophage balance state. Using this indicator, we found that the balance of macrophages can affect the degree of immunosuppression and metastatic ability of breast cancer.


Improving Physical Abuse Documentation and Photography through a Remote Peer Review Intervention.
Child Abuse Pediatrics is a small and geographically dispersed specialty. This article reports on an intervention to improve written and photodocumentation quality and uniformity in suspected child physical abuse cases, using a remote, de-identified case review system. In each cycle, participants submitted de-identified medical reports and photographs for review by a child abuse pediatrics expert. Experts evaluated 3 cycles of 5 cases using a novel rubric and assigned quality interventions for the participants based on their scores. 15 of 16 participants improved scores between cycles 1 and 3 (78% versus 89%, P < 0.001). All participants rated the program as helpful and would recommend it to a colleague. A quality improvement project administered via the internet improves the quality and uniformity of written and photographic documentation in child physical abuse evaluations.


Silver nanoparticles as a therapeutic agent in experimental cyclosporiasis.
Cyclosporiasis is an emerging worldwide infection caused by an obligate intracellular protozoan parasite, Cyclospora cayetanensis. In immunocompetent patients, it is mainly manifested by self-limited diarrhea, which is persistent and may be fatal in immunocompromised patients. The standard treatment for cyclosporiasis is a combination of two antibiotics, trimethoprim and sulfamethoxazole. Gastrointestinal, haematologic and renal side effects were reported with this combination. Moreover, sulfa allergy, foetal anomalies and recurrence were recorded with no alternative drug treatment option. In this study, silver nanoparticles were chemically synthesized to be evaluated for the first time for their anti-cyclospora effects in both immunocompetent and immunosuppressed experimental mice in comparison to the standard treatment. The effect of silver nanoparticles was assessed through studying stool oocyst load, oocyst viability, ultrastructural changes in oocysts, and estimation of serum gamma interferon. Toxic effect of the therapeutic agents was evaluated by measuring liver enzymes, urea and creatinine in mouse sera. Results showed that silver nanoparticles had promising anti-cyclospora potentials. The animals that received these nanoparticles showed a statistically significant decrease in the oocyst burden and number of viable oocysts in stool and a statistically significant increase in serum gamma interferon in comparison to the corresponding group receiving the standard treatment and to the infected non-treated control group. Scanning electron microscopic examination revealed mutilated oocysts with irregularities, poring and perforations. Biochemical results showed no evidence of toxicity of silver nanoparticles, as the sera of the mice showed a statistically non-significant decrease in liver enzymes in immunocompetent subgroups, and a statistically significant decrease in immunosuppressed subgroups. Furthermore, a statistically non-significant decrease in urea and creatinine was recorded in all subgroups. Thus, silver nanoparticles proved their effectiveness against Cyclospora infection, and this will draw the attention to its use as an alternative to the standard therapy.


Cigarette smoke induces epithelial-to-mesenchymal transition, stemness, and metastasis in lung adenocarcinoma cells via upregulated RUNX-2/galectin-3 pathway.
An elevated level of galectin-3, a carbohydrate-binding lectin implicated in tumorigenesis, metastasis, and epithelial-mesenchymal transition (EMT), has been found in cigarette smokers. However, the regulation of its expression and role in the pathogenesis of CS-induced EMT and lung cancer metastasis is unclear. Here, we have investigated the mechanism of CS-induced and galectin-3-mediated EMT in airway epithelial cells (AECs). A549 adenocarcinoma cells and primary small airway epithelial cells cultured on an air-liquid interface (ALI) were exposed to cigarette smoke extract (CSE), and MTT, trypan blue, migration, invasion, tumor spheroid and colony formation assays were performed to assess EMT phenotype. Immunoblotting was performed to assess EMT and stemness markers and other regulatory proteins. CSE exposure affected cell survival and morphology, migration, invasion, and clonogenicity of AECs, which were concomitant with an increase in the expression of EMT markers, galectin-3, and runt-related transcription factor-2 (RUNX-2), an osteogenic transcription factor and upstream regulator of galectin-3. Chemical inhibition or silencing of RUNX-2 downregulated galectin-3 and modulated EMT marker expression, migration, invasion, and clonogenicity in CSE-exposed AECs. Recombinant human galectin-3 also induced EMT and stemness-associated changes in the AECs, and GB1107, a galectin-3 inhibitor, ameliorated these changes. Further, CSE-induced intracellular ROS enabled an increase in RUNX-2 and galectin-3 expression, which were reversed by n-acetyl-cysteine. These results provide a novel mechanistic insight into CSE-induced EMT via RUNX-2/galectin-3 axis mediated through ROS, which promoted EMT-associated changes, including invasion, migration, and stemness in AECs, which could be implicated in CS-induced lung cancer progression.


The contribution of N-terminal truncated cMyBPC to in vivo cardiac function.
Cardiac myosin binding protein C (cMyBPC) is an 11-domain sarcomeric protein (C0-C10) integral to cardiac muscle regulation. In vitro studies have demonstrated potential functional roles for regions beyond the N-terminus. However, the in vivo contributions of these domains are mostly unknown. Therefore, we examined the in vivo consequences of expression of N-terminal truncated cMyBPC (C3C10). Neonatal cMyBPC-/- mice were injected with AAV9-full length (FL), C3C10 cMyBPC, or saline, and echocardiography was performed 6 wk after injection. We then isolated skinned myocardium from virus-treated hearts and performed mechanical experiments. Our results show that expression of C3C10 cMyBPC in cMyBPC-/- mice resulted in a 28% increase in systolic ejection fraction compared to saline-injected cMyBPC-/- mice and a 25% decrease in left ventricle mass-to-body weight ratio. However, unlike expression of FL cMyBPC, there was no prolongation of ejection time compared to saline-injected mice. In vitro mechanical experiments demonstrated that functional improvements in cMyBPC-/- mice expressing C3C10 were primarily due to a 35% reduction in the rate of cross-bridge recruitment at submaximal Ca2+ concentrations when compared to hearts from saline-injected cMyBPC-/- mice. However, unlike the expression of FL cMyBPC, there was no change in the rate of cross-bridge detachment when compared to saline-injected mice. Our data demonstrate that regions of cMyBPC beyond the N-terminus are important for in vivo cardiac function, and have divergent effects on cross-bridge behavior. Elucidating the molecular mechanisms of cMyBPC region-specific function could allow for development of targeted approaches to manipulate specific aspects of cardiac contractile function.


Differential risk factors for lacunar stroke depending on the MRI (white and red) subtypes of microangiopathy.
Leukoaraiosis and cerebral microbleeds (CMB), which represent cerebral microangiopathy, commonly coexist in patients with acute lacunar stroke. Since they may have different impacts on stroke prognosis and treatment, it is important to know the factors associated with leukoaraiosis-predominant vs. CMB-predominant microangiopathies. We prospectively recruited 226 patients with acute lacunar infarction and divided them into four groups according to the Fazekas' score and the presence of CMB: mild, red (predominant CMB), white (predominant leukoaraiosis) and severe microangiopathy groups. For comparison, we also evaluated 50 patients with intracerebral hemorrhage (ICH). We evaluated the clinical and laboratory findings of microangiopathy subtypes in patients with acute lacunar stroke and then compared them with those of primary ICH. The risk factor profile was different among the groups. Patients with acute lacunar infarct but mild microangiopathy were younger, predominantly male, less hypertensive, and more frequently had smoking and heavy alcohol habits than other groups. The risk factor profile of red microangiopathy was similar to that of ICH but differed from that of white microangiopathy. The subjects in the white microangiopathy group were older and more frequently had diabetes than those in the red microangiopathy or ICH group. After adjustments for other factors, age [odds ratio (OR) 1.13; 95% confidence interval (CI) 1.08-1.18; p<0.001] and diabetes (OR 2.28; 95% CI 1.02-5.13; p = 0.045) were independently associated with white microangiopathy, and age (OR 1.05; 95% CI 1.01-1.08; p = 0.010) was independent predictor for red microangiopathy compared to mild microangiopathy. Patients with acute lacunar infarction have a different risk factor profile depending on microangiopathic findings. Our results indicate that diabetes may be an one of determinants of white (leukoaraiosis-predominant) microangiopathy, whereas smoking and alcohol habits in relatively young people may be a determinants of mild microangiopahic changes in patients with lacunar infarction.


The importance of obtaining ankle-brachial indexes in older adults: the other vital sign.
As the aging population increases, so does the need to identify specific health problems associated with that age group and to develop and implement strategies to manage those problems efficiently. Peripheral arterial disease, a known threat to older adults' health and independence, often leads to decreased functional ability and potential limb loss. Nurses are in a unique position to screen older adults for the disease and to implement strategies to manage the problem. An overview of arterial physiology will be presented along with identification of risk factors, how to obtain ankle-brachial indexes and interpret the results, and treatment options for mild, moderate, and severe disease. Identifying the disease in its early stages and minimizing the effects will help keep older adults living independently and improve their quality of life.


Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants.
Drug eluting coatings that can direct the host tissue response to implanted medical devices have the potential to ameliorate both the medical and financial burden of complications from implantation. However, because many drugs useful in this arena are biologic in nature, a paucity of delivery strategies for biologics, including growth factors, currently limits the control that can be exerted on the implantation environment. Layer-by-Layer (LbL) polyelectrolyte multilayer films are highly attractive as ultrathin biologic reservoirs, due to the capability to conformally coat difficult geometries, the use of aqueous processing likely to preserve fragile protein function, and the tunability of incorporation and release profiles. Herein, we describe the first LbL films capable of microgram-scale release of the biologic Bone Morphogenetic Protein 2 (BMP-2), which is capable of directing the host tissue response to create bone from native progenitor cells. Ten micrograms of BMP-2 are released over a period of two weeks in vitro; less than 1% is released in the first 3 h (compared with commercial collagen matrices which can release up to 60% of BMP-2, too quickly to induce differentiation). BMP-2 released from LbL films retains its ability to induce bone differentiation in MC3T3 E1S4 pre-osteoblasts, as measured by induction of alkaline phosphatase and stains for calcium (via Alizarin Red) and calcium matrix (via Von Kossa). In vivo, BMP-2 film coated scaffolds were compared with film coated scaffolds lacking BMP-2. BMP-2 coatings implanted intramuscularly were able to initiate host progenitor cells to differentiate into bone, which matured and expanded from four to 9 weeks as measured by MicroCT and histology. Such LbL films represent new steps towards controlling and tuning host response to implanted medical devices, which may ultimately increase the success of implanted devices, provide alternative new approaches toward bone wound healing, and lay the foundation for development of a multi-therapeutic release coating.


Structural and elemental characterization of glass and ceramic particles for bone surgery.
Clinically used bioceramics have been characterized previously with different kinds of methods and comparison of results have proven to be difficult due to varieties of the material properties of interest. Therefore, in this study we compared clinically commonly used bioceramics of hydroxyapatite and carbonate apatite, two bioactive glasses 45S5 and S53P4, and alumina with respect of properties which according to the present knowledge are significant for bone biology. Physicochemical properties of the materials were characterized by various methods. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) was used to analyze the material vibrational features. X-ray Power Diffraction (XRD) was used to characterize the material crystal structure and scanning electron microscopy-energy-dispersive x-ray analysis (SEM-EDXA) was used to evaluate the morphology and size of the materials and to calculate their oxide content. The dissolution behavior of the materials, ion release and pH changes in Tris buffer in a continuous flow-through reaction for 24-hours were determined. The change of the surface of the bioactive glasses by interfacial reaction during the Tris immersion was examined and the thickness of the surface reaction layer of the materials was studied. SEM examination showed that the particle morphology of BG 45S5, BG S53P4 and alumina particle's surface was smooth. The surface of HAP was porous, but also CAP showed some surface porosity. An increase in the pH of the immersion solution was observed especially for BG 45S5 and BG S53P4. HAP, CAP and alumina caused only a minor increase in pH. BGs 45S5 and S53P4 showed a rapid initial release of sodium and calcium ions, followed by the release of silicon species. Minor release of sodium ions was registered for HAP, CAP and alumina. Calcium ion release was low but constant over the experimental time while only a minor initial dissolution was measured for HAP. The in vitro study showed differences in the materials' properties, which are considered to be important for biological suitability and in clinical applications, such as materials tomography, ion release and pH changes.


Composition-based methods to identify horizontal gene transfer.
The detection of horizontal gene transfer (HGT) events has become an increasingly important issue in recent years. Here we discuss a simple theoretical analysis based on the in silico artificial addition of known foreign genes from different prokaryotic groups into the genome of Escherichia coli K12 MG1655. Using this dataset as a control, we have tested the efficiency of four methodologies commonly employed to detect HGT, which are based on (a) the codon adaptation index, codon usage, and GC percentage (CAI/GC); (b) the distributional profile (DP) approach with a gene search in the closely related phylogenetic genomes; (c) the Bayesian model (BM); and (d) the first-order Markov model (MM). All methods exhibit limitations as shown here, with BM and MM giving better approximations. The MM has a better detection rate when genes from closely related organisms are evaluated. The application of the MM to detect recently transferred genes in the genomes of E. coli strain K12 MG1655 shows that this organism has undergone a rather significant amount of HGT, several of which have well-defined functions that appear to be involved in the direct interaction of the organisms with their environment.


The primary structure of human H-protein of the glycine cleavage system deduced by cDNA cloning.
A full-length cDNA encoding the human H-protein of the glycine cleavage system has been isolated from a lambda gt11 human fetal liver cDNA library. The cDNA insert was 1091 base pairs with an open reading frame of 519 base pairs which encoded a 125-amino acid mature human H-protein with a 48-amino acid presequence. Human H-protein is 97%, 86%, and 46% identical to the bovine, chicken, and pea H-protein, respectively.


Association of Metformin With Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.
Metformin is widely used among women with polycystic ovary syndrome (PCOS). However, its associations with outcomes of in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in women with PCOS remain controversial. To assess whether metformin is associated with improved outcomes of IVF/ICSI-ET in women with PCOS. PubMed, Embase, and Cochrane were searched from database inception to January 31, 2020. Only randomized clinical trials (RCTs) were included. Eligible studies enrolled women with PCOS undergoing infertility treatment with IVF/ICSI-ET and reported at least 1 outcome of IVF/ICSI-ET. This study followed the Preferred Reporting Items for Systematic Reviews and Meta analyses guidelines. Two authors independently extracted the data. Study quality was evaluated using the GRADE system. Treatment effect was quantified using odds ratios (ORs) with 95% CIs using random-effect models with the Mantel-Haenszel method. Ovarian hyperstimulation syndrome (OHSS), clinical pregnancy rate, and live birth rate. A total of 12 RCTs, which collectively included 1123 women with PCOS undergoing infertility treatment with IVF/ICSI-ET, were identified. The risk of OHSS in women randomized to metformin was lower than in women not randomized to metformin (OR, 0.43; 95% CI, 0.24-0.78), although this difference was not significant for women with PCOS with a body mass index of less than 26 (OR, 0.67; 95% CI, 0.30-1.51). There was no significant difference in clinical pregnancy rate (OR, 1.24; 95% CI, 0.82-1.86) or live birth rate (OR, 1.23; 95% CI, 0.74-2.04) in the total population studied. However, in a post hoc analysis among women with a body mass index of 26 or greater, metformin treatment was associated with increased clinical pregnancy rates (OR, 1.71; 95% CI, 1.12-2.60). In this study, metformin treatment was associated with a decreased risk of OHSS but had no association with the overall clinical pregnancy rate or live birth rate among women with PCOS undergoing IVF/ICSI-ET. Metformin treatment should be carefully considered for women with PCOS undergoing IVF/ICSI-ET and may be more preferred for women with a body mass index greater than 26.


Prostaglandin-E2 released by pre-implantation human conceptuses.
This work investigates the production of prostaglandin E2 (PGE2), a well known modulator for the suppression of immune cells, by pre-implantation human conceptuses from the 4-cell stage to the hatched blastocyst and by cumulus oophorus cells, these being obtained from an IVF/ET program. Cumulus cell complexes cultured for 48 h produced considerable amounts of PGE2, necessitating complete removal of their influence on the conceptus cultures. All stages of the human conceptus studied produced PGE2 during 48-h cultures, the greatest amounts from late blastocysts, and from those cultured in media containing bovine serum albumin rather than human donor serum. Indomethacin-treated control blastocysts confirmed the synthesis and release from the human conceptuses. The production of PGF2a from human blastocysts could not be demonstrated.


Integration of ethical considerations into HTA reports: an analysis of integration levels using a systematic review.
To describe the type and level of ethical integration in published health technology assessment (HTA) reports and systematically identify the ethical approaches utilized. A literature search was conducted with the Google™ search engine using the keyword "ethic" between 1 January 2015 and 20 August 2019. Only HTA assessment reports with a section on ethics were retained and classified according to their level of ethical integration: no ethical analysis, ethical issues highlighted, assessments according to legal or social norms, and assessments from a moral or axiological perspective-using a qualitative methodology to distinguish such integration. This review yielded 188 reports with a section identified as being on ethics, produced by seventeen HTA agencies in eleven countries. One hundred and thirty-six reports did not develop an ethical analysis, thirty-one highlighted ethical issues, seventeen conducted a norm-based ethical assessment using a descriptive approach grounded in social norms, and four developed an assessment grounded in a moral or axiological perspective. The bioethical "four-principles" framework was used, but mainly for presenting ethical issues and not as a moral framework. The majority of reports featuring a section on ethics mention ethical considerations without ethical analysis. Ethical issues are grouped with legal, social, and organizational issues and treated as contextual considerations that decision makers should be aware of. When reports present systematic norm-based ethical assessments from a descriptive perspective or ethical assessment based on a moral or axiological perspective, there is a tendency to ground these analyses in frameworks created for the purpose and reliant on a concept of ethics supporting them.


How robust are protein folding simulations with respect to force field parameterization?
Molecular dynamics simulations hold the promise of providing an atomic-level description of protein folding that cannot easily be obtained from experiments. Here, we examine the extent to which the molecular mechanics force field used in such simulations might influence the observed folding pathways. To that end, we performed equilibrium simulations of a fast-folding variant of the villin headpiece using four different force fields. In each simulation, we observed a large number of transitions between the unfolded and folded states, and in all four cases, both the rate of folding and the structure of the native state were in good agreement with experiments. We found, however, that the folding mechanism and the properties of the unfolded state depend substantially on the choice of force field. We thus conclude that although it is important to match a single, experimentally determined structure and folding rate, this does not ensure that a given simulation will provide a unique and correct description of the full free-energy surface and the mechanism of folding.


Transmission of hepatitis C virus during myocardial perfusion imaging in an outpatient clinic.
Reports of health care--associated viral hepatitis transmission have been increasing in the United States. Transmission due to poor infection control practices during myocardial perfusion imaging (MPI) has not previously been reported. The aim of this study was to identify the source of incident hepatitis C virus (HCV) infection in a patient without identified risk factors who had undergone MPI 6 weeks before diagnosis. Practices at the cardiology clinic and nuclear pharmacy were evaluated, and HCV testing was performed in patients with shared potential exposures. Clinical and epidemiologic information was obtained for patients with HCV infection, and molecular testing was performed to assess viral relatedness. Evidence of HCV transmission among patients who had undergone MPI at the cardiology clinic on 2 separate dates was found, involving 2 potential source patients and a total of 5 newly infected patients. Molecular testing identified a high degree of genetic homology among viruses from patients with common procedure dates. The nuclear medicine technologist routinely drew up flush from multidose vials of saline solution using the same needle and syringe that had been used to administer radiopharmaceutical doses. Multipatient use of vials was not observed, but a review of purchasing invoices and interviews with staff members suggested that this had occurred. No evidence of transmission via contamination of radiopharmaceuticals at the nuclear pharmacy was found. In conclusion, transmission of HCV occurred because of unsafe injection practices during MPI. Cardiologists should carefully review their infection control practices and the practices of other staff members involved with these procedures.


Medical ethics contributes to clinical management: teaching medical students to engage patients as moral agents.
In order to teach medical students to engage more fully with patients, we offer ethics education as a tool to assist in the management of patient health issues. We propose that many dilemmas in clinical medicine would benefit by having the doctor embark on an iterative reasoning process with the patient. Such a process acknowledges and engages the patient as a moral agent. We recommend employing Kant's ethic of respect and a more inclusive definition of patient autonomy drawn from philosophy and clinical medicine, rather than simply presenting dichotomous choices to patients, which represents a common, but often suboptimal, means of approaching both medical and moral concerns. We describe how more nuanced teaching about the ethics of the doctor-patient relationship might fit into the medical curriculum and offer practical suggestions for implementing a more respectful, morally engaged relationship with patients that should assist them to achieve meaningful health goals.


GSDME-Dependent Incomplete Pyroptosis Permits Selective IL-1α Release under Caspase-1 Inhibition.
Pyroptosis is a form of regulated cell death that is characterized by gasdermin processing and increased membrane permeability. Caspase-1 and caspase-11 have been considered to be essential for gasdermin D processing associated with inflammasome activation. In the present study, we found that NLRP3 inflammasome activation induces delayed necrotic cell death via ASC in caspase-1/11-deficient macrophages. Furthermore, ASC-mediated caspase-8 activation and subsequent gasdermin E processing are necessary for caspase-1-independent necrotic cell death. We define this necrotic cell death as incomplete pyroptosis because IL-1β release, a key feature of pyroptosis, is absent, whereas IL-1α release is induced. Notably, unprocessed pro-IL-1β forms a molecular complex to be retained inside pyroptotic cells. Moreover, incomplete pyroptosis accompanied by IL-1α release is observed under the pharmacological inhibition of caspase-1 with VX765. These findings suggest that caspase-1 inhibition during NLRP3 inflammasome activation modulates forms of cell death and permits the release of IL-1α from dying cells.


Comparison of the effects of tenoxicam and mid-laser irradiation on chronic adjuvant arthritis in rats.
This controlled experimental study was designed to compare the effects of a well-known NSAID, tenoxicam, with mid-laser irradiation on the inflammatory component of adjuvant-induced arthritis (AIA). Four groups of animals, each consisting of 10 Wistar rats, were included in the study. The primary concern was not to investigate the antiinflammatory effects of tenoxicam, but to compare the previously proven effects of this drug with a physical therapy agent which might be considered to have fewer side effects and/or contraindications. The first group received only 0.1 ml of complete Freund's adjuvant (CFA) and served as the control for the other groups. The 2nd, 3rd and 4th groups, after having CFA injected into the plantar surfaces of their right paws, were treated with tenoxicam alone, mid-laser alone, or with a combination of the two, respectively. All 3 groups showed significantly reduced paw edema compared with the control group. Although the reduction in paw edema in the animals treated with tenoxicam or with tenoxicam+ mid-laser was more significant, mid-laser is proposed as an alternative therapy for symptomatic relief in certain conditions well known to limit the use of NSAIDs.


A comparison of plasma prostaglandin levels in term and preterm labour.
Peripheral plasma levels of 13,14-dihydro-15-keto-prostaglandin F (PGFM) were determined in women during pregnancy and in term and preterm labour. The PGFM concentrations at term were not significantly different from the levels between 26 and 34 weeks gestation. In both term and preterm labour there was a rise in PGFM levels with increasing cervical dilatation although the mean values tended to be lower during preterm labour. These findings may provide an explanation for the effectiveness of prostaglandin synthetase inhibitors in suppressing myometrial activity in preterm labour.


[The endotoxin from S-, R- and M-forms of enteropathogenic E. coli O 149: pyrogenicity, Shwartzman-phenomenon and hypersensitivity (author's transl)].
The authors are interested in elucidation of the role of endotoxin from S, R- and M-forms of E. coli O 149, and of the role of hypersensitivity in pathogenesis of Colibacillosis. It was shown in this experiment that all S, R- and M-form of E. coli O149 possess endotoxin with almost the same pyrogenicity in normal rabbits. The pyrogenicity increases enormously in the hypersensitized rabbit. There were also not observed differences between endotoxins extracted from S, R, M-mutnants. All 3 endotoxins evoke in normal rabbits the skin Shwartzman-Phenomenon, the S-endotoxin was there much stronger. This phenomenon increases in capacity in hypersensitized rabbits. Thus again, the role of hypersensitivity in Colibacillosis was proved to be important.


Accumulation profiles of persistent organochlorines in liver and fat tissues of various waterbird species from Greece.
Waterbirds are particularly subject to accumulation of persistent organic pollutants (POPs) that have been shown to constitute a major hazard for this group of birds. Liver and fat tissue from ten species belonging to the orders Ciconiformes (Ardeidae, Ciconiidae, Phoenicopteridae) and Pelicaniformes (Pelecanidae, Phalacrocoracidae) were used as bioindicators in order to assess environmental pollution by POPs (HCHs, DDTs, cyclodienes, PCBs) in Greek wetlands. To our knowledge, this is the first study on POPs in livers of water birds in Greece and Eastern Mediterranean area. The DDTs consisted mainly of p,p'-DDE with percentages over 60% in the great majority of the samples. The highest summation SigmaDDT concentrations were measured in the liver and subcutaneous fat of Phoenicopterus rubber and in Ardea purpurea liver (15565, 24706 and 10406 ng g(-1) wet weight, respectively). Low concentrations of cyclodienes (Cycls) and HCHs were detected occasionally and the contamination pattern of OCPs in most species of waterbirds followed the order summation SigmaDDTs> summation SigmaCycls> summation SigmaHCHs. Individual values of total PCBs reached the levels of 4468 and 3252 ng g(-1) wet weight, for Nycticorax nycticorax and Egretta garzetta samples respectively. Some of the recorded differences in organochlorine concentrations could be due to different causes of death, with a subsequent effect on body lipid levels. Organochlorine pesticides and PCBs residues were lower than those commonly associated with mortality and reduced reproductive success in most species. However, low level exposure to these contaminants may constitute one of the many stressors that in combination could adversely affect bird populations.


Sequence characterization of the adenovirus 31 fibre and comparison with serotypes of subgenera A to F.
The amino acid sequence of the adenovirus type 31 (subgenus A) fibre polypeptide was deduced from the nucleotide sequence of the fibre gene. The analysed peptide sequence showed an organization consistent with the structural domains described for other adenoviruses: an amino-terminal tail region, an intervening shaft region and a carboxy-terminal knob. The AV31 fibre shaft displayed 20 repeats of the 15-amino-acid segments in the shaft domain, which agreed with the reported length of the fibre. The predicted AV31 fibre polypeptide sequence was compared to fibre polypeptides of serotypes representing subgenera A to F. As expected, AV31 and AV12, both belonging to subgenus A, showed the highest overall homology (75.4%). When comparing the AV31 fibre to the fibre polypeptides of subgenera B to F, AV31 and AV41 (subgenus F) shared the highest overall homology (35.3%), followed by AV40 (34.8%). The lowest overall homology (20.3%) was found for the AV31 and Av3 fibres (subgenus B). From the data presented, it could be suggested that AV31 is more closely related to the enteric viruses of subgenus F than to the other adenoviruses analysed. Comparing the fibre polypeptides of 14 adenovirus serotypes, 10 conserved amino acid sequences were detected, 5 of which were in the knob region. Since the fibre knob interacts with the host cell during infection, these conserved amino acids might be important for virus attachment. The gastroenteritis-causing adenoviruses AV40 and AV41 shared 3 additional conserved amino acid residues with AV31 and AV12 in the knob region.


The Masquelet technique combined with the muscle flap for use in emergency management of acute Gustilo type III trauma of the lower limb with segmental bone loss:Case series.
Gustilo-Anderson type III traumas have been described as high-energy injuries with severe bone defects and extensive soft tissue damage, which remain a challenging entity, due to an inherent risk of infection, nonunion and even amputation. The emergency management of such severe trauma presents additional difficulties. Our study attempts to retrospectively evaluate the Masquelet technique combined with the muscle flap for the management of Gustilo type III trauma of the lower limb with segmental bone loss in emergencies and assess key points of success in this technique. From June 2014 to December 2017, 17 patients of Gustilo type IIIA/B/C trauma of lower limb with segmental bone loss, were recruited for our studies. All the cases experienced thorough debridement, stabilization of fracture and antibiotic-impregnated cement spacer insertion. When necessary, muscle flap surgeries were performed immediately. After wound healing, cement spacers were removed, and cancellous bone was filled to repair bone defects. Procedures were performed by two experienced orthopedic surgeons. Among the patients studied, retrograde translocations of the medial head of the gastrocnemius were performed in 5 cases, medial hemimuscular flaps of soleus in 3 cases, and medial head of the gastrocnemius combined with medial hemimuscular flaps of soleus in 4 cases. One patient developed a necrotic soleus flap and was treated with the cross-leg flap. Using a mean 28.2 months of follow-up, results were analyzed radiologically and clinically. Failures (include infection and nonunion) were not noted. And all the patients returned to full weight bearing without pain. According to the Paley fracture healing score, 15 patients showed excellent results and 2 patients displayed good results regarding bone outcomes. When considering functional outcomes, 14 patients exhibited excellent results and 3 patients displayed good results. The muscle flap is synergistic with the Masquelet technique in the emergency management of severe complex fractures. The combination of both techniques in emergency surgery demonstrates an alternative option for the treatment of acute Gustilo type III trauma of the lower limb with segmental bone loss, which can effectively prevent bone infection and amputation. We also demonstrate that firm fixation is key to the Masquelet technique.


Effects of climate change on ecosystem services and their components in southern hills and northern grasslands in China.
We investigated the potential impacts of climate change on ecosystem services and their components in two distinct ecosystems: the northern grasslands and southern hills in China. The effects of minimum, average, and maximum temperature, and precipitation at monthly, seasonal, and yearly scales on ecosystem services and their components were studied through stepwise multiple regression analysis. The results showed that in the northern grasslands, an increase in the total ecosystem services value (ESV) was mainly attributed to soil conservation, biodiversity, hydrological regulation, and aesthetic landscape. In the southern hills, an increase in total ESV in each region was mainly attributed to climate regulation, environmental purification, biodiversity, and aesthetic landscape. There were strong correlations between ESVs and fluctuations in temperature and precipitation. In the northern grasslands, temperature was the main driving factor of the values from 11 categories of ecosystem services in Anxi, Tumuji, and Xilingol. However, in West Ordos, precipitation negatively affected the change in ESVs. In the southern hills, ESVs were governed by both precipitation and temperature in Huaying. Precipitation variables were an important factor affecting the ESVs in Cili. There was a stronger correlation between temperature and the majority of ESVs in Danjiangkou, Chongyi, and Lechang than precipitation. This paper provides a basis for a better understanding of the impact of climate change on different ecosystem services, and helps to enhance ESV under climate warming.


Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson's disease: involvement of antioxidative enzymes induction.
The neuroprotective effects of carnosic acid (CA), a phenolic diterpene isolated from rosemary (Rosmarinus officinalis), have been widely investigated in recent years, however, its protection in in vivo still unclear. In this study, we investigated the behavioral activity and neuroprotective effects of CA in a rat model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA). Rats were treated with 20mg/kg body weight of CA for 3 weeks before 6-OHDA exposure. Results indicated that CA improved the locomotor activity and reduced the apomorphine-caused rotation in 6-OHDA-stimulated rats. Significant protection against lipid peroxidation and GSH reduction was observed in the 6-OHDA rats pretreated with CA. Pretreatment with CA increased the protein expression of γ-glutamate-cysteine ligase catalytic subunit, γ-glutamate-cysteine ligase modifier subunit, superoxide dismutase, and glutathione reductase compared with 6-OHDA-stimulated rats and SH-SY5Y cells. Immunoblots showed that the reduction of the Bcl-2/Bax ratio, the induction of caspase 3 cleavage, and the induction of poly(ADP-ribose) polymerase (PARP) cleavage by 6-OHDA was reversed in the presence of SB203580 (a p38 inhibitor) or SP600125 (a JNK inhibitor) in SH-SY5Y cells. Rats treated with CA reversed the 6-OHDA-mediated the activation of c-Jun NH2-terminal kinase and p38, the down-regulation of the Bcl-2/Bax ratio, the up-regulation of cleaved caspase 3/caspase 3 and cleaved PARP/PARP ratio, and the down-regulation of tyrosine hydroxylase protein. However, BAM7, an activator of Bax, attenuated the effect of CA on apoptosis in SH-SY5Y cells. These results suggest that CA protected against 6-OHDA-induced neurotoxicity is attributable to its anti-apoptotic and anti-oxidative action. The present findings may help to clarify the possible mechanisms of rosemary in the neuroprotection of PD.


1-(2-Chloro-phenyl)-6-fluoro-2-methyl-1H-indole-3-carbonitrile.
In the title compound, C(16)H(10)ClFN(2), the dihedral angle between the indole ring system and the benzyl ring is 80.91 (5)°. The crystal packing features C-H⋯Cl, C-H⋯F and C-H⋯π inter-actions.


Long-term geothermal warming reduced stocks of carbon but not nitrogen in a subarctic forest soil.
Global warming is accelerating the decomposition of soil organic matter (SOM). When predicting the net SOM dynamics in response to warming, there are considerable uncertainties owing to experimental limitations. Long-term in situ whole-profile soil warming studies are particularly rare. This study used a long-term, naturally occurring geothermal gradient in Yukon, Canada, to investigate the warming effects on SOM in a forest ecosystem. Soils were sampled along this thermosequence which exhibited warming of up to 7.7℃; samples were collected to a depth of 80 cm and analysed for soil organic carbon (SOC) and nitrogen (N) content, and estimates made of SOC stock and fractions. Potential litter decomposition rates as a function of soil temperature and depth were observed for a 1-year period using buried teabags and temperature loggers. The SOC in the topsoil (0-20 cm) and subsoil (20-80 cm) responded similar to warming. A negative relationship was found between soil temperature and whole-profile SOC stocks, with a total loss of 27% between the warmest and reference plots, and a relative loss of 3%℃-1 . SOC losses were restricted to the particulate organic matter (POM) and dissolved organic carbon (DOC) fractions with net whole-profile depletions. Losses in POM-C accounted for the largest share of the total SOC losses. In contrast to SOC, N was not lost from the soil as a result of warming, but was redistributed with a relatively large accumulation in the silt and clay fraction (+40%). This suggests an immobilization of N by microbes building up in mineral-associated organic matter. These results confirm that soil warming accelerates SOC turnover throughout the profile and C is lost in both the topsoil and subsoil. Since N stocks remained constant with warming, SOM stoichiometry changed considerably and this in turn could affect C cycling through changes in microbial metabolism.


Lung Injury Induces Alveolar Type 2 Cell Hypertrophy and Polyploidy with Implications for Repair and Regeneration.
Epithelial polyploidization after injury is a conserved phenomenon recently shown to improve barrier restoration during wound healing. Whether lung injury can induce alveolar epithelial polyploidy is not known. We show that bleomycin injury induces alveolar type 2 cell (AT2) hypertrophy and polyploidy. AT2 polyploidization is also seen in short term ex vivo cultures, where AT2-to-AT1 transdifferentiation is associated with substantial binucleation due to failed cytokinesis. Both hypertrophic and polyploid features of AT2 cells can be attenuated by inhibiting the integrated stress response using the small molecule ISRIB. These data suggest that AT2 hypertrophic growth and polyploidization may be a feature of alveolar epithelial injury. Because AT2 cells serve as facultative progenitors for the distal lung epithelium, a propensity for injury-induced binucleation has implications for AT2 self-renewal and regenerative potential upon reinjury, which may benefit from targeting the integrated stress response.


Formation of chimeric patterns and segregation of cells in varied combinations of thorax forming imaginai disks ofDrosophila melanogaster.
Genetically marked thoracic imaginal disks ofDrosophila melanogaster were partially dissociated and reaggregated. After metamorphosis, combinations of dorsal proand mesothoracic disks gave rise to mosaics, whereas no such mosaics were formed in combinations of dorsal meso- and metathoracic disks. Adventitious bristles are formed by the metathoracic disk, but these were never integrated in a common pattern with mesothoracic bristles.


Parietal alpha underlies slower cognitive responses during interference processing in adolescents.
Adolescence is a critical period when cognitive control is rapidly maturing across several core dimensions. Here, we evaluated how healthy adolescents (13-17 years of age, n = 44) versus young adults (18-25 years of age, n = 49) differ across a series of cognitive assessments with simultaneous electroencephalography (EEG) recordings. Cognitive tasks included selective attention, inhibitory control, working memory, as well as both non-emotional and emotional interference processing. We found that adolescents displayed significantly slower responses than young adults specifically on the interference processing tasks. Evaluation of EEG event-related spectral perturbations (ERSPs) on the interference tasks showed that adolescents consistently had greater event-related desynchronization in alpha/beta frequencies in parietal regions. Midline frontal theta activity was also greater in the flanker interference task in adolescents, suggesting greater cognitive effort. Parietal alpha activity predicted age-related speed differences during non-emotional flanker interference processing, and frontoparietal connectivity, specifically midfrontal theta - parietal alpha functional connectivity predicted speed effects during emotional interference. Overall, our neuro-cognitive results illustrate developing cognitive control in adolescents particularly for interference processing, predicted by differential alpha band activity and connectivity in parietal brain regions.


Strain improvement of thermotolerant Saccharomyces cerevisiae VS strain for better utilization of lignocellulosic substrates.
Pentose-utilizing yeast development by protoplast fusion and sequential mutations and ethanol fermentation using lignocellulosic substrate. Protoplasts of thermotolerant Saccharomyces cerevisiae and mesophilic, xylose-utilizing Candida shehatae were fused by electrofusion. The fusants were selected based on their growth at 42 degrees C and ability to utilize xylose. The selected best fusant was mutated sequentially and 3 mutant fusants obtained were tested for their stability. The mutant fusant CP11 was found to be stable and used for lignocellulosic fermentation. The Prosopis juliflora wood material was hydrolysed with 1% sulphuric acid initially for 18 h at room temperature and then for 20 min at 121 degrees C. The acid hydrolysate was separated and used for detoxification by ethyl acetate and overliming. The hard cellulosic fraction was hydrolysed with Aspergillus niger crude cellulase enzyme for 18 h at 50 degrees C. The substrate (15% w/v) yielded 84 g l(-1) sugars, representing 80% (w/w) hydrolysis of carbohydrate content present in the lignocellulosic material. The acid and enzyme hydrolysates were then equally mixed and used for fermentation with the developed fusant yeast (CP11). The fusant yeast gave an ethanol yield of 0.459 +/- 0.012 g g(-1), productivity of 0.67 +/- 0.015 g l(-1) h(-1) and fermentation efficiency of 90%. Protoplast fusion followed by sequential mutations method gave a stable and good performing fusant with maximum utilization of reducing sugars in the media. This new method could be applied to develop fusants for better biotechnological applications.


X-ray solution scattering studies of protein folding.
Protein folding is a reaction in which an extended polypeptide chain acquires maximal packing through formation of secondary and tertiary structures. Compactness and shape are, therefore, critical properties characterizing the process of protein folding. Because the stability of the native state is determined by the subtle free energy balance between the native and denatured states, the characterization of the denatured state is also essential to understand the conformational stability of the native state. We show that solution X-ray scattering is the best technique available today to address these problems. Although the structural resolution of the unfolded or compact denatured states elucidated from solution X-ray scattering is low, it provides a variety of information complementary to that obtained by NMR or X-ray crystallography.


Clinical Impact and Predictors of the Slow-Flow Phenomenon after Endovascular Treatment of Infrapopliteal Lesions Using the Crosser Catheter in Patients with Critical Limb Ischemia.
To determine the clinical impact and predictors of slow flow after endovascular treatment (EVT) using the Crosser catheter for debulking infrapopliteal lesions associated with critical limb ischemia. This retrospective study included 65 patients with critical limb ischemia (70 limbs, 90 infrapopliteal lesions), who underwent EVT using the Crosser catheter between November 2011 and February 2017. The Crosser catheter was used when the balloon catheter could not be passed through the lesion or could not be dilated sufficiently. Slow flow was evaluated after atherectomy using Crosser and was defined as delayed antegrade flow to the foot (total number of cine frames >35). Following atherectomy, slow flow developed in 37 infrapopliteal lesions (41.1%). Despite secondary treatment, slow flow persisted in 29 of 37 lesions (78%). After atherectomy using the Crosser catheter, the balloon could be passed through the lesion in all cases. The wound healing rate at 1 year after EVT (overall, 67.8%) was significantly poorer in the presence of slow flow (rate with vs. without slow flow, 45.3% vs. 84.4%, respectively; P = .006), especially among patients with stage ≥3 baseline wound, ischemia, and foot infection. The active length of the Crosser catheter was a predictor of slow flow (odds ratio, 1.05; 95% confidence interval, 1.03-1.08; P < .001), with an optimal cutoff of 100 mm. Slow flow is associated with a poorer wound healing rate at 1 year, especially for patients with severe baseline ischemia. To reduce the risk of slow flow, the active length of the Crosser catheter should be kept at <100 mm.


Plant-derived nanotherapeutic systems to counter the overgrowing threat of resistant microbes and biofilms.
Since antiquity, the survival of human civilization has always been threatened by the microbial infections. An alarming surge in the resistant microbial strains against the conventional drugs is quite evident in the preceding years. Furthermore, failure of currently available regimens of antibiotics has been highlighted by the emerging threat of biofilms in the community and hospital settings. Biofilms are complex dynamic composites rich in extracellular polysaccharides and DNA, supporting plethora of symbiotic microbial life forms, that can grow on both living and non-living surfaces. These enforced structures are impervious to the drugs and lead to spread of recurrent and non-treatable infections. There is a strong realization among the scientists and healthcare providers to work out alternative strategies to combat the issue of drug resistance and biofilms. Plants are a traditional but rich source of effective antimicrobials with wider spectrum due to presence of multiple constituents in perfect synergy. Other than the biocompatibility and the safety profile, these phytochemicals have been repeatedly proven to overcome the non-responsiveness of resistant microbes and films via multiple pathways such as blocking the efflux pumps, better penetration across the cell membranes or biofilms, and anti-adhesive properties. However, the unfavorable physicochemical attributes and stability issues of these phytochemicals have hampered their commercialization. These issues of the phytochemicals can be solved by designing suitably constructed nanoscaled structures. Nanosized systems can not only improve the physicochemical features of the encapsulated payloads but can also enhance their pharmacokinetic and therapeutic profile. This review encompasses why and how various types of phytochemicals and their nanosized preparations counter the microbial resistance and the biofouling. We believe that phytochemical in tandem with nanotechnological innovations can be employed to defeat the microbial resistance and biofilms. This review will help in better understanding of the challenges associated with developing such platforms and their future prospects.


Recurrence of glenohumeral instability in patients with isolated rotator cuff repair after a traumatic shoulder dislocation.
The primary objective of this study was to assess the incidence of recurrent glenohumeral instability in patients over 40 years with isolated rotator cuff (RC) repair for traumatic shoulder dislocation. The secondary objectives were to identify risk factors for glenohumeral recurrence after RC repair and to describe the causes and incidences of re-intervention. In this retrospective cohort study, data of consecutive patients at a single trauma center between January 2014 and July 2019 were reviewed, and 84 patients with a mean age of 57 (range: 40-75) years and follow-up duration of 3.9 (2-6) years were included. The inclusion criteria were as follows: first traumatic anterior shoulder dislocation, reparable RC tear, primary arthroscopic RC repair, no labral or bony Bankart lesion repair, and at least 2 years of follow-up. Patients less than 40 years of age were excluded. Shoulder instability recurrences and surgical reinterventions were reviewed with medical records. Statistical analysis was performed for qualitative variables using the Chi-squared test. Statistical significance was set at P ≤ 0.05. There was one patient with a redislocation episode (1.2%) at 2.5 years after surgery, who was surgically treated. Age, subscapular tears, bony Bankart injuries, humeral defects, and associated neurological injuries were not risk factors for recurrence in this study. Ten patients (11.9%) required reintervention. Nine patients (10.7%) re-tore their RCs. Recurrent glenohumeral instability in active patients over 40 years with isolated RC repair after traumatic shoulder dislocation was infrequent, despite the incidence of significant Hill-Sachs defects, anterior glenoid defects, bipolar bone defects, size of the RC injury, and tendon re-tears. The incidence of re-interventions was 11.9%, with symptomatic RC retear as the main cause.


Comprehension and awareness of symptoms in women with dyspepsia.
Overlapping symptoms of gastro-oesophageal reflux disease and dyspepsia are a problem for physicians and patients. This study explored comprehension of dyspepsia symptoms and associated medical terminology among women with symptoms of dyspepsia. The US women aged > or = 18 years with dyspepsia (defined by Rome II criteria) were recruited in two phases, via direct mail, the Internet, clinical investigators and/or gastroenterologists. In phase I, subjects took part in an hour-long telephonic interview comprising open-ended questions relating to symptom frequency/duration, triggers/patterns and severity. During phase II, subjects took part in a 45-min telephonic interview, which explored their understanding of dyspepsia symptoms and their predominant or most bothersome symptom. Subjects with 'pure' dyspepsia (without overlapping symptoms of gastro-oesophageal reflux disease or irritable bowel syndrome) were sought, but of 777 subjects screened, most were excluded because of gastrointestinal comorbidities (irritable bowel syndrome, gastro-oesophageal reflux disease). Only 85 (11%) subjects had 'pure' dyspepsia of whom 11 withdrew. Of the 74 subjects interviewed, 70% were unfamiliar with the term 'dyspepsia'. Subjects reported several symptoms, including bloating (65%), gas (50%), nausea (41%) and discomfort (36%). Most subjects could distinguish between symptom bothersomeness and severity, and between pain and discomfort. Terms such as 'satisfactory relief', 'central upper abdominal discomfort', 'early satiety' and 'postmeal fullness' were often misunderstood. Subjects with 'pure' dyspepsia are rare, because of comorbidities. Dyspepsia-related terminology is often misunderstood by subjects.


Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer.
The prognosis for patients with esophageal cancer is poor, even among those who undergo potentially curative esophagectomy. The neutrophil:lymphocyte ratio (NLR) is hypothesized to reflect the systemic inflammatory response created by a tumor and is possibly predictive of tumor aggressiveness and propensity for metastasis. We performed a single-center retrospective analysis of esophageal cancer patients who underwent attempted curative esophagectomy at Weill Cornell Medical Center between 1996 and 2009. We collected data on patient demographics, clinical characteristics, and receipt of neoadjuvant treatment. Preoperative blood tests were used to calculate NLR. Elevated NLR was defined a priori as ≥5.0. Logistic regression modeling was performed to analyze characteristics associated with elevated NLR. We conducted Kaplan-Meier analyses and Cox regression modeling to determine estimates and predictors of disease-free and overall survival. We identified a total of 295 patients who underwent esophagectomy. The median duration of follow-up was 31 months (interquartile range [IQR] 13-61). There were 56 patients (18.9%) who had elevated NLR preoperatively. Receipt of neoadjuvant therapy was independently associated with high NLR (odds ratio [OR] 2.14, 95% confidence interval [95% CI] 1.02-4.51). In multivariable analyses, elevated NLR was associated with significantly worse disease-free (hazard ratio [HR] 2.26, 95% CI 1.43-3.55) and overall survival (HR 2.31, 95% CI 1.53-3.50). Preoperative NLR is a potential prognostic marker for recurrence and death after esophagectomy. It is unclear whether NLR reflects the degree of inflammatory response to the primary tumor or other patient-specific or tumor characteristics that predispose to recurrence. Further investigation is warranted to clarify the mechanisms explaining the observed associations between elevated NLR and poor outcomes in esophageal cancer.


Pars plana vitrectomy for visually disturbing vitreous floaters in pseudophacic eyes.
The aim of this study was to evaluate the role of vitrectomy in patients with visually disturbing vitreous opacities. A retrospective analysis of the patient characteristics and the outcome of all pseudophacic eyes, which consecutively received in the decade 1996 to 2005 20 G pars plana vitrectomy for visually disturbing floaters, was carried out at the Mainz University Eye Clinic. Forty-one eyes of 32 patients (63 % university graduates, median age: 64 years) were included in the study. The mean axial length of the globe was 25.3 mm (range: 22.8 to 28.9 mm). Additional pathologies having influence on the vitreous condition were history of laser or cryo retinopexy (12 ×), buckle surgery (5 ×), complicated cataract surgery (16 ×) and Nd:YAG laser capsulotomy (4 ×). Vitreous floaters were considered to be the result of posterior vitreous detachment alone in 61 %, of asteroid hyalosis accompanied by posterior vitreous detachment in 17 %, and vitreous syneresis in 15 % of the eyes. Intraoperatively retinopexy with endolaser or cryo was performed in 6 % of cases. A secondary retinal detachment occurred in one eye (2 %). Thirty-one of 32 patients reported to be very satisfied with the postoperative result. Objectively, their visual acuity was better than or equal to preoperative acuity in 95 % of the eyes. Pars plana vitrectomy provides a highly effective treatment for visually disturbing vitreous floaters. In an era in which the expectations and demands of individuals on the quality of vision and life have increased significantly, with careful case selection the benefits of the surgical intervention may outweigh the surgical risks.


Does performance of robot-assisted laparoscopic radical prostatectomy within 2 weeks of prostate biopsy affect the outcome?
The aim of this study was to determine whether robot-assisted laparoscopic radical prostatectomy (RALP) performed within either 2 or 4 weeks of prostate biopsy is associated with surgical difficulty or immediate postoperative outcome. Of the 121 patients that underwent RALP at our institution, 104 patients were prospectively included. Patients were sequentially divided into three groups: first patient in group A (interval from biopsy to RALP: 2 weeks), second patient in group B (2-4 weeks), third patient in group C (more than 4 weeks), fourth patient in group A, and so on. The clinical, operative, pathological, and postoperative functional data were collected. Group A consisted of 31 patients, group B of 33, and group C of 40 patients. Median patient age and median follow up were 61.1 years and 14.1 months, respectively. In group A, mean estimated blood loss was significantly higher than the other two groups, even though there was no significant difference in the mean console time. Postoperative complications did not make any difference among the groups. In the multivariable analysis, the interval from biopsy to surgery did not affect operative times or surgical margins, or the immediate postoperative outcomes (e.g. recovery of erectile function, continence, and biochemical recurrence). A short interval for less than two weeks between the prostate biopsy and the RALP seems to be feasible and safe. Further studies with larger samples are needed to corroborate these findings.