Medicine as a corporate enterprise, patient welfare centered profession, or patient welfare centered professional enterprise?
There is an alarming trend in the field of medicine, whose portents are ominous but do not seem to shake the complacency and merry making doing the rounds.The wants of the medical man have multiplied beyond imagination. The cost of organizing conferences is no longer possible on delegate fees. The bottom-line is: Crores for a Conference Millions for a Mid-Term. However, the problem is that sponsors keep a discreet but careful tab on docs. All in all, costs of medicines escalate, and quality medical care becomes a luxury. The whole brunt of this movement is borne by the patient.Companies like GlaxoSmithKline, Bayer, Pfizer, Bristol-Myers Squibb, AstraZeneca, Schering-Plough, Abbott Labs, TAP Pharmaceuticals, Wyeth and Merck have paid millions of dollars each as compensation in the last few years. The financial condition of many pharmaceutical majors is not buoyant either. Price deflation, increased Rand D spending, and litigation costs are the main reasons. In the future, the messy lawsuits situation would no longer be restricted to industry. It would involve academia and practising doctors as well. Indian pharma industry captains, who were busy raking in the profits at present, would also come under the scanner. If nothing else, it means industry and docs will have to sit down and do some soul searching.Both short and long-term measures will have to be put into place. Short-term measures involve reduction in i) pharma spending over junkets and trinkets; ii) hype over 'me too' drugs; iii) manipulation of drug trials; iv) getting pliant researchers into drug trials; iv) manipulation of Journal Editors to publish positive findings about their drug trials and launches; v) and for Indian Pharma, to conduct their own unbiased clinical trial of the latest drug projected as a blockbuster in the West, before pumping in their millions.The long-term measures are related to the way biomedical advance is to be charted. We have to decide whether medicine is to become a corporate enterprise or remain a patient welfare centered profession. A third approach involves an eclectic resolution of the two. Such amount of patient welfare as also ensures profit, and such amount of profit as also ensures patient welfare is to be forwarded. For, profit, without patient welfare, is blind. And patient welfare, without profit, is lame. According to this approach, medicine becomes a patient welfare centered professional enterprise.The various ramifications of each of these approaches are discussed in this monograph.


[Bilateral testicular Leydig cell tumor. Procedure to follow].
The authors report one case of a bilateral testicular Leydig cell tumor in a man of 29 years old. There are few cases of such tumors reported in the literature. Gynecomastia force the patient to consult his doctor. His hormonal profile is practically normal; however, the serum estradiol is at the limit superior of normal range, and serum testosterone at the limit inferior. Testicular palpation is normal. It is the scrotal ultrasonography which confirms the diagnosis of testicular tumor. The scrotal ultrasonography has to be performed in every patient with unexplained gynecomastia. There is no metastasis. Before the treatment, the sperm conservation is performed (his sperm is normal). Our surgical sequence for this man without children was the next one: 1. inguinal orchiectomy was performed at the side of bigger tumor. Histological diagnosis was the benign Leydig cell tumor; 2. one month later, an inguinal orchidotomy at the other side was performed and the tumor palpable of 9 mm was removed. The extemporaneous biopsy confirmed the same diagnosis as at the other side; 3. one year later, there is no metastasis and the woman of our patient becomes pregnant.


Agency, reflexivity and risk: cosmopolitan, neurotic or prudential citizen?
The purpose of this paper is to critically examine the turn to risk within sociology and to survey the relationship between structure and agency as conceived by popular strands of risk theorizing. To this end, we appraise the risk society, culture of fear and governmentality perspectives and we consider the different imaginings of the citizen constructed by each of these approaches. The paper goes on to explore what each of these visions of citizenship implies for understandings of the structure/agency dynamic as it pertains to the question of reflexivity. In order to transcend uni-dimensional notions of citizenship and to reinvigorate sociological debates about risk, we call for conceptual analyses that are contextually rooted. Exampling the importance of knowledge contests around contemporary security threats and warnings of the deleterious effects of pre-emptive modes of regulation that derive from the 'risk turn' within social science, we argue for a more nuanced embrace of reflexivity within risk theorising in order to facilitate a more dynamic critique of the images of citizenship that such theorizing promotes.


The factor V-activating enzyme (RVV-V) from Russell's viper venom. Identification of isoproteins RVV-V alpha, -V beta, and -V gamma and their complete amino acid sequences.
The complete amino acid sequences of two isoproteins of the factor V-activating enzyme (RVV-V) isolated from Vipera russelli (Russell's viper) venom were determined by sequencing S-pyridylethylated derivatives of the proteins and their peptide fragments generated by either chemical (cyanogen bromide and 2-(2-nitrophenylsulfenyl)-3-methyl-3-bromoindolenine) or enzymatic (trypsin, alpha-chymotrypsin, and lysyl endopeptidase) cleavages. Both enzymes, designated RVV-V alpha and RVV-V gamma, consist of 236 amino acid residues and have a N-linked oligosaccharide chain at Asn229. The six amino acid substitutions between RVV-V alpha and -V gamma are: Thr22(alpha)-Ala22(gamma), Gly29(alpha)-Ala29(gamma), Gln191(alpha)-Glu191(gamma), Ile192(alpha)-Met192(gamma), Gln193(alpha)-His193(gamma), and Asn224(alpha)-Ser224(gamma). The molecular weights were calculated as 26,182 for RVV-V alpha and 26,167 for RVV-V gamma. The sequences of the RVV-V isoproteins exhibited 62% identity with that of batroxobin, a thrombin-like enzyme present in Bothrops atrox venom, and 33% identity with that of human thrombin B chain. The most interesting difference between the structures of RVV-V and other trypsin-type serine proteases is that the conservative Ser214-Trp215-Gly216 sequence (chymotrypsinogen numbering), considered as the site of antiparallel beta-sheet formation between the protein substrate and most serine proteases, has been replaced by the corresponding sequence Ala-Gly-Gly.


[A Biphasic Anaphylactic Attack from Sugammadex with a Severe Second Attack].
A 74-year-old man was scheduled for transurethral resection of the prostate under general anesthesia. Anesthesia was induced by propofol, rocuronium, remifentanil and maintained with sevoflurane. The operation was finished in 56 minutes without trouble. After operation, sugammadex was administered, and after about 2 minutes, redness, tachycardia, hypotension and itchiness appeared. Treatment was initiated using steroids, adrenaline, and antihistamine upon diagnosis of anaphylaxis caused by sugammadex. Reaction to the treatment was good and the general condition improved to normal; however, the patient was moved to the intensive care unit for follow-up observation. Furthermore, no upper respiratory tract symptoms were observed during the follow-up along with no decline in SpO2. The condition progressed without any particularly major abnormalities after entering the intensive care unit; however, a sudden decline in blood pressure and dyspnea occurred again 3 hours following entering the intensive care unit. These were considered to be biphasic reactions due to anaphylaxis, and treatment was carried out again with intravenous injection of adrenaline, steroids and inhalation of beta-agonist. No symptoms were observed since and the patient was discharged from the intensive care unit the following day.


Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-N-(2'-Phenylethyl)-Butyramide.
Quorum sensing (QS) antagonists have been proposed as novel therapeutic agents to combat bacterial infections. We previously reported that the secondary metabolite 3-methyl-N-(2'-phenylethyl)-butyramide, produced by a marine bacterium identified as Halobacillus salinus, inhibits QS controlled phenotypes in multiple Gram-negative reporter strains. Here we report that N-phenethyl hexanamide, a structurally-related compound produced by the marine bacterium Vibrio neptunius, similarly demonstrates QS inhibitory properties. To more fully explore structure-activity relationships within this new class of QS inhibitors, a panel of twenty analogs was synthesized and biologically evaluated. Several compounds were identified with increased attenuation of QS-regulated phenotypes, most notably N-(4-fluorophenyl)-3-phenylpropanamide against the marine pathogen Vibrio harveyi (IC50 = 1.1 µM). These findings support the opportunity to further develop substituted phenethylamides as QS inhibitors.


A re-examination of the vesicle hypothesis of transmission in relation to its applicability to the mammalian central nervous system.
The methods used to detect transmitters in the central nervous system, and their accuracy, are reviewed. The applicability of each of the seven different criteria used to define a transmitter is then examined, particularly in respect of substances not generally accepted as transmitters, but fulfilling some of these criteria. Twenty-three separate assumptions inherent in the vesicle hypothesis of transmission are identified; some of them are unproved and some unprovable. It is concluded that too many of these assumptions are in the latter two categories, which, from a Popperian viewpoint, render the hypothesis as a whole unwarrantable.


VaporSPOT: Parallel Synthesis of Oligosaccharides on Membranes.
Automated chemical synthesis has revolutionized synthetic access to biopolymers in terms of simplicity and speed. While automated oligosaccharide synthesis has become faster and more versatile, the parallel synthesis of oligosaccharides is not yet possible. Here, a chemical vapor glycosylation strategy (VaporSPOT) is described that enables the simultaneous synthesis of oligosaccharides on a cellulose membrane solid support. Different linkers allow for flexible and straightforward cleavage, purification, and characterization of the target oligosaccharides. This method is the basis for the development of parallel automated glycan synthesis platforms.


Human milk banking acceptability among pregnant and nursing mothers in Southwest Nigeria.
Human milk bank is a sustainable source of donor human milk (DHM) which is an acceptable alternative to the mother's milk and it is not routinely available in Nigeria, a multi-ethnically diverse country.The study aimed to assess the willingness to donate or accept human milk among pregnant women and mothers attending the antenatal, immunization, outpatient, under-five, and neonatal follow-up clinics in selected health facilities in Ekiti State, Southwest Nigeria. A descriptive cross-sectional, mixed methods study design was used to collect data in selected health facilities in Ekiti State. Questionnaires and focus group discussions were used to collect quantitative and qualitative data respectively while data analysis was done using the IBM® Statistical Package for Social Science SPSS version 26® and thematic analysis respectively. Of the 798 respondents, 529 (66.3%) and 626 (78.4%) did not know about wet nursing or human milk banking (HMB) respectively and 139 (17.4%) were willing to donate their breastmilk for a stipend. In the focus group discussion, 50% had heard about wet nursing but none heard about HMB. Maternal educational level had a significant impact on their willingness to donate or accept DHM (p < 0.00). Wholesomeness, cultural, and religious biases were major reasons affecting HMB acceptability. Awareness and perception of HMB are poor. Appropriate information, education, and counselling on HMB are needed to drive the adoption and establishment of HMB in Nigeria.


The relationship between papillary thyroid carcinoma and preoperative TSH level: A cross-sectional study from Syria.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and thyroid stimulating hormone (TSH) is the major growth factor for thyroid cells. It is also an available, inexpensive test and performed routinely while evaluating thyroid nodules. Yet the relationship between TSH levels and PTC is still controversial. Understanding the relationship between preoperative TSH levels and thyroid cancer helps to break new ground of current prevention, diagnosis, and management approaches of thyroid cancer. A cross-sectional retrospective study of patients underwent total thyroidectomy during 2019 at Al-Assad University Hospital, which included 305 individuals. All patients underwent thyroid ultrasonography and laboratory assessment of serum TSH levels prior to surgery, in addition to recording histological features of resected thyroid samples. The malignancy rate was 21.3%, PTC patients had higher TSH values across the entire study even when gender, age and number of thyroid nodules differed. A statistically significant increase in TSH levels was noticed by moving from the benign thyroid nodular disease (BTND) group to papillary thyroid microcarcinoma (PTMC) group, then to thyroid cancer of larger size (TCLS) group (P = .001). A statistically significant relationship was also found between high TSH levels and lymph node metastases (LNM) (P = .008). TSH concentrations were significantly higher in patients with PTC, and higher TSH values were associated with TCLS and LNM.


Sporulation of Clostridium cellulolyticum while grown in cellulose-batch and cellulose-fed continuous cultures on a mineral-salt based medium.
Clostridium cellulolyticum sporulation was investigated during growth on cellulose fibers in a mineral-salt based medium which corresponds to conditions linked to its natural ecological niche. At steady state of the continuous cultures under limitation and with an excess of cellulose and/or ammonium, bacterial cells mainly sporulated at low dilution rates (D), at least 10% sporulation being observed at the lowest D tested. Increasing the cellulose concentration in the feed-medium reservoir increased the percentage of spores in the bioreactor. It appeared that the remaining undigested cellulose could serve as an exogenous carbon source supply at a continuous but limited rate throughout the sporulation process. In addition to the proportion of carbon and nitrogen, the influence of the environmental pH on spore formation was studied. In cellulose-fed continuous cultures at a constant D and a pH decreasing from 7.2 to 6.4, the percentage of spores increased to 14% at the lowest pH tested. When C. cellulolyticum was grown in batch culture, the level of sporulation was dramatically higher in unregulated-pH fermentation compared to pH-controlled growth conditions at pH 7.2 since in the former it reached 45% within 5 days of cultivation. It then appeared that a low specific growth rate and a low environmental pH in the presence of an insoluble carbon substrate were the major factors inducing sporulation in C. cellulolyticum. Furthermore, since the spores adhere to the carbon substrate (the cellulose) the bacteria gain advantages when the environment allows germination thanks to the recovery of suitable growth conditions. By allowing the maintenance and the integrity of the bacteria in the microbiota, spore formation could then explain the successful survival of C. cellulolyticum in cellulosic anaerobic habitats where low environmental pH conditions are often found.


Vacuum-and-solvent-free fabrication of organic semiconductor layers for field-effect transistors.
We demonstrate that cold and hot isostatic pressing (CIP and HIP) is a novel, alternative method for organic semiconductor layer fabrication, where organic powder is compressed into a layer shape directly on a substrate with 200 MPa pressure. Spatial gaps between powder particles and the other particles, substrates, or electrodes are crushed after CIP and HIP, making it possible to operate organic field-effect transistors (OFETs) containing the compressed powder as the semiconductor. The CIP-compressed powder of 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT) had a hole mobility of (1.6 ± 0.4) × 10(-2) cm(2)/Vs. HIP of C8-BTBT powder increased the hole mobility to an amorphous silicon-like value (0.22 ± 0.07 cm(2)/Vs) because of the growth of the C8-BTBT crystallites and the improved continuity between the powder particles. The vacuum and solution processes are not involved in our CIP and HIP techniques, offering a possibility of manufacturing OFETs at low cost.


Bretylium tosylate--induced stabilization of electrical systole duration in patients with acute myocardial infarction.
The electrical systole duration (QTc), heart rate, and the QTc/QTt ratio were studied during the hospital course of an uncomplicated AMI in 13 patients treated with bretylium tosylate (10 mg/mg/24 hr over 5 days since confirmation of AMI) and in 19 controls. The QTc/QTt ratio showed prolongation of electrical systole duration in control subjects with a maximal value at the second day after AMI. QTc increased in these patients from day 1 to day 2 after AMI (402 +/- 4 msec vs. 430 +/- 3 msec, p less than 0.05) and decreased in the following days (p less than 0.05). During hospitalization cardiac rate was constant in both groups. In contrast, patients treated with bretylium tosylate showed a stable duration of QTc and the QTc/QTt ratio did not indicate prolongation of electrical systole duration. After drug discontinuation a slight increase in QTc duration was noticed (391 +/- 6 msec vs. 413 +/- 5 msec, p less than 0.05). These observations may contribute to the understanding of the antiarrhythmic action of bretylium and would indicate its usefullness in AMI patients with prolonged QTc and high risk of life-threatening arrhythmias.


Task-Specific Training for Adults With Chronic Knee Pain: A Case Series.
Study Design Case series. Background Recent evidence suggests that traditional impairment-based rehabilitation approaches for patients with knee pain may not result in improved function or reduced disability. This case series describes a novel task-specific training approach to exercise therapy for patients with chronic knee pain and reports changes in measures of clinical outcome (pain and physical function) following participation in the training program. Case Description Seven patients with chronic knee pain aged 40 years or older were included. Each reported at least "moderate" difficulty with sit-to-stand transfers, floor transfers, and/or stair negotiation at baseline. Experienced physical therapists provided between 8 and 16 treatment sessions focusing on improving performance of difficult or painful tasks. Outcomes A majority of patients demonstrated clinically important improvements in both patient-rated outcomes (Knee injury and Osteoarthritis Outcome Score, numeric pain-rating scale, modified Arthritis Self-Efficacy Scale) and performance-based outcomes (30-second chair-rise test, timed stair-climb test, floor transfer test, Performance Assessment of Self-Care Skills). Discussion A task-specific training approach for patients with chronic knee pain was described and yielded considerable improvement in pain and function for most of the individuals in this case series. Larger studies are needed to determine how task-specific training compares with more traditional impairment-based exercise approaches for chronic knee pain. Level of Evidence Therapy, level 5. J Orthop Sports Phys Ther 2017;47(8):548-556. doi:10.2519/jospt.2017.7349.


Growth pattern of intrauterine growth retarded (IUGR) babies in first nine months of life.
Forty-one full term intrauterine growth retarded (IUGR) babies of different maternal etiologies viz. maternal undernutrition (12), small maternal size (12), toxaemia of pregnancy (9) and idiopathic (8) were studied for growth pattern during first 9 months of life. Eighteen fullterm and 11 preterm who were appropriate for gestational age served as controls. These mothers were comparable for age, parity, socioeconomic status, weight and height (except in small size mothers), haemoglobin and plasma albumin (except in undernourished group). The various anthropometric parameters studied were weight, crown-heel length, head circumference, their velocities and ponderal index. The IUGR babies of undernourished mothers had lowest means for weight, crown-heel length and skull circumference. The babies of small sized mothers suffered most in crown-heel length followed by weight. The head growth was not affected in these babies. The IUGR babies of mothers with toxaemia of pregnancy demonstrated a catch up growth for all three parameters. The IUGR babies of idiopathic group showed a spurt in weight gain around 3 to 6 months and a similar spurt for crown heel length and head circumference was observed between 6 to 9 months of age. These babies were close to IUGR babies of mothers with toxaemia of pregnancy at 9 months. The preterm AGA babies also demonstrated a catch up growth for the weight, crown heel length and circumference.


Quality of life and characteristics of diabetic patients.
This study aimed to assess the association between quality of life and clinical and sociodemographic variables in type 2 diabetes patients, after they had started treatment in Primary and Specialized Health Care. This is an analytical cross-sectional study with a sampling of diabetic patients from Primary (n = 385) and Specialized (n = 385) Health Care. The dependent variable, quality of life, was evaluated by the Diabetes Quality of Life Measure - Brazil. Clinical and sociodemographic data were collected. Bivariate analysis by chi square test tested the association between the dependent variable with the independent ones. Next, we performed an analysis of multiple logistic regression. In Specialized Health Care, individuals who practice physical activity had less chance of having worse quality of life and those with less time of diagnosis presented higher chance of worse quality of life. In Primary Health Care, those who performed diets and presented glycated hemoglobin ≤ 7% had less chance of having worse quality of life. Women presented higher chances of worse quality of life than men. We concluded that with exception to the time of diagnosis and sex, other variables that influenced quality of life of diabetics were modifiable factors (glycated hemoglobin, alimentary diet and physical activity).


The shape language in application to the diagnosis of cervical vertebrae pathology.
In this paper the possibility of classification of X-ray images of the cervical vertebrae is studied. The images should be classified into one of the following classes-the images of healthy vertebrae and the images of vertebrae with syndesmophytes. The vertebra contours, described unambiguously by using the generalized shape language, are the basis of the analysis. As a result, the contour is represented as a chain of sinquads that determine switches. The found switches are the characteristic points of the analyzed contour. In these points additional features of the contour are determined. On the basis of these features two aforementioned classes of images are defined as fuzzy sets. Such an approach allows us to create a hierarchical algorithm of classification based on the syntactic and fuzzy description of the contour.


Facile Two-Step Synthesis of 1,10-Phenanthroline-Derived Polyaza[7]helicenes with High Fluorescence and CPL Efficiency.
A facile two-step synthesis of aza[7]helicenes possessing a 6-5-6-6-6-5-6 skeleton from commercially available 2,9-dichloro-1,10-phenanthroline via double amination with aniline derivatives followed by hypervalent iodine reagent-mediated intramolecular double-NH/CH couplings was developed. Single-crystal X-ray analyses of the helicenes revealed unique structures, including both a significantly twisted center and planar terminals of the skeleton. The azahelicenes show high fluorescent quantum yields (Φs) under both neutral (Φ: 0.25-0.55) and acidic conditions (Φ: up to 0.80). An enantiomerically pure aza[7]helicene showed high circularly polarized luminescence (CPL) activity under both neutral and acidic conditions (glum : up to 0.009).


Bevacizumab as a last-line treatment for glioblastoma following failure of radiotherapy, temozolomide and lomustine.
In previous trials, bevacizumab failed to prolong the overall survival time in newly diagnosed glioblastoma and at the first recurrence. Randomized clinical trials at the second or further recurrence following the failure of radiotherapy, temozolomide and lomustine, and retrospective analyses focusing on this specific cohort, are not yet available. A total of 62 patients with glioblastoma who received bevacizumab after the failure of standard care, including radiotherapy, temozolomide and lomustine, were retrospectively identified. Patient characteristics, previous treatment details, concomitant therapy, response based on the Response Assessment in Neuro-Oncology criteria, and progression-free survival (PFS) and overall survival (OS) times and rates were evaluated. Furthermore, the PFS and OS times and rates were analyzed for responders and non-responders. Of the patients, 54.8% (n=34) responded to treatment [complete response (CR) 3.2%, n=2; partial response (PR) 51.6%, n=32]. The median PFS time was 3.5 months and the median OS time was 7.5 months. The PFS rate at 6 months was 21.5% and the OS rate at 12 months was 11.5%. Responders (CR or PR) experienced a superior median PFS time compared with non-responders (i.e. stable or progressive disease; 5.4 vs. 1.9 months; P<0.0001) and a superior PFS rate at 6 months (34.9 vs. 7.1%; P<0.0001). The median OS time (8.6 vs. 6.4 months; P<0.0001) and OS rate at 12 months (21.3 vs. 0%; P<0.0001) were also superior in patients who exhibited a response to bevacizumab treatment. In conclusion, the objective response rate and the PFS and OS times and rates indicate that bevacizumab has activity in patients with glioblastoma following the failure of radiotherapy, temozolomide, and lomustine. A randomized trial comparing bevacizumab with best supportive care in these patients is advised.


Pulsing blue light through closed eyelids: effects on acute melatonin suppression and phase shifting of dim light melatonin onset.
Circadian rhythm disturbances parallel the increased prevalence of sleep disorders in older adults. Light therapies that specifically target regulation of the circadian system in principle could be used to treat sleep disorders in this population. Current recommendations for light treatment require the patients to sit in front of a bright light box for at least 1 hour daily, perhaps limiting their willingness to comply. Light applied through closed eyelids during sleep might not only be efficacious for changing circadian phase but also lead to better compliance because patients would receive light treatment while sleeping. Reported here are the results of two studies investigating the impact of a train of 480 nm (blue) light pulses presented to the retina through closed eyelids on melatonin suppression (laboratory study) and on delaying circadian phase (field study). Both studies employed a sleep mask that provided narrowband blue light pulses of 2-second duration every 30 seconds from arrays of light-emitting diodes. The results of the laboratory study demonstrated that the blue light pulses significantly suppressed melatonin by an amount similar to that previously shown in the same protocol at half the frequency (ie, one 2-second pulse every minute for 1 hour). The results of the field study demonstrated that blue light pulses given early in the sleep episode significantly delayed circadian phase in older adults; these results are the first to demonstrate the efficacy and practicality of light treatment by a sleep mask aimed at adjusting circadian phase in a home setting.


Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment.
To investigate the impact of fecal microbiota transplantation (FMT) treatment on allergic colitis (AC) and gut microbiota (GM). We selected a total of 19 AC infants, who suffered from severe diarrhea/hematochezia, did not relieve completely after routine therapy or cannot adhere to the therapy, and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT, and GM composition was assessed for infants and donors using 16S rDNA sequencing analysis. After FMT treatment, AC symptoms in 17 infants were relieved within 2 d, and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to follow-up. During follow-up, one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16S rDNA analysis in ten AC infants, most of them (n = 6) had greater GM diversity after FMT. As a result, Proteobacteria decreased (n = 6) and Firmicutes increased (n = 10) in post-FMT AC infants. Moreover, Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level, Bacteroides (n = 6), Escherichia (n = 8), and Lactobacillus (n = 4) were enriched in some AC infants after FMT treatment, but the relative abundances of Clostridium (n = 5), Veillonella (n = 7), Streptococcus (n = 6), and Klebsiella (n = 8) decreased dramatically. FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.


Full expression of Bacillus anthracis toxin gene in the presence of bicarbonate requires a 2.7-kb-long atxA mRNA that contains a terminator structure.
Bacillus anthracis toxin gene expression requires AtxA, a virulence regulator that also activates capsule gene transcription and controls expression of more than a hundred genes. Here we report that atxA mRNA is 2.7-kb-long and ends, after a 500 nt-long 3' untranslated region, with a stem loop structure followed by a run of U's. The presence of this structure stabilizes atxA mRNA and is necessary for AtxA maximal accumulation, full expression of the PA toxin gene, pagA and optimal PA accumulation. This structure displays terminator activity independently of its orientation when cloned between an inducible promoter and a reporter gene. The 3.6-kb-long DNA fragment carrying both AtxA promoters and the terminator is sufficient for full expression of pagA in the presence of bicarbonate. No pXO1-encoded element other than the DNA fragment encompassing the 2.7 kb atxA transcript and the pagA promoter is required for bicarbonate induction of pagA transcription.


Transitions of later life.
Each life event and turning point requires a transition in the life of the older individual. An older person's ability to make a transition successfully and to adjust to a new relationship with the environment depends on the type and the timing of the event. It also depends on the person's perception of the event, previous experiences and degree of freedom to explore a broad range of possibilities for the future.


Reconstruction of ear helix: use of self-tubing pedicle flap.
The tube pedicle flap is useful in reconstruction of an absent ear helix. However, immediate tubing of the flap may result in vascular compromise. By elevating a bipedicle flap in the postauricular region and shielding it with a silicone sheet, it is possible to allow the flap to assume a tubular shape while preventing adherence to the underlying suture line. Once mature, the flap maintains both a cylindrical shape and a sufficiently thin external diameter to provide adequate restoration of the ear helix.


Production, characterization and application of monoclonal antibody against immunoglobulin D heavy chain of flounder (Paralichthys olivaceus).
Immunoglobulin D (IgD) is considered to be an enigmatic Ig molecule because of the lack understanding of its immunological functions. In the present study, a partial δ region of the flounder IgD was recombinantly expressed, purified and used as an immunogen to produce monoclonal antibodies (MAbs) against the H chain of flounder IgD. After fusion, a total of 97 hybridomas were generated and observed under an inverted microscope One of the hybridomas, designated 5G7, gave strong positive results in an indirect enzyme-linked immunosorbent assay (ELISA) and was cloned and subcloned by limiting dilution. Western blot analysis showed that MAb 5G7 could specifically recognize a 118 kDa protein from peripheral blood lymphocytes (PBLs), which was identified to be the H chain of flounder IgD by mass spectrometric analysis. Indirect immunofluorescence assay tests (IIFAT) showed that specific fluorescence signals were observed on the membranes of the PBLs, which suggests that MAb 5G7 could recognize the membrane-bound IgD molecule. Moreover, only the subset of IgD+/IgM + B cells were observed in the PBLs of healthy flounder when tested by flow cytometry analysis. Consistent with the results of flow cytometry, a double immunofluorescence assay test (DIFAT) showed that the positive lymphocytes were stained with both green and red fluorescence signals, which represent the IgM+/IgD + lymphocytes subset. These results demonstrate that the produced MAb 5G7 could specifically recognize the flounder IgD, which provides a useful tool to study the functions of flounder IgD.


Perception of differentiation cues by GATA factors in primitive endoderm lineage determination of mouse embryonic stem cells.
The formation of the primitive endoderm covering the inner cell mass of early mouse embryos can be simulated in vitro by the differentiation of mouse embryonic stem (ES) cells in culture following either aggregation of suspended cells or stimulation of cell monolayers with retinoic acid. The developmentally regulated transcription factors GATA-4 and GATA-6 have determining role in mouse extraembryonic endoderm development. We analyzed the in vitro differentiation of mouse embryonic stem cells deficient of GATA factors and conclude that GATA-4 is required for ES cells to perceive a cell positioning (cell aggregation) signal and GATA-6 is required to sense morphogenic (retinoic acid) signal. The collaboration between GATA-6 and GATA-4, or GATA-6 and GATA-5 which can substitute for GATA-4, is involved in the perception of differentiation cues by embryonic stem cells in their determination of endoderm lineage. This study indicates that the lineage differentiation of ES cells can be manipulated by the expression of GATA factors.


Patient-Centered Goal-Setting in the National Diabetes Prevention Program: A Pilot Study.
Difficulty achieving preset goals (e.g., ≥5% weight loss, ≥150 min of weekly physical activity) in the yearlong National Diabetes Prevention Program (NDPP) can prompt dropout and diminish benefits. We piloted a more patient-centered NDPP adaptation (NDPP-Flex) that promotes a variety of attainable and individually tailored goals to reduce diabetes risks, along with flexibility to adjust goals each week as needed. Retention, physical activity, weight, and glycated hemoglobin (HbA1c) were evaluated among diverse participants with diabetes risks who received our pilot of NDPP-Flex beginning in January and July 2018 (n = 95), with a planned comparison with standard NDPP delivery in preceding cohorts that launched between September 2016 and October 2017 (n = 245). Both the standard NDPP and NDPP-Flex interventions were 1 year in duration and implemented in phases (i.e., nonrandomized). Average adjusted retention (e.g., 158.90 ± 15.20 vs. 166.71 ± 9.38 days; P = 0.674), physical activity (157.97 ± 11.91 vs. 175.64 ± 7.54 weekly min; P = 0.231), and weight loss (1.46 ± 0.38% vs. 1.90 ± 0.24%; P = 0.396) were similar between NDPP-Flex versus standard NDPP. However, NDPP-Flex participants had greater HbA1c reduction on average (0.22 ± 0.05% vs. 0.06 ± 0.03%; P = 0.018) and were more likely to have normoglycemia at follow-up (odds ratio 4.62; P = 0.013 [95% CI 1.38-15.50]) than participants in the standard NDPP. An adapted, more patient-centered NDPP that focuses on flexible, self-selected goals may be a promising strategy to improve glycemia even in the absence of substantial weight loss.


Structure-stability relationship in proteins: fundamental tasks and strategy for the development of stabilized enzyme catalysts for biotechnology.
The problem of relationships between the protein structure and its stability comprises two major questions. First, how to elucidate the peculiarities of the protein structure responsible for its stability. Second, knowing the general molecular basis of protein stability, how to change the structure of a given protein in order to increase its stability. This review is an attempt to show the modern state of the first (fundamental) and the second (applied) aspects of the problem.


Modernizing quality of life assessment: development of a multidimensional computerized adaptive questionnaire for patients with schizophrenia.
Quality of life (QoL) is still assessed using paper-based and fixed-length questionnaires, which is one reason why QoL measurements have not been routinely implemented in clinical practice. Providing new QoL measures that combine computer technology with modern measurement theory may enhance their clinical use. The aim of this study was to develop a QoL multidimensional computerized adaptive test (MCAT), the SQoL-MCAT, from the fixed-length SQoL questionnaire for patients with schizophrenia. In this multicentre cross-sectional study, we collected sociodemographic information, clinical characteristics (i.e., duration of illness, the PANSS, and the Calgary Depression Scale), and quality of life (i.e., SQoL). The development of the SQoL-CAT was divided into three stages: (1) multidimensional item response theory (MIRT) analysis, (2) multidimensional computerized adaptive test (MCAT) simulations with analyses of accuracy and precision, and (3) external validity. Five hundred and seventeen patients participated in this study. The MIRT analysis found that all items displayed good fit with the multidimensional graded response model, with satisfactory reliability for each dimension. The SQoL-MCAT was 39% shorter than the fixed-length SQoL questionnaire and had satisfactory accuracy (levels of correlation >0.9) and precision (standard error of measurement <0.55 and root mean square error <0.3). External validity was confirmed via correlations between the SQoL-MCAT dimension scores and symptomatology scores. The SQoL-MCAT is the first computerized adaptive QoL questionnaire for patients with schizophrenia. Tailored for patient characteristics and significantly shorter than the paper-based version, the SQoL-MCAT may improve the feasibility of assessing QoL in clinical practice.


Binary to unary transition problem in nucleation theory.
The limiting behavior in binary nucleation theory when one component vanishes is examined. Failure of the traditional continuum theory to predict the transition from binary to unary nucleation is due to breakdown of the continuum approximation. A semidiscrete model is constructed for the transition regime. For binary systems of arbitrary composition, a general formula that combines the semi-discrete and continuum nucleation rates is proposed. Comparison with the exact solution calculated using a fully discrete matrix method shows good agreement.


Non-recurrent laryngeal nerve in thyroid surgery.
A case of non-recurrent laryngeal nerve is reported. The non-recurrent laryngeal nerve was found on the right side and was not associated with any vascular abnormalities. The anatomy and surgical implication of this rare condition is discussed


Downregulation of Smac attenuates H2O2-induced apoptosis via endoplasmic reticulum stress in human lens epithelial cells.
Second mitochondria-derived activator of caspases (Smac) is reported to promote apoptosis. Given the important role of apoptosis in cataract development, the aim of this study was to investigate whether Smac induces human lens epithelial cell (HLEC) apoptosis via endoplasmic reticulum stress (ERS). Smac expression was examined by immunohistochemistry in anterior lens capsules from 157 patients with age-related cataracts and 5 normal controls. The role of Smac in hydrogen peroxide (H2O2)-induced ERS and apoptosis was further evaluated using small interfering RNA knockdown in an HLEC line. Notably, Smac expression was significantly higher in patients with cataracts than in controls, but showed no association with cataract severity. Cell survival was inversely correlated with H2O2 concentration, and was most significantly affected at 200 μmol/L. Moreover, flow cytometry revealed that Smac knockdown attenuated H2O2-induced apoptosis and enhanced apoptotic- and endoplasmic reticulum-related marker expression-including that of glucose-regulated protein 78, C/EBP homologous protein, caspase 3, B-cell chronic lymphocytic leukemia/lymphoma 2-associated X, and BCL2-at the gene and protein level. Collectively, these results indicate that Smac plays an important role in ERS-induced apoptosis in HLECs, suggesting its close association with cataract development.


Tiotropium bromide exerts anti-inflammatory activity in a cigarette smoke mouse model of COPD.
Tiotropium bromide is a long acting muscarinic antagonist (LAMA), marketed under the brand name Spiriva, for the treatment of chronic obstructive pulmonary disease (COPD). Besides its proven direct bronchodilatory activity, recent clinical studies demonstrated that tiotropium is able to reduce the exacerbation rate and impact the clinical course of COPD. One significant pathological feature believed to be causative for the progressive nature of COPD is chronic pulmonary inflammation. The aim of the present study was to investigate the anti-inflammatory activity of tiotropium on cigarette smoke-induced pulmonary inflammation in mice. C57Bl/6 mice were exposed to cigarette smoke (CS) for four days with increasing exposure time for up to 6h per day to elicit pulmonary inflammation and mediator release. One hour before smoke exposure, animals were treated with tiotropium by inhalation (0.01-0.3mg/mL) for 5 min; 18h after the last CS exposure a bronchoalveolar lavage was performed. Tiotropium concentration-dependently inhibited pulmonary neutrophilic inflammation with an IC(50) of 0.058 mg/mL and a maximum inhibition of 60% at 0.3mg/mL. Furthermore, the CS-induced pulmonary release of leukotriene B(4), interleukin-6, keratinocyte-derived chemokine, monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha and -2, and tumor necrosis factor alpha was dose-dependently reduced. The bronchodilatory activity of tiotropium against acetycholine-induced bronchoconstriction was found to be in the same dose range as the anti-inflammatory activity with an IC(50) of 0.045 mg/mL and a maximum bronchodilation of 90% at 0.3mg/mL. Our data suggest that the beneficial effects of tiotropium on the course of COPD shown in patients may be associated with an anti-inflammatory activity.


NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells.
Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase-1 (SK1) in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR-based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction in CO2 production. Additionally, SK1-expressing cells displayed a significant increase in glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support the biosynthesis of macromolecules. These findings highlight the role of SK1 signaling axis in cancer metabolic reprogramming, pointing out innovative strategies for cancer therapies.


The double-edged role of nitric oxide in brain function and superoxide-mediated injury.
Fetal ischemia or hypoxia can lead to cerebral palsy, mental retardation and epilepsy. We propose that the production of nitric oxide and oxygen radicals by neurons when ischemic or hypoxic brain is reperfused may contribute to cerebral injury. Ischemia will depolarize neuronal membranes causing the synaptic discharge of the excitatory neurotransmitter glutamate, which in turn opens the voltage-dependent, N-methyl-D-aspartic acid-specific glutamate receptor/ionophore, allowing calcium to accumulate in the neuron. Calcium in turn activates an oxygen-dependent neuronal nitric oxide synthetase, which oxidizes arginine to produce nitric oxide (.NO) when oxygen is readmitted to brain by reperfusion. Nitric oxide reacts with the oxygen radical superoxide (O2-), also produced by reperfusion, to form peroxynitrite (ONOO-). Peroxynitrite can diffuse for several micrometers before decomposing to form the powerful and cytotoxic oxidants hydroxyl radical and nitrogen dioxide. The hypothesis is consistent with available evidence on the protective action of glutamate antagonists and of oxygen radical scavengers for limiting cerebral infarction following focal ischemia.


The true sagittal diameter of the cervical spinal canal and its diagnostic significance in cercical myelopathy.
A method is presented for measuring the true sagittal diameter of the cervical spinal canal on routine lateral radiograms by the use of a midline perforated ruler. Sagittal measurements were made in 92 normal adults to establish a range of normal values. The lower and upper limits were 10 mm and 17 mm, respectively, at the levels of C-3 to C-7. Comparison of the results with the anatomical measurements of dried specimens showed good agreement. Four cases of cord compression were presented and the diagnostic significance of the method in cervical myelopathy was discussed.


Left ventricular hypertrophy: diagnostics pitfalls.
Isolated left ventricular hypertrophy, in the absence of hypertension or aortic stenosis, is commonly attributed to hypertrophic cardiomyopathy (HCM). According to the clinical setting, however, other differential diagnoses should be considered. The diagnosis of cardiac amyloidosis may be very challenging especially when the clinician is confronted with various aspects typical of both pathologies. The work-up of this case shows how non-invasive cardiac investigations are sometimes not sufficiently conclusive for distinguishing between the two pathologies, and that only endomyocardial biopsy (EMB) can confirm cardiac involvement secondary to systemic amyloidosis. The prognostic and therapeutic differences between the two diseases, as well as the contextual aspects of the case in point--namely a case of multiorgan failure--serve as an example of how a definitive diagnosis can be attained by means of a multidisciplinary approach in order to reach a definitive treatment plan.


Regenerator dependent photoinduced desorption of a dicarboxylated cyanine dye from the surface of single-crystal rutile.
A photon-initiated desorption of a dicarboxylated thiacarbocyanine dye from a dye-sensitized semiconducting oxide crystal has been observed when hydroquinone is used as a regenerator. No desorption was found under the same conditions when KI was used as the regenerator. Intermittent illumination experiments suggest that the oxidation products of the hydroquinone regenerator compete for dye adsorption sites. By comparing the photocurrent decay at both the dye monomer sensitization maximum and the dimer sensitization maximum, a rearrangement of monomer into dimer was observed. A kinetic model for the photocurrent decay as a function of desorption time was derived, and the desorption rate constants were obtained by fitting the experimental data to the model.


Budesonide for induction of remission in Crohn's disease.
Corticosteroids continue to play a central role in induction of remission in active Crohn's disease. However, their use comes at a price of significant adverse effects when used repeatedly or for extended periods. Newer corticosteroid agents with limited systemic bioavailability offer a tantalizing option, if they can be shown to be efficacious and safer than conventional corticosteroids. Budesonide is the main alternative corticosteroid currently available in an enteric formulation. To evaluate the effectiveness of oral budesonide for the treatment of acute flares of Crohn's disease. A secondary but important endpoint was to evaluate the adverse effect profile. The following sources were used to search the literature for potentially relevant papers and trials. 1. A computer-assisted search of the on-line bibliographic database MEDLINE from 1986 onwards. 2. Hand searching the reference lists of trials and review articles identified by means of the computer- assisted search. 3. Proceedings from major gastrointestinal meetings were manually searched from 1990 onwards. 4. Contact with the relevant pharmaceutical companies that have been involved in the development of budesonide. Potentially relevant articles were reviewed in an independent unblinded fashion by two authors to determine if they met the criteria specified below: 1) STUDY POPULATION: Patients of any age with acutely active Crohn's disease, as defined by a CDAI > 150. 2) METHODOLOGY: Randomized double blind controlled trials comparing budesonide to a control treatment. Patients in the control arm may have received placebo, conventional corticosteroids, 5-aminosalicylic acid or sulfasalazine. 3) OUTCOME MEASURES: Clinical remission was the outcome measure of interest. The definition of remission was usually a CDAI < 150 by 8 to 16 weeks of therapy. Eligible articles were reviewed in duplicate and the results of the primary research trials were abstracted onto specially designed data extraction forms. The proportion of patients achieving remission in the active treatment and control groups of each study were derived from the data provided in the original research papers. Where possible, data were broken down based on site of disease or other strata used by the individual trials. Data extracted from the original research articles were converted, where necessary, into individual 2 x 2 tables (remission versus no remission x budesonide versus control) for each of the individual studies. Where available, individual 2 x 2 tables for strata within studies were also used. The presence of significant heterogeneity among studies was tested for using the chi-square test. Because this is a relatively insensitive test for the presence of heterogeneity, a p-value of 0.10 was regarded as statistically significant. Where p < 0.10 the data from the individual studies were still combined but the pooled results were interpreted with caution. The 2 x 2 tables were synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel. A fixed effects model was used for the pooling of data. The analysis was performed initially by combining data from all trials to estimate the response rate to budesonide therapy. The analysis was also performed by combining only studies with comparable control groups. Eight studies were deemed eligible for review. Budesonide was superior to placebo for induction of remission with a pooled odds ratio for the two placebo-controlled trials of 2.85 (95% CI 1.67 - 4.87). A single trial comparing budesonide with mesalamine demonstrated an odds ratio of 2.80 (95% CI 1.50 - 5.20) in favour of budesonide over mesalamine for induction of remission in active Crohn's disease. However, budesonide was inferior to conventional corticosteroids (prednisone or prednisolone) for induction of remission with a pooled odds ratio for the five trials of 0.69 (95% CI 0.51 - 0.95). The two trials comparing budesonide versus placebo (Greenberg 1994; Tremaine 2002) showed no difference between study groups for proportion of reported corticosteroid-related adverse effects with the pooled odds ratio for both trials of 0.98 (95% CI 0.58 - 1.67). Five trials comparing budesonide versus prednisone showed the budesonide study group had fewer reported corticosteroid-related adverse effects than the prednisone study group (pooled odds ratio was 0.38 (95% CI 0.28 - 0.53). With disease in the ileum or ascending colon, budesonide offers an effective therapy which is somewhat less efficacious but with fewer adverse effects than conventional corticosteroids (e.g. prednisone, prednisolone, or 6-methylprednisolone).


Detection of Complexes in Biological Networks Through Diversified Dense Subgraph Mining.
Protein-protein interaction (PPI) networks, providing a comprehensive landscape of protein interaction patterns, enable us to explore biological processes and cellular components at multiple resolutions. For a biological process, a number of proteins need to work together to perform a job. Proteins densely interact with each other, forming large molecular machines or cellular building blocks. Identification of such densely interconnected clusters or protein complexes from PPI networks enables us to obtain a better understanding of the hierarchy and organization of biological processes and cellular components. However, most existing graph clustering algorithms on PPI networks often cannot effectively detect densely connected subgraphs and overlapped subgraphs. In this article, we formulate the problem of complex detection as diversified dense subgraph mining and introduce a novel approximation algorithm to efficiently enumerate putative protein complexes from biological networks. The key insight of our algorithm is that instead of enumerating all dense subgraphs, we only need to find a small diverse subset of subgraphs that cover as many proteins as possible. The problem is modeled as finding a diverse set of maximal dense subgraphs where we develop highly effective pruning techniques to guarantee efficiency. To scale up to large networks, we devise a divide-and-conquer approach to speed up the algorithm in a distributed manner. By comparing with existing clustering and dense subgraph-based algorithms on several yeast and human PPI networks, we demonstrate that our method can detect more putative protein complexes and achieves better prediction accuracy.


Clinical use of extra-large self-expanding stents.
The aim of this study is to describe our clinical experience with an extra-large self-expandable stent specifically designed to treat aortic lesions (E-XL, Jotec GmbH, Hechingen, Germany), now commercially available in Europe. The E-XL was used at our Institution in 14 patients (mean age, 56±12 years; 9 males) with the following indications: improve proximal fixation (4 cases), type I endoleak (2 cases), aortic dissection with static malperfusion (1 case) and dynamic malperfusion (7 cases). Early results have been shown to be safe and effective in different clinical settings, including in emergency cases. This peculiar aortic stent could be useful in the armamentarium of the endovascular surgeon.


Physical Activity Domains/Recommendations and Leukocyte Telomere Length in U.S. Adults.
The purpose of this study was to examine the associations between different physical activity (PA) domains, PA recommendations, and leukocyte telomere length (LTL) using data from a nationally representative sample of U.S. adults in the National Health and Nutrition Examination Survey, 1999-2002. A total of 6933 U.S. adults (3402 men, 3531 women; age range: 20-84 yr) who completed demographic, general health and PA questionnaires and provided a blood sample were included in the analyses. Multivariable-adjusted linear regression models were used to determine associations between PA (domain-specific PA [household/yard work PA, transportation PA, moderate leisure time PA (LTPA), and vigorous LTPA], total moderate PA and PA recommendation groups), and log-transformed LTL adjusting for age, gender, education, cigarette smoking, alcohol consumption, and body mass index. On average, an increase of 1 h·wk of vigorous LTPA was associated with a 0.31% (P < 0.001) longer LTL, and an increase of 1 h·wk of household/yard work PA was associated with a 0.21% (P = 0.03) shorter LTL while adjusted for sociodemographic and health behavior covariates. Neither transportation PA nor moderate LTPA was significantly associated with LTL. In addition, compared with not meeting the PA recommendation (<150 min·wk), exceeding the recommended PA levels (≥300 min·wk) was positively associated with longer LTL (P = 0.04), whereas there was no difference in telomere length between those not meeting versus those meeting the PA recommendation (150-299 min·wk). Greater engagement in vigorous LTPA and exceeding the PA recommendation may have a protective effect against telomere shortening. Future studies should examine the association between PA and LTL by exploring potential mediators such as sedentary behavior, genetics, nutrition, and chronic diseases.


Bed Bug (Cimex lectularius L.) Population Composition as Determined by Baited Traps.
Two established field populations of bed bugs were sampled using host-mimicking traps baited with a combination of CO2, heat and a synthetic kairomone. The proportion of first instar nymphs (between 52% and 78% of all captured insects) was significantly higher than reported in previous studies, which had employed different sampling methods. The proportion of adults was correspondingly much lower than previously reported, between 5% and 7% of total capture. As many as 120 bed bugs were captured in a single trap in one night; the variation in catches between sampling locations within the same room and between days at the same location indicates that multiple nights of trapping may be required to obtain an accurate representation of population structure.


Different tissue distribution and hormonal regulation of messenger RNAs encoding rat insulin-like growth factor-binding proteins-1 and -2.
The insulin-like growth factor-binding proteins IGFBP-1 and IGFBP-2 are low mol wt IGFBPs that are similar in structure. They are not glycosylated and have a homologous amino acid sequence, including the number and position of 18 cysteine residues and a carboxyl-terminal Arg-Gly-Asp sequence that can be recognized by cell adhesion receptors. The present study demonstrates that expression of mRNAs encoding the two BPs differs in some fetal rat tissues and in the livers of adult rats after hypophysectomy, fasting, or streptozotocin-induced diabetes. As determined by Northern blot hybridization using cDNA probes for rat IGFBP-2 or human IGFBP-1, both mRNAs are expressed at high levels in liver of 21-day gestation and 1-day-old rats and at lower levels in 21- and 65-day-old rat liver. Levels of both mRNAs are higher in liver than in other fetal rat tissues. The relative abundance of the two mRNAs in most fetal tissues is similar to that in liver, except that kidney and brain have 8-fold and more than 25-fold higher relative levels of IGFBP-2 mRNA, respectively. IGFBP-2 mRNA is about 10- to 20-fold increased after hypophysectomy or fasting, whereas IGFBP-1 mRNA is relatively unchanged. IGFBP-2 mRNA levels are decreased completely by refeeding fasted rats for 3 days, but only partially decreased by treatment of hypophysectomized rats with GH, cortisone acetate, T4, and testosterone for 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of SWL and URS on health-related quality of life in proximal ureteral stones.
We aimed to compare the effect of shock wave lithotripsy (SWL) and ureteroscopic lithotripsy (URS) on health-related quality of life (HRQoL) for the treatment of proximal ureteral stones. Between April 2014 and July 2015, patients with proximal ureteral stones who were successfully treated with URS or SWL in seven different centers were included. Patients were divided into two groups according to stone size: stones ≤10 mm and >10 mm. HRQoL subscales which were evaluated by the Medical Outcome Study Short-Form 36-item survey (SF-36) Turkish version were compared for URS and SWL in these two groups one month after the performed procedure. A total of 273 patients were included in the study. While 116 (52.5%) patients were treated with ureteroscopic lithotripsy, SWL was used for 105 (47.5%) patients. Fifty-two patients were excluded from the study. In proximal ureteral stones ≤10 mm, there were no statistically significant differences for any of the eight subscales of the SF-36 questionnaire. Regarding stones >10 mm, it was found that the three subscales of the SF-36 questionnaire - role limitations because of physical health problems (RP), bodily pain (BP), and general health perception (GH) - were significantly lower in the SWL group compared with the URS group. Patients with proximal ureteral stones >10 mm who were treated with URS generally may have a more favorable HRQoL than those treated with SWL in short-term follow-up.


Does the injection of platelet-rich plasma induce changes in the gene expression and morphology of intact Thoroughbred skeletal muscle?
Platelet-rich plasma (PRP) therapy is promising for treating skeletal muscle injuries in human athletes by promoting muscle regeneration. It might also be useful for treating muscle injuries in equine athletes. In the present study, muscle regeneration induced by injection of PRP into intact muscle of Thoroughbred was investigated. Autologous PRP and saline were injected twice into intact left and right gluteus medius muscles of seven clinically healthy Thoroughbreds. Muscle samples were collected from the injection sites by needle biopsy at 2 and 7 days after PRP injection. Immunohistochemical staining to identify the types of myosin heavy chains (MHCs) and satellite cells was performed to compare morphological changes among intact (pre-injection), saline-, and PRP-injected muscles. The expression of marker genes related to muscle regeneration (MHC-I, MHC-II, and embryonic MHC [MHC-e]), satellite cell activity (CK, Pax7, MyoD, and myogenin), and proinflammatory and promyogenic cytokines (IL-6, IGF-1, and HGF) was analyzed and compared between saline- and PRP-injected muscles. There were no obvious morphological differences among the three treatments. There were no significant differences in gene expression associated with satellite cell activity between saline and PRP injection at 7 days after injection. MHC genes showed significantly higher expression levels with PRP than with saline, including MHC-e at 2 days and MHC-I at 7 days after injection. It is suggested that injection of PRP into intact skeletal muscle does not induce specific morphological changes, but upregulate the expression of genes related to muscle regeneration.


Influence of the remelting process on the fatigue behavior of electron beam irradiated UHMWPE.
Electron beam irradiation at doses below 150 kGy is a widely used technique to obtain highly crosslinked ultra-high-molecular-weight polyethylene (UHMWPE). Its current use in total joint replacement components may improve wear resistance and decrease UHMWPE particle debris. However, currently used post-irradiation thermal treatments, which aim to decrease the free radicals within the material, introduce microstructural changes that affect UHMWPE mechanical properties, particularly the fatigue strength. This influence may be crucial in total knee replacements, where fatigue-related damage limits the lifespan of the prosthesis. Therefore, more studies are required to understand UHMWPE fatigue after current crosslinking protocols. This study was planned to evaluate the influence of UHMWPE remelting after irradiation on the material fatigue resistance. The remelting was achieved at 150 degrees C for 2 h on UHMWPE previously irradiated at 50, 100, and 150 kGy. Fatigue evaluation included short-term tests under cyclic tensile stress with zero load ratio, R = 0, and 1 Hz. In addition, stress-life testing was performed using 12% yield as the criterion for failure. Near-threshold fatigue crack propagation experiments were also performed at a frequency of 5 Hz, and crack length was measured in nonthermally treated and remelted irradiated UHMWPE. Crystallinity percentage was calculated from DSC measurements. The results pointed out that irradiation positively contributed to total life analysis, but the further remelting process decreased the flaw initiation resistance. On the other hand, both processes negatively affected the fatigue resistance of notched components. From a clinical point of view, the results suggest that the material fatigue behavior should be carefully studied in new UHMWPE to avoid changes related to material processing.


Intron-size constraint as a mutational mechanism in Rothmund-Thomson syndrome.
Rothmund-Thomson syndrome (RTS) is an autosomal recessive disorder caused by deleterious mutations in the RECQL4 gene on chromosome 8. The RECQL4 gene structure is unusual because it contains many small introns <100 bp. We describe a proband with RTS who has a novel 11-bp intronic deletion, and we show that this mutation results in a 66-bp intron too small for proper splicing. Constraint on intron size may represent a general mutational mechanism, since human-genome analysis reveals that approximately 15% of genes have introns <100 bp and are therefore susceptible to size constraint. Thus, monitoring of intron size may allow detection of mutations missed by exon-by-exon approaches.


Postpartum Stanford Type A Aortic Dissection: A Case Report and Review of the Literature.
Acute aortic dissection is a life-threatening disease. Approximately half of the aortic dissection observed in women under 45 years old has been reported to be related to pregnancy. Herein, we present a case of type A aortic dissection diagnosed in postpartum period. A 37-year-old woman admitted to the emergency department with the complaint of sudden onset of dyspnea. Arterial blood pressure was measured as 170/100 mmHg in left arm and 90/60 mmHg in right arm. With a prediagnosis of aortic dissection, thoracic and abdominal computed tomograpy was performed and type A aortic dissection extending form carotid artery to renal arterial level was detected. Operation of aortic dissection together with coronary arterial repairment and aortic valve replacement were successfully performed. Aortic dissection is not uncommon in pregnancy and furthermore it is potentially life-threatening for both mother and fetus. A high level of suspicion is required for prompt diagnosis and treatment in the peripartum period.


Sleep patterns, sleep disorders and mammographic density in spanish women: The DDM-Spain/Var-DDM study.
We explored the relationship between sleep patterns and sleep disorders and mammographic density (MD), a marker of breast cancer risk. Participants in the DDM-Spain/var-DDM study, which included 2878 middle-aged Spanish women, were interviewed via telephone and asked questions on sleep characteristics. Two radiologists assessed MD in their left craneo-caudal mammogram, assisted by a validated semiautomatic-computer tool (DM-scan). We used log-transformed percentage MD as the dependent variable and fitted mixed linear regression models, including known confounding variables. Our results showed that neither sleeping patterns nor sleep disorders were associated with MD. However, women with frequent changes in their bedtime due to anxiety or depression had higher MD (eβ:1.53;95%CI:1.04-2.26).


Breast cancer knowledge, beliefs, and screening behaviors among low-income, elderly black women.
This cross-sectional study explored whether there are age-specific differences in breast cancer-related knowledge, beliefs, and screening behaviors among low-income, elderly black women. Data were collected at senior citizen facilities from 214 black women aged 65 and older. Differences in knowledge, beliefs, and screening practices across three age groups were assessed by chi-square tests. Logistic regression modeling was used to determine the effect of these factors on compliance with American Cancer Society (ACS) screening guidelines. Age was inversely associated with knowledge and screening practices. The youngest group (65-74) was about twice as likely as the oldest group (85 and over) to correctly recognize breast cancer risk factors. About 50% of the oldest women compared to about 20% of the youngest women believed their risk for breast cancer was nil. The oldest group was also least likely to have had a mammogram or clinical breast examination within the past year, as recommended by the ACS. Our results suggest that educating elderly women, especially those 85 and over, about breast cancer and screening may lead to higher compliance with ACS recommendations.


Absence of the mitochondrial translocator protein 18 kDa in mice does not affect body weight or food intake responses to altered energy availability.
Changes in mitochondrial function in a variety of cells/tissues are critical for orchestrating systemic energy homeostasis and are linked to the development of obesity and many of its comorbidities. The mitochondrial translocator protein of 18 kDa (TSPO) is expressed in organs throughout the body, including the brain, liver, adipose tissue, gonads and adrenal glands, where it is implicated in regulating steroidogenesis and cellular metabolism. Prior work from our group and others has shown that, in rodents, TSPO levels are altered in adipose tissue by obesity and that modulation of TSPO activity may impact systemic glucose homeostasis. Furthermore, in vitro studies in a variety of cell types have implicated TSPO in mediating cellular energetics and substrate utilisation. Although mice with germline global TSPO deficiency (TSPO-/- ) have no reported changes in body weight under standard husbandry conditions, we hypothesised that, given the roles of TSPO in regulating mitochondrial function and cellular metabolic flexibility, these animals may have alterations in their systemic response to altered energy availability, either nutritional excess or insufficiency. In agreement with published work, compared to wild-type (TSPO+/+ ) littermates, TSPO-/- mice of both sexes did not exhibit differences in body weight on standard chow. Furthermore, following a 12-hour overnight fast, there was no difference in weight loss or compensatory food intake during re-feeding. Five weeks of feeding a high-fat diet (HFD) did not reveal any impact of the absence of TSPO on body weight gain in either male or female mice. Basal blood glucose levels and glucose clearance in a glucose tolerance test were influenced by feeding a HFD diet but not by genotype. In conclusion, in the paradigms examined, germline global deletion of TSPO did not change the physiological response to deviations in systemic energy availability at the whole organism level.


The current malaria morbidity and mortality in different transmission settings in Western Kenya.
Passive surveillance of malaria in health facilities remains vital for implementation of control and elimination programs. It is therefore essential understanding current age profile of clinical malaria morbidity, mortality and presentations in areas with variant infection susceptibility. This study aimed at understanding the current malaria morbidity and mortality in Western Kenya. Surveillance of clinical and asymptomatic parasitological positivity rates of all malaria suspected patients and school children were respectively determined from June 2015 to August 2016. From 2014 to 2016, register books in hospitals were referred and the confirmed malaria cases in conjunction with total number of monthly outpatient visits (OPD) counted. All registered malaria admissions were counted together with other causes of admissions. Moreover, outcome of malaria admissions in terms of discharge or death was recorded using inpatient charts within the same time frame. Prospective surveillance of severe malaria collected information on clinical features of the disease. Giemsa stained blood slides confirmed existence of malaria parasitemia. Chi-square and analysis of variance tests were used, respectively, to compute proportions and means; then a comparison was made between different age groups, periods, and study areas. During the survey of asymptomatic infections among school children, overall blood slide positivity ranged from 6.4% at the epidemic prone site to 38.3% at the hyperendemic site. During the clinical malaria survey, school age children (5-14) presented with overall the highest (45%) blood slide positivity rate among those suspected to have the infection at the epidemic prone study site. The survey of all malaria confirmed and registered cases at OPD found 17% to 27% of all consultations among <5 children and 9.9% to 20.7% of all OPD visits among the ≥5 patients were due to malaria. Moreover, survey of all registered causes of admission in hospitals found 47% of admissions were due to malaria. The disease was a major cause of admission in epidemic prone setting where 63.4% of the <5 children and 62.8% of the ≥5 patients were admitted due to malaria (p>0.05) and 40% of all malaria admissions were school age children. Malaria related death rate was highest among <5 years at the hyperendemic site, that is 60.9 death per 1000 malaria <5 admissions. Conversely, the epidemic prone setting experienced highest malaria related death among ≥15 years (18.6 death per 1000 admissions) than the < 15 years (5.7 death per 1000 admissions of the <15 years) (p< 0.001). Surveillance of severe form of the disease found that hyperpyrexia, hyperparastemia, prostration and convulsions as common presentations of severe disease. Malaria is still the major cause of hospital consultations in Western Kenya with an alarming number of severe forms of the disease among the school aged children at the epidemic prone setting. Mortalities were higher among <5 children years in high infection transmission setting and among ≥15 years in low and moderate transmission settings. Surveillance of asymptomatic and symptomatic malaria along with evaluation of current interventions in different age groups should be implemented in Kenya.


A simulation framework for reciprocal recurrent selection-based hybrid breeding under transparent and opaque simulators.
Hybrid breeding is an established and effective process to improve offspring performance, while it is resource-intensive and time-consuming for the recurrent process in reality. To enable breeders and researchers to evaluate the effectiveness of competing decision-making strategies, we present a modular simulation framework for reciprocal recurrent selection-based hybrid breeding. Consisting of multiple modules such as heterotic separation, genomic prediction, and genomic selection, this simulation framework allows breeders to efficiently simulate the hybrid breeding process with multiple options of simulators and decision-making strategies. We also integrate the recently proposed concepts of transparent and opaque simulators into the framework in order to reflect the breeding process more realistically. Simulation results show the performance comparison among different breeding strategies under the two simulators.


Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria.
To investigate the effects ofellagic acid (EA) on the cytotoxicity, B-lymphocytes isolated from CLL patients and healthy individuals. Flow cytometric assay was used to measure the percentage of apoptosis versus necrosis, intracellular active oxygen radicals (ROS), mitochondrial membrane potential (MMP) and the caspase-3 activity and then mitochondria were isolated from both groups B-lymphocytes and parameters of mitochondrial toxicity was investigated. Based on our results EA decreased the percentage of viable cells and induced apoptosis. EA increased ROS formation, mitochondria swelling, MMP decrease and cytochrome c release in mitochondria isolated from CLL BUT NOT healthy B-lymphocytes while pre-treatment with cyclosporine A and Butylated hydroxyl toluene (BHT) prevented these effects. Our results suggest that EA can act as an anti cancer candidate by directly and selectively targeting mitochondria could induce apoptosis through mitochondria pathway with increasing ROS production which finally ends in cytochrome c release, caspase 3 activation and apoptosis in cancerous B-lymphocytes isolated from CLL patients.


Gang-related homicides in Los Angeles County.
The incidence of gang homicides in Los Angeles County has increased faster than that of non-gang homicides in the past decade. This study compares characteristics of gang homicide victims with those of non-gang homicide victims for the year 1987. In 1186 cases, gang members were more likely to be young Black men who died of gunshot wounds. Gang homicide victims were more likely to die of firearm injuries in the early evening, and were more likely to die in a relatively small area of Los Angeles County. Drive-by shooting was highly associated with gang homicide.


Immunohistochemical analysis of the retrobulbar tissues in Graves' ophthalmopathy.
We have characterized the mononuclear cell infiltrate in the extraocular muscle of three patients with Graves' disease, using antibodies which permit staining of paraffin-embedded tissue. The majority of lymphocytes, occurring in foci or interstitially, were T cells, most of which stain for CD3 or with UCHL1. T cells few, if any, stained with SN130, directed against the CD45R determinant. This suggests that these lymphocytes comprise a recently activated population within which memory cells may reside. B cells were also found but were predominantly confined to focal aggregates, and in one patient lymphoid follicles were seen. The orbital fat and connective tissue from a further two patients contained very few infiltrating cells which were mainly UCHL1-positive. Eye muscle cells did not express Ia antigens but the interstitial cells between them were Ia-positive and the vascular endothelium in four of the five specimens also stained with Ia. These results indicate that Graves' ophthalmopathy is associated with T cell, and to a lesser extent B cell, responses against the retrobulbar tissues; the extraocular muscle interstitial cells, probably including fibroblasts, may be targets of activation resulting from this infiltration.


Evaluation of the physical stability of two oleogels.
Oleogels are semisolid systems obtained with an organogelator and a hydrophobic liquid that have been investigated over the past few years and that could play an important role as dermatological bases. Recently, we have developed an oleogel of sorbitan monostearate (19wt.%) and sweet almond oil (SM-SAO) and another one of cholesterol (3.5wt.%) and liquid paraffin (Ch-LP). The aim of this work is to access their physical stability using three different methodologies. The gels were stored at different temperatures (20 and 40 degrees C) over a 3-month period. Appearance and textural properties were assessed on each month. An accelerated test was also performed where the temperature changed between 4 and 40 degrees C every 24h, during 7 days. Rheological tests were also carried out as they could provide useful elements to predict stability. The gels were quite stable at 20 degrees C, being the SM-SAO gel the most stable. The textural properties of both gels were influenced by temperature. The decrease of the textural parameters, observed after storage at 40 degrees C and in the cycling test, was more significant for the SM-SAO gel. A good correlation was found between rheological analysis and conventional stability tests. The heating/cooling cycle test provided useful information in a short period of time.


Bibliometric Analysis of Moxibustion Research Trends over the Past 20 Years.
A bibliometric approach using network analysis was applied to identify the development and research trends for moxibustion. This study also examined the network hub of moxibustion research by investigating the collaborative work of organizations and authors. Academic articles on moxibustion research published from 2000 to 2019 were retrieved from the Web of Science database. Extracted records were analyzed according to publication year, research area, journal title, country, organization, and authors. The VOSviewer program was utilized to visualize the trends in moxibustion research and to explore the influential organizations and authors. Analyses of 1146 original and review articles written in English demonstrated that the number of publications related to moxibustion research has increased consistently over the last 20 years. China issued the most articles in this field, and the most represented research area was integrative complementary medicine. A network analysis based on the co-occurrence and publication year of keywords identified the relevant characteristics and trends of moxibustion research. By assessing the total link strength of organizations and authors, influential organizations and authors who have contributed to moxibustion research were identified. The current study examined research on moxibustion using bibliometric analysis and identified a time-based development of moxibustion research and a global network hub of moxibustion research.


Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice.
The type 1 deiodinase (D1) is thought to be an important source of T3 in the euthyroid state. To explore the role of the D1 in thyroid hormone economy, a D1-deficient mouse (D1KO) was made by targeted disruption of the Dio1 gene. The general health and reproductive capacity of the D1KO mouse were seemingly unimpaired. In serum, levels of T4 and rT3 were elevated, whereas those of TSH and T3 were unchanged, as were several indices of peripheral thyroid status. It thus appears that the D1 is not essential for the maintenance of a normal serum T3 level in euthyroid mice. However, D1 deficiency resulted in marked changes in the metabolism and excretion of iodothyronines. Fecal excretion of endogenous iodothyronines was greatly increased. Furthermore, when compared with both wild-type and D2-deficient mice, fecal excretion of [125I]iodothyronines was greatly increased in D1KO mice during the 48 h after injection of [125I]T4 or [125I]T3, whereas urinary excretion of [125I]iodide was markedly diminished. From these data it was estimated that a majority of the iodide generated by the D1 was derived from substrates other than T4. Treatment with T3 resulted in a significantly higher serum T3 level and a greater degree of hyperthyroidism in D1KO mice than in wild-type mice. We conclude that, although the D1 is of questionable importance to the wellbeing of the euthyroid mouse, it may play a major role in limiting the detrimental effects of conditions that alter normal thyroid function, including hyperthyroidism and iodine deficiency.


BMP9 and BMP10: Two close vascular quiescence partners that stand out.
Bone morphogenetic proteins (BMPs) are dimeric transforming growth factor ß (TGFß) family cytokines that were first described in bone and cartilage formation but have since been shown to be involved in many pleiotropic functions. In human, there are 15 BMP ligands, which initiate their cellular signaling by forming a complex with two copies of type I receptors and two copies of type II receptors, both of which are transmembrane receptors with an intracellular serine/threonine kinase domain. Within this receptor family, ALK1 (activin receptor-like kinase 1), which is a type I receptor mainly expressed on endothelial cells, and BMPRII (BMP Receptor type II), a type II receptor also highly expressed on endothelial cells, have been directly linked to two rare vascular diseases: hereditary hemorrhagic telangiectasia (HHT), and pulmonary arterial hypertension (PAH), respectively. BMP9 (gene name GDF2) and BMP10, two close members of the BMP family, are the only known ligands for the ALK1 receptor. This specificity gives them a unique role in physiological and pathological angiogenesis and tissue homeostasis. The aim of this current review is to present an overview of what is known about BMP9 and BMP10 on vascular regulation with a particular emphasis on recent results and the many questions that remain unanswered regarding the roles and specificities between BMP9 and BMP10.


Distal Clavicular Osteochondral Autograft Augmentation for Glenoid Bone Loss: A Comparison of Radius of Restoration Versus Latarjet Graft.
Bone loss in shoulder instability is a well-recognized cause of failure after stabilization surgery. Many approaches have been described to address glenoid bone loss, including coracoid transfer. This transfer can be technically difficult and has been associated with high complication rates. An ideal alternative to coracoid transfer would be an autologous source of fresh osteochondral graft with enough surface area to replace significant glenoid bone loss. The distal clavicle potentially provides such a graft source that is readily available and low-cost. To evaluate distal clavicular autograft reconstruction for instability-related glenoid bone loss, specifically comparing the width of the clavicular autograft with the width of an ipsilateral coracoid graft as prepared for a Latarjet procedure. Further, we sought to compare the articular cartilage thickness of the distal clavicle graft with that of the native glenoid. Controlled laboratory study. Twenty-seven fresh-frozen cadaver specimens were dissected, and an open distal clavicle excision was performed. The coracoid process in each specimen was prepared as has been described for a classic Latarjet coracoid transfer. In each specimen, the distal clavicle graft was compared with the coracoid graft for size and potential of glenoid articular radius of restoration. The distal clavicle graft was also compared with the native glenoid for cartilage thickness. In all specimens, the distal clavicle grafts provided a greater radius of glenoid restoration than the coracoid grafts ( P < .0001). On average, the clavicular graft was able to reconstruct 44% of the glenoid diameter, compared with 33% for the coracoid graft ( P < .0001). The articular cartilage of the glenoid was significantly thicker (1.4 mm thicker, P < .0001) than that of the distal clavicular autograft (average ± SD, 3.5 ± 0.6 mm vs 2.1 ± 0.8 mm, respectively). When specimens with osteoarthritis were excluded, this difference decreased to 0.97 mm when compared with the clavicular cartilage ( P = .0026). The distal clavicle autograft can restore a significantly greater glenoid bone deficit than the Latarjet procedure and has the additional benefit of restoring articular cartilage to the glenoid. The articular cartilage thickness of the distal clavicle is within 1.4 mm of that of the native glenoid. The distal clavicular autograft may be a suitable option for reconstruction of instability-related glenoid bone loss. This graft provides a structural osteochondral autograft with a broader radius of reconstruction than that of a coracoid graft, is locally available, has minimal donor site morbidity, is anatomic, and provides articular cartilage.


Self-Contained Neuromusculoskeletal Arm Prostheses.
We report the use of a bone-anchored, self-contained robotic arm with both sensory and motor components over 3 to 7 years in four patients after transhumeral amputation. The implant allowed for bidirectional communication between a prosthetic hand and electrodes implanted in the nerves and muscles of the upper arm and was anchored to the humerus through osseointegration, the process in which bone cells attach to an artificial surface without formation of fibrous tissue. Use of the device did not require formal training and depended on the intuitive intent of the user to activate movement and sensory feedback from the prosthesis. Daily use resulted in increasing sensory acuity and effectiveness in work and other activities of daily life. (Funded by the Promobilia Foundation and others.).


Patient Decision-Making About Emergency and Planned Stoma Surgery for IBD: A Qualitative Exploration of Patient and Clinician Perspectives.
Many inflammatory bowel disease (IBD) patients worry about stoma-forming surgery (SFS), sometimes enduring poor bowel-related quality of life to avoid it. Anticipation of SFS and whether expectations match experience is underreported. This qualitative study explored influences on patients' SFS decision-making and compared preoperative concerns with postoperative outcomes. We purposively recruited participants with IBD from UK hospital outpatient and community sources, and IBD clinicians from public hospitals. Four focus groups, 29 semistructured patient participant interviews, and 18 clinician interviews were audio recorded, transcribed, and analysed thematically. Participants had a current temporary, recently-reversed, or permanent stoma, or were stoma naive. Four themes emerged: Preoperative concerns and expectations, Patient decision-making, Surgery and recovery, and Long-term outcomes. Participants and clinicians agreed about most preoperative concerns, that outcomes were often better than expected, and support from others with a stoma is beneficial. Patient decision-making involves multiple factors, including disease status. Some clinicians avoid discussing SFS, and the phrase 'last resort' can bias patient perceptions; others recommend early discussion, increasing dialogue when medical management becomes ineffective. The postoperative period is particularly challenging for patients. Stoma acceptance is influenced by personal perceptions and pre- and postoperative clinical and social support. Patients need balanced information on all treatment options, including surgery, from an early stage. Early multidisciplinary team dialogue about SFS, and contact with others living well with a stoma, could enable informed decision-making. Life with a stoma is often better than anticipated, improving quality of life and control. Ongoing specialist nursing support aids recovery and adjustment.


Influence of Selected Factors on the Relationship between the Dynamic Elastic Modulus and Compressive Strength of Concrete.
In this paper, the relationship between the static and dynamic elastic modulus of concrete and the relationship between the static elastic modulus and compressive strength of concrete have been formulated. These relationships are based on investigations of different types of concrete and take into account the type and amount of aggregate and binder used. The dynamic elastic modulus of concrete was tested using impulse excitation of vibration and the modal analysis method. This method could be used as a non-destructive way of estimating the compressive strength of concrete.


Healthcare resource utilization and costs assessment of type 2 diabetes patients initiating exenatide BID or glargine: a retrospective database analysis.
To examine resource utilization and healthcare costs associated with the use of exenatide versus glargine in type 2 diabetes (T2D) patients. A retrospective analysis comprised of patients with T2D initiating exenatide (n = 7,255) or glargine (n = 2,819) between 04/01/2005 and 06/30/2007. Propensity score matching was used (2,506 matched pairs) to control for baseline demographic, clinical, resource use, and cost variables to balance treatment groups. Mean medical costs and other cost components were estimated using nonparametric bootstrapping. Exenatide-treated patients had 19% lower likelihood of all-cause hospitalizations (odds ratio [OR]: 0.81, p = 0.009) compared to glargine-treated patients. Exenatide-treated patients had significantly lower total medical costs of $2,597 (p = 0.008). Exenatide-treated patients had significantly lower inpatient costs of $1,968 (p = 0.004) and outpatient costs of $1,324 (p = 0.011), but higher prescription costs of $706 (p < 0.001). Exenatide-treated patients further incurred lower hospitalization costs of $1,910 (p = 0.005) and physician office visit costs of $608 (p = 0.008). Lack of availability of clinical measures including duration of diabetes, severity of T2D and lack of control for unmeasured confounding. Patients initiating exenatide treatment had significantly lower healthcare resource utilization and total medical costs. Cost offsets were observed in inpatient and outpatient costs despite higher prescription costs.


Digoxin and the geriatric in-patient. A randomized trial of digoxin versus placebo.
The effects of oral digoxin and placebo in 41 geriatric in-patients were compared using a randomized, double-blind, cross-over method. The patients were in sinus rhythm or had atrial fibrillation. The observation period was two months on digoxin or placebo. Patients with symptoms of cardiac failure at rest or during light physical activity, X-ray signs of pulmonary congestion, proven need of digoxin therapy following earlier withdrawal, atrial fibrillation with a ventricular rate greater than 95 beats/min and patients in whom digitalis intoxication was suspected were excluded from the study. Five (14%) of 37 patients deteriorated during the placebo phase. Four of these developed rapid atrial fibrillation and one patient developed sinus tachycardia and symptoms of heart failure.


Catalysis for fuels: Concluding Remarks.
The 2017 Faraday Discussion on the topic of "Catalysis for Fuels" was unique in the sense that it was the first Faraday Discussion to be held on the continent of Africa. "Catalysis" and "Fuels" are both topics that could be widely interpreted and the session topics proved to be a relevant spread of old and new i.e. Fischer-Tropsch chemistry, biomass refining, zeolite conversions and photocatalysis. Most of the papers were underpinned by fundamental studies, catalyst design approaches, reports of in operando characterization and detailed speciation and micro kinetic analyses. Examples of commercial application were offered under the headings of biomass conversion, Fischer-Tropsch and to some extent photocatalysis. Cognisance was given to the increasingly important role of catalytic metals in terms of scarcity, cost and environmental impact. The potential role of novel alloys in addressing some of the catalytic mechanistic challenges turned out to be one of the central themes during the discussions. The following remarks are an attempt to draw parallels between the topics under discussion and the author's subjective view of current universal questions that could/should be highlighted under the "Catalysis for Fuels" heading.


Bioethics at Monash University.
The history and development of the Centre for Human Bioethics at Monash University is briefly sketched. This is followed by a description of the Centre's aims, its structure, its staff, and its principal fields of research. Some recent publications of the Centre are then listed.


Differential sensing of protein influences by NO and CO vibrations in heme adducts.
Heme proteins bind the gaseous ligands XO (X = C, N, O) via backbonding from Fe d(pi) electrons. Backbonding is modulated by distal interactions of the bound ligand with the surrounding protein and by variations in the strength of the trans proximal ligand. Vibrational modes associated with FeX and XO bond stretching coordinates report on these interactions, but the interpretive framework developed for CO adducts, involving anticorrelations of nuFeC and nuCO, has seemed not to apply to NO adducts. We have now obtained an excellent anticorrelation of nuFeN and nuNO, via resonance Raman spectroscopy on (N-methylimidazole)Fe(II)TPP-Y(NO), where TPP-Y is tetraphenylporphine with electron-donating or -withdrawing substituents, Y, that modulate the backbonding; the problem of laser-induced dissociation of the axial base was circumvented by using frozen solutions. New data are also reported for CO adducts. The anticorrelations are supported by DFT calculations of structures and spectra. When protein data are examined, the NO adducts show large deviations from the modeled anticorrelation when there are distal H-bonds or positive charges. These deviations are proposed to result from closing of the FeNO angle due to a shift in the valence isomer equilibrium toward the Fe(III)(NO-) form, an effect that is absent in CO adducts. The differing vibrational patterns of CO and NO adducts provide complementary information with respect to protein interactions, which may help to elucidate the mechanisms of ligand discrimination and signaling in heme sensor proteins.


An evaluation of automated chest radiography reading software for tuberculosis screening among public- and private-sector patients.
Computer-aided reading (CAR) of medical images is becoming increasingly common, but few studies exist for CAR in tuberculosis (TB). We designed a prospective study evaluating CAR for chest radiography (CXR) as a triage tool before Xpert MTB/RIF (Xpert).Consecutively enrolled adults in Dhaka, Bangladesh, with TB symptoms received CXR and Xpert. Each image was scored by CAR and graded by a radiologist. We compared CAR with the radiologist for sensitivity and specificity, area under the receiver operating characteristic curve (AUC), and calculated the potential Xpert tests saved.A total of 18 036 individuals were enrolled. TB prevalence by Xpert was 15%. The radiologist graded 49% of CXRs as abnormal, resulting in 91% sensitivity and 58% specificity. At a similar sensitivity, CAR had a lower specificity (41%), saving fewer (36%) Xpert tests. The AUC for CAR was 0.74 (95% CI 0.73-0.75). CAR performance declined with increasing age. The radiologist grading was superior across all sub-analyses.Using CAR can save Xpert tests, but the radiologist's specificity was superior. Differentiated CAR thresholds may be required for different populations. Access to, and costs of, human readers must be considered when deciding to use CAR software. More studies are needed to evaluate CAR using different screening approaches.