[The value of closed reduction of fractures of the lower thoracic and lumbar spine and computerized tomography follow-up].
The objectives of this prospective study were to investigate the value of the immediate closed reduction following fractures of the thoracolumbar and lumbar region. To reach that goal we performed a two stage CAT scan procedure before and after the reduction maneuver in a distinct patient population. The aim was not only to investigate the biomechanical process but also to evaluate and describe certain fracture types which have a good prognosis due to closed reduction according to posttraumatic spinal stenosis because of protruding posterior wall fragments and those who fail, respectively.


Region-dependent role of the mucous/glycocalyx layers in insulin permeation across rat small intestinal membrane.
The regional difference in the contribution of the mucous/glycocalyx layers in rat small intestine, as a diffusional or enzymatic barrier, to the absorption of insulin was investigated by in vitro studies. The mucous/glycocalyx layers from the duodenum, the jejunum, and the ileum in rat were successfully removed without damaging membrane integrity, by exposing them to a hyaluronidase solution in situ. In an in vitro transport experiment, the apparent permeability coefficient (P(app)) of insulin for the hyaluronidase-pretreated group was significantly increased compared to the PBS-pretreated (control) group in all small intestinal regions, and the P(app) of insulin in both PBS- and hyaluronidase-pretreated groups increased in the following order: duodenum < jejunum < ileum. On the other hand, irrespective of small intestinal regions, the P(app) of FD-4 and of antipyrine, respectively the passive para- and transcellular permeation marker, exhibited no significant differences between PBS- and hyaluronidase-pretreated group. In addition, a significant amount of insulin was degraded in the mucous/glycocalyx layers compartment removed by hyaluronidase pretreatment, and the degradation activity in the mucous/glycocalyx layers showed regional differences in the following order: duodenum > jejunum > ileum. These findings suggest that, irrespective of small intestinal regions, the mucous/glycocalyx layers contributed to insulin permeation predominantly as an enzymatic barrier, and not as a diffusional barrier. Furthermore, the variation of the enzymatic activities in the mucous/glycocalyx layers and in the brush-border membrane would be one factor that accounts for the regional differences in the transport of insulin.


Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications.
We have recently described manufacturing of human induced pluripotent stem cells (iPSC) master cell banks (MCB) generated by a clinically compliant process using cord blood as a starting material (Baghbaderani et al. in Stem Cell Reports, 5(4), 647-659, 2015). In this manuscript, we describe the detailed characterization of the two iPSC clones generated using this process, including whole genome sequencing (WGS), microarray, and comparative genomic hybridization (aCGH) single nucleotide polymorphism (SNP) analysis. We compare their profiles with a proposed calibration material and with a reporter subclone and lines made by a similar process from different donors. We believe that iPSCs are likely to be used to make multiple clinical products. We further believe that the lines used as input material will be used at different sites and, given their immortal status, will be used for many years or even decades. Therefore, it will be important to develop assays to monitor the state of the cells and their drift in culture. We suggest that a detailed characterization of the initial status of the cells, a comparison with some calibration material and the development of reporter sublcones will help determine which set of tests will be most useful in monitoring the cells and establishing criteria for discarding a line.


SARS outbreaks in Ontario, Hong Kong and Singapore: the role of diagnosis and isolation as a control mechanism.
In this article we use global and regional data from the SARS epidemic in conjunction with a model of susceptible, exposed, infective, diagnosed, and recovered classes of people ("SEIJR") to extract average properties and rate constants for those populations. The model is fitted to data from the Ontario (Toronto) in Canada, Hong Kong in China and Singapore outbreaks and predictions are made based on various assumptions and observations, including the current effect of isolating individuals diagnosed with SARS. The epidemic dynamics for Hong Kong and Singapore appear to be different from the dynamics in Toronto, Ontario. Toronto shows a very rapid increase in the number of cases between March 31st and April 6th, followed by a significant slowing in the number of new cases. We explain this as the result of an increase in the diagnostic rate and in the effectiveness of patient isolation after March 26th. Our best estimates are consistent with SARS eventually being contained in Toronto, although the time of containment is sensitive to the parameters in our model. It is shown that despite the empirically modeled heterogeneity in transmission, SARS' average reproductive number is 1.2, a value quite similar to that computed for some strains of influenza (J. Math. Biol. 27 (1989) 233). Although it would not be surprising to see levels of SARS infection higher than 10% in some regions of the world (if unchecked), lack of data and the observed heterogeneity and sensitivity of parameters prevent us from predicting the long-term impact of SARS. The possibility that 10 or more percent of the world population at risk could eventually be infected with the virus in conjunction with a mortality rate of 3-7% or more, and indications of significant improvement in Toronto support the stringent measures that have been taken to isolate diagnosed cases.


Importance of self-weighing to avoid post-cessation weight gain: A secondary analysis of the fit and quit randomized trial.
Smoking cessation is associated with weight gain, and the risk of weight gain is a common deterrent to quitting smoking. Thus, the identification of strategies for reducing post-smoking cessation weight gain is critical. Conduct secondary analysis of data from the Fit & Quit trial to determine if greater frequency of self-weighing is associated with less weight gain in the context of smoking cessation. Participants (N = 305) were randomized to one of three 2-month weight interventions (i.e., Stability, Loss, Bibliotherapy), followed by a smoking cessation intervention. Stability and Loss conditions received different types of self-weighing feedback. All participants received e-scales at baseline, to capture daily self-weighing data over 12 months. General linear models were applied to test the main objective. Frequency of self-weighing was (mean ± SD) 2.67 ± 1.84 days/week. The Stability condition had significantly higher self-weighing frequency (3.18 ± 1.72 days/week) compared to the Loss (2.51 ± 1.99 days/week) and the Bibliotherapy conditions (2.22 ± 1.63 days/week). Adjusting for baseline weight and treatment condition, self-weighing 3-4 days/week was associated with weight stability (-0.77 kg, 95% CI: -2.2946, 0.7474, p = 0.3175), and self-weighing 5 or more days/week was associated with 2.26 kg weight loss (95% CI: -3.9249, -0.5953, p = 0.0080). Self-weighing may serve as a useful tool for weight gain prevention after smoking cessation. Feedback received about self-weighing behaviors and weight trajectory (similar to the feedback Stability participants received) might enhance adherence.


Morin inhibits interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes.
It is well known that the inflammatory cytokines play important roles in osteoarthritis (OA). In the present study, we investigated the anti-inflammatory properties of morin in chondrocytes. The nitric oxide (NO) production was determined by Griess method, the prostaglandin E2 (PGE(2)) production was detected by Enzyme-linked immunosorbent assay (ELISA). The expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were investigated by quantitative real-time PCR and western blot. In addition, western blotting and immunofluorescence staining were performed to investigate the protein level of inhibitor of nuclear factor-κB (IκB-α) and the translocation of nuclear factor kappa B (NF-κB). For the in vivo study, morin was administered by intra-articular injection in rats, and the gene expression of iNOS and COX-2 was assessed. We showed that morin inhibited the production of NO and PGE(2) as well as the expression of iNOS and COX-2 in interleukin-1-beta (IL-1β)-induced chondrocytes. In addition, morin suppressed the degradation of IκB-α as well as the translocation of NF-κB. In vivo study, morin exerted anti-inflammatory properties in an IL-1β-induced rat OA model. Our data suggest that morin possess potential value in the treatment of OA.


Inflammatory cytokines IFN-γ, IL-4, IL-13 and TNF-α alterations in schistosomiasis: a meta-analysis.
Cytokines play an important role in the immunological pathogenesis of schistosomiasis. Schistosomiasis would be associated with an imbalance in inflammatory cytokines that leads to a decrease of T helper (Th) 1 and an increase of Th2 cytokine secretion. Corresponding data so far have been inconsistent, so we performed a meta-analysis to assess whether cytokine alterations were risk factors for schistosomiasis progression. We searched MEDLINE, EMBASE, and CNKI databases for literatures including abstracts, reviews, and reference lists. Our studies included assessment of cytokine concentrations in vivo plasma or serum and secretion of cytokines in vitro by peripheral blood leukocytes from schistosomiasis patients or infected individuals with schistosome. The prototypic Th1 and Th2 cytokines IFN-γ and interleukin (IL)-4 were assessed as well as IL-13 and tumor necrosis factor-alpha (TNF-α). The results implied that an increase occurs in TNF-α and IL-4 with schistosomiasis progression.


Radio-immunoassay for formyl methionyl leucyl phenylalanine. II. Demonstration of an enterohepatic circulation of immunoreactive bacterial chemotactic peptides in man.
Bacterial chemotactic peptides (F-met-oligopeptides) are secreted by several species of commensal enteric bacteria and can be assayed by bioassay techniques in human colonic luminal fluid. We have previously demonstrated intestinal absorption and enterohepatic circulation of radiolabelled F-met peptides introduced into rat colon, and an eightfold increase in absorption and biliary excretion in rats with experimental colitis. This paper describes the application of a radio-immunoassay to measurements of formyl oligopeptides in human faecal dialysates, colonic and systemic venous blood and bile. All samples were fractionated by reverse-phase high performance liquid chromatography (HPLC) prior to assay. Immunoreactivity was found in faecal dialysates (5-700 nmol/L F-met-leu-phe equivalents) and bile samples (3-150 nmol/L) from normal subjects. After HPLC fractionation, up to five distinct peaks of immunoreactivity were identified. One of these co-chromatographed with authentic F-met-leu-phe; the others probably represented either closely related peptides or peptides of different chain lengths originating from the same F-met-leu-phe precursor protein. Colonic venous blood from two patients with ulcerative colitis contained immunoreactive peptide (10-30 nmol/L) and substantial immunoreactivity was found in ileostomy fluid and bile from two patients with primary sclerosing cholangitis. These results suggest the presence of an enterohepatic circulation of bacterial F-met oligopeptides in man and provide a basis for studies of the role of such pro-inflammatory peptides in patients with inflammatory bowel disease and associated hepatobiliary disorders.


Lethal Morel-Lavallée lesion: A forensic radiology-pathology correlation.
Morel Lavallée lesion or closed degloving injury is normally associated with severe trauma and occurs when the skin and subcutaneous fatty tissue traumatically and abruptly separated from the underlying fascia thus creating a potential space filled with fluid. MVA is the commonest etiology but large or lethal Morel Lavallée is extremely rare. A 35 years old, female pillion rider was involved in a motor vehicle accident and sustained injuries to the left pelvis and thigh. Emergency laparotomy and intra-op abdominal and bilateral lower limb arteriogram revealed no significant finding. Her general condition and vital signs continued to deteriorate despite aggressive resuscitation and eventually died. Post-Mortem Computed Tomography and Post-Mortem Computed Tomography Angiogram was performed and revealed a large cavity in the left thigh suggestive of a lethal Morel Lavallée lesion. Findings were confirmed by conventional autopsy.


Susceptibility of plasmenyl glycerophosphoethanolamine lipids containing arachidonate to oxidative degradation.
Plasmenyl phospholipids (1-alk-1'-enyl-2-acyl-3-glycerophospholipids, plasmalogens) are a structurally unique class of lipids that contain an alpha-unsaturated ether substituent at the sn-1 position of the glycerol backbone. Several studies have supported the hypothesis that plasmalogens may be antioxidant molecules that protect cells from oxidative stress. Because the molecular mechanisms responsible for the antioxidant properties of plasmenyl phospholipids are not fully understood, the oxidation of plasmalogens in natural mixtures of phospholipids was studied using electrospray tandem mass spectrometry. Glycerophosphoethanolamine (GPE) lipids from bovine brain were found to contain six major molecular species (16:0p/18:1-, 18:1p/18:1-, 18:0p/20:4-, 16:0p/20:4, 18:0a/20:4-, and 18:0a/22:6-GPE). Oxidation of GPE yielded lyso phospholipid products derived from plasmalogen species containing only monounsaturated sn-2 substituents and diacyl-GPE with oxidized polyunsaturated fatty acyl substituents at sn-2. The only plasmalogen species remaining intact following oxidation contained monounsaturated fatty acyl groups esterified at sn-2. The mechanism responsible for the rapid and specific destruction of plasmalogen GPE may likely involve unique reactivity imparted by a polyunsaturated fatty acyl group esterified at sn-2. This structural feature may play a central role determining the antioxidant properties ascribed to this class of phospholipids.


Value of microbiology study in congenital nasolacrimal duct obstruction.
Evaluation of the effect of different microorganisms on congenital nasolacrimal duct obstruction (CNLDO) tightness and whether probing or silastic intubation is likely to fail in a particular microorganism infection. The culture and sensitivity results of lacrimal drainage system (LDS) discharge samples from patients with CNLDO were reviewed. Different microorganisms were correlated with the severity of nasolacrimal duct (NLD) obstruction observed during surgical intervention. The success rates of probing and silastic intubation as a primary procedure for each identifiable microorganism were documented. Statistical analysis was conducted to correlate the type of microorganism with the tightness of CNLDO and treatment failure. Out of 181 specimens, 22 had no growth (12.1%). LDS with positive culture had 76.6% successful probing (n = 49) and 82.1% successful silastic intubation (n = 78). Gram-positive and Gram-negative species were almost equally detected. The most prevalent organisms were Streptococcus pneumoniae and Hemophilus influenzae (48.1% and 39.2%, respectively). Tight CNLDO was more prevalent in Serratia marcescens (n = 2; 100%) and Staphylococcus aureus (n = 4; 33.3%) infections with a 7.75 Odds ratio [95% confidence interval (CI), 1.67-34.63]. Staphylococcus aureus had 37.5% successful probing; however, success was achieved in all cases with silastic intubation. Serratia marcescens infections had 100% successful silastic intubation. Microbiology study can predict tight CNLDO and helps in choosing the most successful treatment option. CNLDO with Staphylococcus infection and Serratia marcescens were likely to have tight NLD obstruction and silastic intubation had better outcomes.


Sites of biosynthesis, distribution and phloem transport of 3-isobutyl-2-Methoxypyrazine in Capsicum annuum (bell pepper) plants.
The distribution and translocation as well as the biosynthetic sites of 3-isobutyl-2-methoxypyrazine (IBMP) in bell pepper plants (Capsicum annuum) were examined. For IBMP-quantification, a stable-isotope dilution assay (SIDA) was developed, using headspace solid-phase microextraction (HS-SPME) combined with gas chromatography and time-of-flight mass spectrometry (ToF-MS). While IBMP was the most abundant MP in all aerial plant parts, IPMP was dominating in root tissues. The highest IBMP-levels were found in unripe bell pepper fruits. Moreover, feeding experiments with [2H10]-l-leucine revealed that IBMP is biosynthesized in all plant parts, while in roots and ripe bell pepper fruit tissues no incorporation of the labelled precursor was detectable. A potential phloem translocation of IBMP could not be detected.


Pellet gun injury as a source of ocular trauma; a retrospective review of one hundred and eleven cases.
To report the demographic data, treatment methods, and outcomes among patients with pellet gun eye injuries. This study was a retrospective review of all pellet gun eye injuries coming to Farabi Eye Hospital, a referral ocular trauma center in Iran, from February 2009 to November 2013. Patients' demographics, type of injury, choice of management, complications, and post-treatment visual acuity were recorded. One hundred eleven patients with a mean age of 25.7 ± 15.6 years entered the study. The most common age group was younger adults (16-45 years old) (61.3%). The mean uncorrected visual acuity after treatment was 2.05 (20/2240) ±1.5 logMAR. The most prevalent ocular zone was zone III (38.7%), and an intraocular foreign body was present in 97 patients (87.4%). Lid laceration and periocular tissue damage were present in 27 patients (24.3%). Lensectomy and vitrectomy were the most common treatment (31.5%). In most patients (87.4%), the injury was non-deliberate, and the most common time of hospitalization was the same day (45.0%). The only statistically significant indicator of post-treatment visual acuity was ocular trauma score (OTS) at admission (P < 0.001). At the end of follow-up, enucleation was performed for 20 patients (18%), and thirty-six patients (32%) had no light perception (NLP) in vision. Pellet gun injuries were more common among young male patients, and the only statistically significant indicator of post-treatment visual acuity was OTS at admission.


Electron beam induced degradation of indomethacin in aqueous solution: kinetics, degradation mechanism, and toxicity assessment.
Pharmaceutical compounds were emerging contaminants, and the accumulation of pharmaceutical compounds in the environment increased the risk to humans and ecosystems. In this study, electron beam irradiation was applied to degrade indomethacin (IDM) in aqueous solution. IDM degradation followed pseudo-first-order kinetics and 300 μM IDM could be completely degraded at only 2 kGy. According to the quenching experiment, the dose constant ratios of oxidative radicals (•OH) and reductive radicals (e-aq and •H) could be calculated as k•OH: ke aq and •H=4.79:1. As the concentration of H2O2 increased from 0 to 10 mM, the dose constant increased from 1.883 to 2.582 kGy-1. However, degradation effect would be restrained in the existence of NO-3, NO-2, CO2-3, HCO-3, SO2-, and humic acid due to their competition for the active species. Theoretical calculation revealed the radical attacking sites of IDM molecule and the most probable pathways were proposed with identification of intermediates. The attack of •OH mainly resulted in the cleavage of amide bond, indole ring opening, demethoxylation, and •OH addition. Dechlorination and the reduction of the carbonyl group occurred on IDM molecular through the reduction of e-aq and •H. The intermediates could continue to be degraded to small molecule acid, such as formic acid, acetic acid, and oxalic acid. Furthermore, highly toxic IDM transformed into less toxic products during the irradiation process.


Tricuspid reoperation after left-sided rheumatic valve operations.
The management of late tricuspid regurgitation after left-sided valve operations in rheumatic patients remains controversial. The aim of this study was to analyze clinical and echocardiographic outcomes of tricuspid valve procedures after left-sided valve operations in rheumatic patients. This study enrolled 106 rheumatic patients with a history of left-sided valve operations who were undergoing tricuspid valve procedures (53 replacements, 53 repairs). Follow-up was 97% complete, with a mean follow-up of 62 ± 42 months. Clinical and echocardiographic data were analyzed. The early mortality rate was 1.9% (2 of 106 patients). There was no significant difference in cumulative survival at 10 years between patients who underwent tricuspid valve replacement (63.1% ± 13.2%) or repair (80.7% ± 0.8%, p = 0.317). Multivariable Cox regression analysis revealed that old age (hazard ratio [HR], 6.5; p = 0.007), anemia (HR, 10.9; p = 0.004), and left ventricular ejection fraction of less than 0.4 (HR, 10.3; p = 0.001) were predictors of major adverse cardiac events. Among patients who underwent tricuspid valve repair, multivariate analysis revealed that the aortic transprosthetic mean pressure gradient at late follow-up was an independent predictor of late tricuspid regurgitation. Tricuspid valve procedures after left-sided valve operations in rheumatic patients can be performed at low risk with good clinical outcomes. For improved clinical outcomes, early surgical intervention should be considered before the development of anemia and left ventricular dysfunction. A lower aortic transprosthetic mean pressure gradient may help prevent late progression of tricuspid regurgitation in a clinical setting.


Quantitative affinity measurement of small molecule ligand binding to major histocompatibility complex class-I-related protein 1 MR1.
The Major Histocompatibility Complex class I-related protein 1 (MR1) presents small molecule metabolites, drugs, and drug-like molecules that are recognized by MR1-reactive T cells. While we have an understanding of how antigens bind to MR1 and upregulate MR1 cell surface expression, a quantitative, cell-free, assessment of MR1 ligand-binding affinity was lacking. Here, we developed a fluorescence polarization-based assay in which fluorescent MR1 ligand was loaded into MR1 protein in vitro and competitively displaced by candidate ligands over a range of concentrations. Using this assay, ligand affinity for MR1 could be differentiated as strong (IC50 < 1 μM), moderate (1 μM < IC50 < 100 μM), and weak (IC50 > 100 μM). We demonstrated a clear correlation between ligand-binding affinity for MR1, the presence of a covalent bond between MR1 and ligand, and the number of salt bridge and hydrogen bonds formed between MR1 and ligand. Using this newly developed fluorescence polarization-based assay to screen for candidate ligands, we identified the dietary molecules vanillin and ethylvanillin as weak bona fide MR1 ligands. Both upregulated MR1 on the surface of C1R.MR1 cells and the crystal structure of a MAIT cell T cell receptor-MR1-ethylvanillin complex revealed that ethylvanillin formed a Schiff base with K43 of MR1 and was buried within the A'-pocket. Collectively, we developed and validated a method to quantitate the binding affinities of ligands for MR1 that will enable an efficient and rapid screening of candidate MR1 ligands.


A gel-free proteomic-based method for the characterization of Bordetella pertussis clinical isolates.
Bordetella pertussis (Bp) is the etiologic agent of pertussis or whooping cough, a highly contagious respiratory disease occurring primarily in infants and young children. Although vaccine preventable, pertussis cases have increased over the years leading researchers to re-evaluate vaccine control strategies. Since bacterial outer membrane proteins, comprising the surfaceome, often play roles in pathogenesis and antibody-mediated immunity, three recent Bp circulating isolates were examined using proteomics to identify any potential changes in surface protein expression. Fractions enriched for outer membrane proteins were digested with trypsin and the peptides analyzed by nano liquid chromatography-electrospray ionization-mass spectrometry (nLC-ESI-MS), followed by database analysis to elucidate the surfaceomes of our three Bp isolates. Furthermore, a less labor intensive non-gel based antibody affinity capture technology in conjunction with MS was employed to assess each Bp strains' immunogenic outer membrane proteins. This novel technique is generally applicable allowing for the identification of immunogenic surface expressed proteins on pertussis and other pathogenic bacteria.


[Rectal prolapse revealing a tumor: The role of abdominal ultrasound].
Rectal prolapse is rare in children and usually benign. However, there are various diseases that can be associated with it, such as cystic fibrosis or other causes of increased abdominal pressure. Here, we review the various underlying conditions that pediatricians or pediatric gastroenterologists should consider in the case of rectal prolapse. We report on three cases of children with a rectal prolapse and intra-abdominal tumors. Current recommendations and practice do not include a systematic check via abdominal imaging in cases of rectal prolapse. However, in some situations, imaging is indicated to detect a possible expansive process. Thus, in the presence of recurrent prolapse or of associated urinary or neurological signs, imaging is justified so as to allow for an early diagnosis and treatment of these neoplasms. Given its lack of radiation exposure and good sensitivity in children, ultrasound imaging is the first choice.


Urethral diverticulum in a female child.
A urethral diverticulum in a female arises from the wall of the urethra and consists mainly of fibrous tissue lined with epithelium. It is uncommon, and usually presents between decades 3 and 5. Most patients present with non-specific, refractory, lower urinary tract symptoms, unrelated to the diverticulum size or number. The diverticulum may also present as a mass at the introitus. We report a case of urethral diverticulum in a female child that presented as an introital mass.


Results of a double-blind, placebo-controlled, fixed-dose assessment of once-daily OROS® hydromorphone ER in patients with moderate to severe pain associated with chronic osteoarthritis.
Opioids are recommended for patients with moderate to severe pain due to osteoarthritis (OA), who do not receive adequate analgesia from nonopioid treatment. The objective of this study was to evaluate the efficacy and safety of OROS hydromorphone extended-release (ER) compared with placebo in patients with moderate to severe pain associated with OA. This was a randomized, placebo-controlled, double-blind, fixed-dose study. Patients received placebo or fixed-dose OROS hydromorphone ER (8 or 16 mg). The primary efficacy measure was pain intensity score (11-point Numeric Rating Scale) at Maintenance Week 12, analyzed with baseline observation carried forward (BOCF) imputation for missing data. This study did not meet the primary efficacy measure using the BOCF imputation. Study discontinuation was high (52%). When analyzed using last observation carried forward (LOCF) imputation, the prespecified alternate method, OROS hydromorphone ER 16 mg provided significantly better analgesia than placebo (P = 0.0009). Treatment was associated with significant improvements in patient global assessment (P = 0.01), the overall Western Ontario and McMaster Osteoarthritis Index (WOMAC) (P = 0.0003), and its subscales: pain (P = 0.0001), stiffness (P = 0.0023), and physical function (P = 0.0006). Gastrointestinal adverse events, such as constipation and nausea, were common among patients receiving OROS hydromorphone ER. OROS hydromorphone ER failed to achieve statistical significance for the primary endpoint using the prespecified imputation method (BOCF), likely due to the high discontinuation rate associated with the fixed-dose design. When data were analyzed according to an alternate method of imputation (LOCF), OROS hydromorphone ER demonstrated statistically significant improvements in pain, stiffness, and physical function.


Conservative management or gamma knife radiosurgery for vestibular schwannoma: tumor growth, symptoms, and quality of life.
There are few reports about the course of vestibular schwannoma (VS) patients following gamma knife radiosurgery (GKRS) compared with the course following conservative management (CM). In this study, we present prospectively collected data of 237 patients with unilateral VS extending outside the internal acoustic canal who received either GKRS (113) or CM (124). The aim was to measure the effect of GKRS compared with the natural course on tumor growth rate and hearing loss. Secondary end points were postinclusion additional treatment, quality of life (QoL), and symptom development. The patients underwent magnetic resonance imaging scans, clinical examination, and QoL assessment by SF-36 questionnaire. Statistics were performed by using Spearman correlation coefficient, Kaplan-Meier plot, Poisson regression model, mixed linear regression models, and mixed logistic regression models. Mean follow-up time was 55.0 months (26.1 standard deviation, range 10-132). Thirteen patients were lost to follow-up. Serviceable hearing was lost in 54 of 71 (76%) (CM) and 34 of 53 (64%) (GKRS) patients during the study period (not significant, log-rank test). There was a significant reduction in tumor volume over time in the GKRS group. The need for treatment following initial GKRS or CM differed at highly significant levels (log-rank test, P < .001). Symptom and QoL development did not differ significantly between the groups. In VS patients, GKRS reduces the tumor growth rate and thereby the incidence rate of new treatment about tenfold. Hearing is lost at similar rates in both groups. Symptoms and QoL seem not to be significantly affected by GKRS.


Influence of DDT, DDVP and malathion on FSH, LH and testosterone serum levels and testosterone concentration in testis.
Groups of adult male rats were treated with DDT, DDVP or malathion orally for two or three weeks. Body weight and testis weight did not change. FSH and LH levels in serum also remained unchanged, whereas that of testosterone was decreased by DDT. This substance also diminished the concentration of testosterone in the testis. Therefore, the previously observed damage to spermatogenesis by DDT are assumed to be caused by a lack of androgens. Those following treatment with DDVP or malathion seem to be due to a direct cytotoxic effect.


Loss of progranulin function in frontotemporal lobar degeneration.
Frontotemporal lobar degeneration (FTLD) represents a collection of neurodegenerative diseases of frontal and temporal brain regions. It has long been associated with mutations in microtubule-associated protein tau (MAPT), and more recently with loss-of-function mutations in progranulin (PGRN). Phenotypes of PGRN and MAPT mutation carriers overlap, although disease onset in PGRN carriers is a decade later. Mutations in PGRN might influence susceptibility to a wider range of neurodegenerative diseases including Alzheimer and Parkinson diseases. The recent demonstration that mutations in PGRN result in FTLD provided a novel entrance point to the molecular mechanisms leading to this disorder. The high variability in onset age and age-dependent penetrance suggests that the PGRN pathway is highly susceptible to modulating factors that might be exploited to delay the disease processes.


On structures.
Some of the metapsychology involving the concept of structure is briefly reviewed, together with some difficulties presented by it. The concept of structure is defined, for purposes of the paper, and various kinds of structures are delineated. The author confines herself to the "microstructures," such as memories, cognitive structures, affect structures, defenses, identifications. Possible factors related to the development and maintenance of structures are discussed. In addition, the concept of structural change is taken up. It is suggested that an essential in such change is conscious review, however brief. The author proposes that structure formation and change is a fruitful area for mutual work by psychoanalysts and basic scientists.


[Diverticular disease - new insights into pathogenesis].
Diverticular disease is associated with a high incidence, morbidity and burden of the healthcare system. However, the pathogenesis is not yet satisfactorily clarified and thought to be multifactorial. Non-influenceable risk factors include increasing age, genetic predisposition and rare congenital connective tissue diseases. Influenceable risk factors are low-fiber diet, increased meat consumption and obesity. Alterations of connective tissue lead to a weakening of preformed emergence sites of diverticula ("loci minoris resistentiae") and may explain the increased incidence of diverticular disease in diseases caused by a systematic connective tissue disorder. The impact of neuromuscular alterations and disturbed colonic motility on triggering diverticula formation has been previously underestimated. Moreover, intestinal innervation disorders are considered to be responsable for persisting recurrent pain symptoms in chronic diverticular disease.


Second trimester pregnancy termination using extra-amniotic ethacridine lactate.
To investigate the efficacy of ethacridine lactate by the extra-amniotic route for second trimester pregnancy termination and its associated complications. Retrospective study of women undergoing second trimester termination, over 3 1/2 years, with extra-amniotic ethacridine alone, or extra-amniotic ethacridine supplemented later by extra-amniotic 15-methyl prostaglandin F2 alpha. Teaching hospital in Bombay. 315 consecutive women undergoing late abortions with extra-amniotic ethacridine. Demographic features were similar in the two groups. In group 1, 207 women had 150 ml of 0.1% ethacridine lactate injected slowly into the extra-amniotic space. In group 2, 108 women had the initial injection supplemented 6 h later by an extra-amniotic injection of 250 micrograms (1 ml) of 15-methyl prostaglandin F2 alpha. The occurrence of abortion following the induction procedure. The development of complications such as haemorrhage, infection, or injury to the uterus or cervix. The method was successful in 191 women (92%) in group 1 and in 106 (98%) in group 2. The median induction-abortion intervals were 35 and 19 h, respectively (Mann-Whitney U test, P less than 0.001). The corrected complication rate was less than 10% (30 women), with unplanned uterine evacuation in 6% (20), haemorrhage in 1% (4), and pelvic infection in 4% (14). The use of extra-amniotic ethacridine lactate provides an effective and safe treatment method for second trimester legal abortion. The induction-abortion interval can be appreciably reduced by supplementary prostaglandin.


Functional variations in liver tissue during the implantation process of metastatic tumour cells.
We have examined several properties of sinusoidal cells in the unaffected tissue of micrometastasis-containing livers. Tumour cells from either B16 melanoma (B16F10) or Lewis lung carcinoma (LLC) were injected intrasplenically in syngeneic mice and sacrificed on the 7th day. Light and scanning electron microscopy (SEM) showed tumour cells in hepatic veins and sinusoids in close contact with endothelial walls and macrophages. Following quantitative analysis of SEM images from sinusoidal walls it was found that endothelial fenestrae from B16F10 or LLC-colonized livers were diffusely reduced both in size and density/microns 2 throughout the sinusoid wall, although especially affected zone 3 segments. Following the intrasplenic injection of 1 microns fluorescent latex particles 1 h prior to sacrifice of the mice a significant reduction of the latex particle uptake by sinusoidal cells was detected in B16F10-colonized livers (27% of controls) which was in contrast to the significant increase in LLC-colonized mice (180% of controls). Despite the focal character of the tumour cell implantation process, hepatic sinusoidal cells reacted diffusely to metastatic cells. However, over liver acini, endothelial cell changes were mainly expressed in zone 3 while phagocytic properties mainly varied in zone 1 and depending on the tumour type. Although the significance of these sinusoidal changes on metastatic development is unclear, data suggests that "soil" conditions in the liver are different before and after being metastasized by tumour cells.


Performance evaluation of the microINR® point-of-care INR-testing system.
Point-of-care International Normalised Ratio (INR) testing is used frequently. We evaluated the microINR® POC system for accuracy, precision and measurement repeatability, and investigated instrument and test chip variability and error rates. Venous blood INRs of 210 patients on warfarin were obtained with Thromborel® S on the Sysmex CS-2100i® analyser and compared with capillary blood microINR® values. Precision was assessed using control materials. Measurement repeatability was calculated on 51 duplicate finger-prick INRs. Triplicate finger-prick INRs using three different instruments (30 patients) and three different test chip lots (29 patients) were used to evaluate instrument and test chip variability. Linear regression analysis of microINR® and Sysmex CS2100i® values showed a correlation coefficient of 0.96 (P < .0001) and a positive proportional bias of 4.4%. Dosage concordance was 93.8% and clinical agreement 95.7%. All acceptance criteria based on ISO standard 17593:2007 system accuracy requirements were met. Control material coefficients of variation (CV) varied from 6.2% to 16.7%. The capillary blood measurement repeatability CV was 7.5%. No significant instrument (P = .93) or test chip (P = .81) variability was found, and the error rate was low (2.8%). The microINR® instrument is accurate and precise for monitoring warfarin therapy.


Antigenic cross-reactions between Mycoplasma arthritidis and rat tissues.
An antigenic relationship between Mycoplasma arthritidis and rat tissues could be demonstrated using the enzyme-immune assay and the agar gel double diffusion test. Cross-reactions were observed with joint homogenates as well as with muscle, lung, liver, kidney, spleen and brain tissue from rats. In addition, antibodies against joint homogenate were found in the sera of rats infected with M. arthritidis ISR 1 using the indirect hemagglutination test. The significance of common antigens between M. arthritidis and rat tissues for the pathogenesis of the M. arthritidis polyarthritis in rats is discussed.


Effectiveness of Bone Graft for an Alveolar Defect on Adjacent Second Molar After Impacted Mandibular Third Molar Extraction.
This retrospective study examined distal bone healing on the adjacent second molar between the demineralized bone matrix incorporated with recombinant human bone morphogenetic protein-2 (DBM/rhBMP-2) and a collagen sponge in the mandibular third molar extraction socket. From 2018 to 2020, 26 extraction patients (male, average 21.5 years), who received a graft (each of 13 using DBM/rhBMP-2 and collagen plug, respectively) on the extraction socket without primary closure, were enrolled in this study. The bony defect was measured by computed tomography before and 6 months after the extraction. The difference in the bone healing was analyzed between the DBM/rhBMP-2 and collagen plug groups using a Mann-Whitney U test. No complications, such as infection and food packing, were encountered. The DBM/rhBMP-2 and collagen plug groups showed a similar distribution of preoperative bony defect (median 5.8 and 5.0 mm, respectively). After 6 months, more bone healing was observed in the DBM/rhBMP-2 group than in the collagen plug group (median 3.85 and 2.37 mm, respectively, P = .029) CONCLUSIONS: A DBM/rhBMP-2 graft after a third molar extraction does significantly alter the bony defect on the distal aspect of the second molar compared with a collagen plug.


Use of Powder PEG-3350 as a Sole Bowel Preparation: Clinical Case Series of 245 Patients.
To assess the efficacy of low-volume powder polyethylene glycol (PEG)-3350 as a sole bowel preparation for colonoscopy. This case series examined 245 consecutive patients (a mixture of inpatients and outpatients undergoing screening colonoscopy) at a hospital endoscopy center over a 2-year period. The patients received powder PEG-3350 in the amount of 204 g dissolved in 32 oz of water and taken in 3 divided doses 1 hour apart with 8 oz of water in between each dose. Colon preparation scores (CPS) were used to assess the quality of colon cleansing. The results obtained from the 245 patients were collated and compared to those of patients receiving sodium phosphate, the historical control. The mean CPS was calculated to be 3.43, with a standard deviation of 1.12. Of the 245 patients, 92 were scored with a grade of 4, and 5 patients had incomplete colonoscopies secondary to failure of bowel preparation (CPS=0). Among the remaining patients, 22 and 26 were graded as poor (CPS=1) or fair (CPS=2) bowel preparations, respectively. The low-volume powder PEG-3350 formula used in our case series showed effective colon cleansing and may be considered for use as a sole bowel preparation.


What is the relationship between alexithymia and experiential avoidance? A latent analysis using three alexithymia questionnaires.
Alexithymia is a clinically relevant personality trait characterized by poor emotional awareness and associated with several psychological and physical health concerns. Individuals with high alexithymia tend to engage in experiential avoidance and this may mediate psychological distress. However, little is known about what specific processes of experiential avoidance are involved, and the nature of the relation between alexithymia, experiential avoidance, and psychological distress remains unclear at a latent construct level. To examine this relationship at the latent construct level, a representative sample of 693 U.S. adults completed alexithymia (TAS-20, BVAQ, PAQ), general distress (DASS-21), multi-dimensional experiential avoidance (MEAQ), and general health (PROMIS-G-10) questionnaires. Structural equation modeling revealed that alexithymia significantly predicted experiential avoidance (β = 0.966, t = 82.383, p < .01), experiential avoidance significantly predicted general distress (β = 0.810, t = 2.017, p < .05), and experiential avoidance fully mediated the relationship between alexithymia and general distress (βindirect = -0.159, t = -0.398, p > .05). Correlations between alexithymia and experiential avoidance subfactors revealed a strong relationship to the repression and denial subfactor. Experiential avoidance is a promising target for clinical interventions, though longitudinal research is necessary to elucidate how the relationship between alexithymia and experiential avoidance unfolds over time.


Falsely decreased HbA1c in a type 2 diabetic patient treated with dapsone.
Glycated hemoglobin A1c (HbA1c) is an important indicator of glycemic control. The current recommendation for glycemic control based on HbA1c values has been widely accepted. However, HbA1c values depend on the lifespan of erythrocytes and the assay methods used. Here, we report the case of a patient with type 2 diabetes with unusual falling of HbA1c due to interference from dapsone treatment for leukocytoclastic vasculitis. He was a 52-year-old man, who was diagnosed with type 2 diabetes mellitus 5 years previously and who had been treated in our hospital in the past 3 years. Glycemia was controlled by sulfonylurea and metformin. During the 3-years follow-up period, HbA1c dropped significantly during the addition of dapsone treatment, although plasma glucose levels remained stable. HbA1c levels were raised after discontinuation of dapsone. With rechallenge of dapsone usage, HbA1c decreased again. We conclude that dapsone may be the cause of artificially low HbA1c. Other measurements to monitor glycemic control should be considered when dapsone is used for the treatment of concurrent disorders, such as autoimmune disease and pneumocystis jiroveci pneumonia.


Transmission of equine influenza virus to English foxhounds.
We retrospectively demonstrated that an outbreak of severe respiratory disease in a pack of English foxhounds in the United Kingdom in September 2002 was caused by an equine influenza A virus (H3N8). We also demonstrated that canine respiratory tissue possesses the relevant receptors for infection with equine influenza virus.


The clinical use of platelet scintigraphy with 111-In-oxine.
Platelet scintigraphy was performed on 62 patients with cerebral ischaemia. Pathological scintigraphic images were obtained in 29 of the 62 patients. In 79.3% of these 29 patients the scan was abnormal in the vessel clinically affected. Platelet scintigraphy was abnormal in 21 of 34 patients with normal angiogram or only slight atherosclerosis. In patients undergoing antiplatelet therapy, platelet scintigraphy was less often positive than in untreated patients. It is suggested that platelet scintigraphy could be an appropriate technique for detecting small mural thrombi of the carotid artery, which are the source of arterio-arterial emboli, and for controlling the efficiency of antiplatelet therapy.


Positive Effects of Local Botulinum Toxin Injection and Colchicine for Complicated Chronic Recurrent Parotitis: A Case Report.
Chronic recurrent parotitis (CRP) is a rare affliction of unknown cause characterized by recurrent episodes of unilateral or bilateral nonobstructive and nonsuppurative inflammation of the parotid glands. Management of CRP is not standardized, and attempts at treatment often fail. We report a case of a 29-year-old female patient with CRP for 13 years, with recurrent acute episodes, complicated with a collection and cutaneous fistula, refractory to repeated courses of corticosteroids and antibiotics. Injections of botulinum toxin in the parotid gland and maintenance treatment with oral colchicine lead to a rapid and sustained improvement. Local botulinum toxin injections associated with colchicine might represent a safe and noninvasive treatment of CRP. The possible beneficial effect of colchicine could be an argument for auto-inflammatory participation in the pathogenesis of CRP.


Deep computational pathology in breast cancer.
Deep Learning (DL) algorithms are a set of techniques that exploit large and/or complex real-world datasets for cross-domain and cross-discipline prediction and classification tasks. DL architectures excel in computer vision tasks, and in particular image processing and interpretation. This has prompted a wave of disruptingly innovative applications in medical imaging, where DL strategies have the potential to vastly outperform human experts. This is particularly relevant in the context of histopathology, where whole slide imaging (WSI) of stained tissue in conjuction with DL algorithms for their interpretation, selection and cancer staging are beginning to play an ever increasing role in supporting human operators in visual assessments. This has the potential to reduce everyday workload as well as to increase precision and reproducibility across observers, centers, staining techniques and even pathologies. In this paper we introduce the most common DL architectures used in image analysis, with a focus on histopathological image analysis in general and in breast histology in particular. We briefly review how, state-of-art DL architectures compare to human performance on across a number of critical tasks such as mitotic count, tubules analysis and nuclear pleomorphism analysis. Also, the development of DL algorithms specialized to pathology images have been enormously fueled by a number of world-wide challenges based on large, multicentric image databases which are now publicly available. In turn, this has allowed most recent efforts to shift more and more towards semi-supervised learning methods, which provide greater flexibility and applicability. We also review all major repositories of manually labelled pathology images in breast cancer and provide an in-depth discussion of the challenges specific to training DL architectures to interpret WSI data, as well as a review of the state-of-the-art methods for interpretation of images generated from immunohistochemical analysis of breast lesions. We finally discuss the future challenges and opportunities which the adoption of DL paradigms is most likely to pose in the field of pathology for breast cancer detection, diagnosis, staging and prognosis. This review is intended as a comprehensive stepping stone into the field of modern computational pathology for a transdisciplinary readership across technical and medical disciplines.


Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: proposal for a new dosing regimen.
Warfarin is one of the most widely used anticoagulants, yet interindividual differences in drug response, a narrow therapeutic range and a high risk of bleeding or stroke complicate its use. We aimed to determine the allele and genotype frequency of VKORC1 1173 C>T, CYP2C9*2 and CYP2C9*3 variant polymorphisms in the Egyptian population and to evaluate their influence on the interindividual differences in warfarin dosage. A total of 154 unrelated healthy adult patients and 46 warfarin-treated patients were included. SYBR Green-based real-time polymerase chain reaction (PCR) assay was used for studying VKORC1 (C1173T) and CYP2C9*3 polymorphisms. Mutagenically separated PCR assay was used to detect the CYP2C9*2 allele. VKORC1 genotype frequencies were 11%, 24% and 65% for CC, CT and TT, respectively. The prevalence of CYP2C9 haplotypes was 81% (*1\*1), 3.3% (*1\*2), 9.7% (*1\*3), 4.5% (*2\*2) and 0.65% (2\*3 and *3\*3). VKORC1 TT and CYP2C9*2\*2 were associated with a significantly lower warfarin dose. VKORC1 and CYP2C9 accounted for 31.7% and 15.6% of warfarin dose variability, respectively, and together with clinical factors explained 61.3% of total variability. VKORC1-TT and CYP2C9 *1/*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.


Inositol trisphosphate does not release Ca2+ from permeabilized cardiac myocytes and sarcoplasmic reticulum.
The possibility that inositol 1,4,5-trisphosphate (IP3) may act as a Ca2+-mobilizing second messenger in cardiac muscle in a manner analogous to its actions in other cell types has been examined using saponin-permeabilized myocytes and isolated cardiac sarcoplasmic reticulum. Myocytes permeabilized in the presence of MgATP2- sequestered Ca2+ to a level of about 200 nM, similar to the cytosolic free Ca2+ concentration of intact cells, but addition of IP3 was ineffective in causing Ca2+ release from intracellular stores. Similarly, IP3 (up to 50 microM) was unable to inhibit Ca2+ uptake or cause Ca2+ release from isolated canine cardiac sarcoplasmic reticulum vesicles in the presence of either EGTA or sodium vanadate. These results indicate that IP3 is unlikely to mediate mobilization of intracellular Ca2+ stores in myocardial cells.


Infrared spectroscopy of supported lipid monolayer, bilayer, and multibilayer membranes.
Cecropin A was examined in supported monolayer, bilayer, and multibilayer lipid membranes using attenuated total internal reflection Fourier-transform infrared spectroscopy. The spectral features provide an abundance of information about the conformation and orientation of the peptide, as well as about the effects of the peptide on lipid order. In this case, they serve to contrast results from the three preparations. The results of monolayer and bilayer studies are generally similar, although differences in the nature of the membranes appear to cause minor changes in the conformation and orientation of the peptide. The results of the multibilayer studies are different in many respects from those of the monolayer and bilayer studies, suggesting that fundamentally different peptide-lipid interactions occur in multibilayers.


Considerations and treatment of direct and indirect pulp-capping.
Depending on the clinical setting, vital pulp therapy can be managed with an indirect or direct pulp-capping procedure. The determination of which therapy to employ is a decision that must be made by the clinician at the time of treatment. It is hoped that the preceding discussion has informed the clinician as to both the indications and contraindications for each type of treatment and the rationale for selection. Because every possible clinical situation cannot be presented, it is anticipated that by understanding the principles presented in this article, the clinician will be able to correctly identify which therapeutic modality will most benefit the patient. Table 1 is presented as a quick reference to aid in selecting appropriate candidates for pulp-capping procedures.


Cytoskeletal and scaffolding proteins as structural and functional determinants of TRP channels.
Transient receptor potential (TRP) channels are six transmembrane-spanning proteins, with variable selectivity for cations, that play a relevant role in intracellular Ca(2+) homeostasis. There is a large body of evidence that shows association of TRP channels with the actin cytoskeleton or even the microtubules and demonstrating the functional importance of this interaction for TRP channel function. Conversely, cation currents through TRP channels have also been found to modulate cytoskeleton rearrangements. The interplay between TRP channels and the cytoskeleton has been demonstrated to be essential for full activation of a variety of cellular functions. Furthermore, TRP channels have been reported to take part of macromolecular complexes including different signal transduction proteins. Scaffolding proteins play a relevant role in the association of TRP proteins with other signaling molecules into specific microdomains. Especially relevant are the roles of the Homer family members for the regulation of TRPC channel gating in mammals and INAD in the modulation of Drosophila TRP channels. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.


The management of congenital adrenal hyperplasia during preconception, pregnancy, and postpartum.
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of steroidogenesis of the adrenal cortex, most commonly due to 21-hydroxylase deficiency caused by mutations in the CYP21A2 gene. Although women with CAH have decreased fecundity, they are able to conceive; thus, if pregnancy is not desired, contraception options should be offered. If fertility is desired, women with classic CAH should first optimize glucocorticoid treatment, followed by ovulation induction medications and gonadotropins if needed. Due to the possible pregnancy complications and implications on the offspring, preconception genetic testing and counseling with a high-risk obstetrics specialist is recommended. For couples trying to avoid having a child with CAH, care with a reproductive endocrinology and infertility specialist to utilize in vitro fertilization can be offered, with or without preimplantation genetic testing for monogenic disorders. Prenatal screening and diagnosis options during pregnancy include maternal serum cell free-DNA for sex of the baby, and chorionic villus sampling and amniocentesis for diagnosis of CAH. Pregnant women with classic CAH need glucocorticoids to be adjusted during the pregnancy, at the time of delivery, and postpartum, and should be monitored for adrenal crisis. Maternal and fetal risks may include chorioamnionitis, maternal hypertension, gestational diabetes, cesarean section, and small for gestational age infants. This review on CAH due to 21-hydroxylase deficiency highlights reproductive health including genetic transmission, contraception options, glucocorticoid management, fertility treatments, as well as testing, antenatal monitoring, and management during pregnancy, delivery, and postpartum.


Immediate reactions to patch tests with balsam of Peru.
Closed patch tests with balsam of Peru gave rise to nine immediate reactions among 121 patients with different dermatoses and to 10 reactions among 57 patients with chronic urticaria. Among compounds of balsam of Peru, cinnamic aldehyde, cinnamic acid benzoic acid and benzaldehyde also gave the same reactions. The reactions could not passively be transferred with serum from patients. They were abolished by antihistamine given before testing, and by pretreatment with compound 48/80. Balsam of Peru and cinnamic aldehyde did not provoke new symptoms when given orally to patients.


[The influence of hysterical symptoms on the comorbid mental disorders].
to investigate the influence of conversion-dissociative (hysterical) disorder on comorbid mental disorders. Authors examined 154 inpatients with conversion-dissociative disorder with comorbid mental pathology. Conversion-dissociative hysterical symptoms mask or mimic main clinical manifestations of comorbid mental disorders and facilitate its exacerbations and deterioration.


Transmastoid approach to temporal bone cerebrospinal fluid leaks.
The aim of the study was to evaluate various presentations and treatment options for spontaneous cerebrospinal fluid (CSF) leakage originating in the temporal bone. Clinical data and imaging results for 18 ears (15 patients) presenting with spontaneous CSF leakage originating in the temporal bone were reviewed. Average follow-up period was 13.5 months. The main outcome measure was presence of persistent CSF leak postoperatively. A standard postauricular mastoidectomy was performed. Fifteen patients diagnosed with spontaneous CSF leakage over an 8-year period including 3 treated for bilateral disease were included in the study. The age ranged between 33 and 83 years. Presenting symptoms included serous otitis media (44%), persistent otorrhea after tympanostomy tube placement (28%), and meningitis (28%). Preoperative diagnosis was made using imaging studies and was substantiated by observation of CSF leakage and dural herniation intraoperatively. Treatment was eustachian tube plugging (5%), mastoidectomy with fat obliteration (61%), middle fossa approach with extradural (17%), intradural repair (5%), or combined middle fossa and transmastoid (TM) approach (11%). Successful treatment was obtained in 17 of the 18 cases. The last 9 patients in the series underwent TM approach alone for repair with no treatment failures. Repair of defects in tegmen mastoideum and posterior fossa can be successfully achieved on an outpatient basis without regard to size and multitude of defects via TM approach. This approach obviates the need for a craniotomy or lumbar drain.


Structural racism and the impact on incarcerated midlife women.
High recidivism rates indicate that current forms of imprisonment may be an ineffective response to problems that mainly burden those ensconced in poverty and marginalization. Homelessness, unemployment, racial disparities, drug use, and mental illness, disappear from public view when the afflicted individuals are relegated to a life behind bars. Women are the fastest growing prison population and most incarcerated women are from Black and Latinx groups. Structural racism encompasses the many ways in which society fosters racial discrimination through mutually reinforcing unfair systems of housing, education, employment, earnings, benefits, credit, media, health care, and criminal justice. In turn, this behavior reinforces discriminatory beliefs, values, and distribution of resources. Structural racism pervades every aspect of society, including the carceral system, from policing to prosecutorial decisions, pretrial release processes, sentencing, correctional discipline, and even reentry. Women constitute a minority within the carceral system, and as a result, their unique health care needs, especially during the midlife period, are inadequately addressed and often overlooked. There is also a general lack of gender sensitivity and special considerations in existing jail and prison policies and practices. This commentary highlights the impact of structural racism on the arrests and incarceration of women, and discusses their special health and wellness needs, with emphasis on midlife women. It also illuminates the need to address structural racism and its ripple effects within the carceral system.


A systematic review of single-sample glomerular filtration rate measurement techniques and demonstration of equal accuracy to slope-intercept methods.
We aimed to identify the most accurate single-sample glomerular filtration rate (SS-GFR) technique for all patient ages. We performed a systematic review of all published SS-GFR measurement techniques and compared the results from each test with a gold-standard nine-point 'area-under-curve' measurement of GFR as well as slope-intercept (SI-GFR) methods for 412 GFR tests. We have shown that for patients of all ages the SS-GFR technique developed by Fleming and colleagues delivers the best accuracy and precision, with results equivalent to those calculated by SI-GFR. The median percentage difference from the gold-standard GFR for the Fleming technique is 4.8% (95% confidence interval 3.9-5.7%) and that for the three-point SI-GFR is 5.6% (95% confidence interval 4.9-6.3%). The interquartile range of the distribution of percentage difference from the gold standard is -0.23 to 11% for the Fleming method and 1.6-11% for the three-point SI-GFR. The Fleming technique outperforms the method currently recommended by the international guidelines, and is simpler as only one equation is required for all patients instead of separate equations for adults and children. We propose that the SS-GFR technique of Fleming replace the methods currently recommended by the international and BNMS guidelines for routine measurement of GFR for expected results greater than 30 ml/min/1.73 m. A thorough system of measurement checks should be implemented for all methods of GFR assessment; the perceived lack of opportunity for quality control checks to be performed on the result of a single-sample measurement is addressed in the companion paper of this study.


Phenotypic variability associated to genomic changes in the main vector of Chagas disease in the southern cone of South America.
This study shows for the first time, the relationship between chromosomic and meristic quantitative characters of Triatoma infestans, the main vector of Chagas disease in the southern cone of South America. The antennal phenotype of 225 adults from five countries and three cytotypes, were analyzed using univariate and multivariate techniques. The study found a clear association between cytotypes and antennal phenotypes. The complexity of the antennal sensilla pattern was higher in the non-Andean cytotype, showing more chemoreceptors usually linked to sexual behaviour, host finding and flight. The phenetic differences were more notorious on females than on males. Changes in the sexual dimorphism were detected, being the differences most notorious in the non-Andean cytotype. Similitude of the geographic populations using the antennal phenotype coincides with environmental gradient of the area, showing a close association between the physical features of the living zones and quantitative traits of the vectors. The epidemiological implications of the phenetic differences observed in the study are discussed.


Effects of culture conditions on the synthesis of human chorionic gonadotropin by placental organ cultures.
Culture conditions for maintaining first trimester human placenta in organ culture, which enhance the secretion of human chorionic gonadotropin (hCG), are described. Nutrient medium, oxygen tension and Gelfoam support matrix influence the synthesis of hCG by these cultures. Placental tissue remained viable for the duration of experiments (12 days) as judged by the incorporation of tritiated thymidine into DNA and the lack of release of incorporated [125I]iododeoxyuridine. Optimal conditions for hCG synthesis in placental organ culture included an atmosphere of 95% air and 5% Co2 (approximately 20% O2), CMRL 1066 medium containing fetal human or bovine serum, insulin, hydrocortisone and retinal acetate. Multiple pieces of placenta could be cultured in the same dish with an additive effect on hCG secretion. The functional responsiveness of these placental cultures was demonstrated by modulation of hCG synthesis with theophylline and 3'5' dibutyryl cyclic AMP.


Standardisation of Tinnitus Handicap Inventory in Hindi.
Tinnitus is defined as perception of sound in ear continuously without presence of any external stimuli. It is mainly due to the activity within central nervous system without any mechanical or vibratory activity that stimulates the cochlea. It is purely subjective phenomenon that cannot be measured by the any physical scale. Tinnitus handicap inventory is very useful tool to measure the severity of impact of tinnitus on person's life. There is lack of questionnaire in Hindi and this work will help a lot in future. The English THI was translated to Hindi by person expert in both English and Hindi. The translated THI was given to 40 people with Hindi as mother tongue for rechecking the words. The final THI (Hindi) was used in assessment of severity in 100 tinnitus patient. The observed data was analysed by using Microsoft excel. Reliability of THI Hindi was high (Pearson correlation .98, test and retest method), factor analysis indicated that TH1 Hindi has unified. The THI Hindi version is reliable. THI Hindi can be used to assessment of severity of tinnitus in Hindi speaking population.


Combinatorial chemistry: from peptides and peptidomimetics to small organic and heterocyclic compounds.
Modified dipeptides have been used successfully for the generation of a variety of small organic and heterocyclic combinatorial libraries, including linear urea, polyamine, hydantoin, thiohydantoin, cyclic urea, cyclic thiourea and bicyclic guanidine. The synthesis and screening results for a number of these libraries are described. The solid phase synthesis of heterocyclic compounds such as diazepine and thiomorpholinone are also described.


Adsorption of cationic and anionic surfactants on natural and synthetic carbonate materials.
Adsorption of cationic and anionic surfactants on carbonate materials is investigated in this study. Cetylpyridinium chloride (CPC) and sodium dodecyl sulfate (SDS) are chosen as typical cationic and anionic surfactants, respectively. It is found that the cationic CPC exhibits negligible adsorption on synthetic calcite in deionized water compared with the adsorption of the anionic SDS. However, a substantial amount of adsorption of CPC is observed on natural carbonates, such as dolomite and limestone. X-ray photoelectron spectroscopy (XPS) reveals that that a substantial amount of silicon and aluminum exists in natural dolomite and limestone but not in synthetic calcite. The adsorption plateau of CPC on carbonates highly depends on the silicon composition in the carbonate samples due to the strong electrostatic interaction between CPC and negative binding sites in silica and/or clay. The adsorption of CPC on natural carbonates is reduced in the presence of 1atm CO2 compared with the case under 1atm air, while SDS precipitates out of the solution under 1atm CO2 due to its intolerance to divalent ions released from the carbonate surface as a result of CO2 acidification.


Urokinase receptor surface expression regulates monocyte migration and is associated with accelerated atherosclerosis.
The urokinase receptor (uPAR) is a key regulator of pericellular proteolysis, cell adhesion and migration, all of which are fundamental processes in atherogenesis. We hypothesized that increased monocytic uPAR expression in circulation is associated with the formation and development of atherosclerosis. A total of 42 male apoE-/- mice were ramdonly divided into high-fat (HF) diet and normal diet (n=21 per group). The percentage of uPAR expressing monocytes (PUEM) and the expression of uPAR within different types of atherosclerotic plaques were measured at an interval of 3 weeks from week 10 to week 16. In vitro, uPAR expression upon ox-LDL stimulation and the migration of monocytes were examined. PUEM in circulation was significantly higher in animals with HF diet compared with those having normal diet (p<0.03). The augmented levels of PUEM were associated with body weight, visceral fat weight and numbers of uPAR+macrophages within atherosclerotic lesions. Accumulation of uPAR+macrophages increased with the progression of atherosclerosis. Monocytes upon ox-LDL stimulation exhibited an increased uPAR expression and uPAR antibody markedly suppressed monocyte migration induced by monocyte chemotactic protein-1. uPAR modulated monocyte migration was accelerated by uPA and was suppressed by amino terminal fragment of uPA dependent. Over-expression of uPAR both in circulating monocytes and in atherosclerotic lesions is associated with the development of atherosclerotic plaques. uPAR and its interaction with uPA may contribute to enhanced monocyte migration. Thus, uPAR may be a novel target for prevention of uncontrolled monocyte recruitment in inflammatory atherogenic process.


[Breast reconstruction with Muscle-Sparing Latissimus Dorsi flap combined to a Thoraco-Abdominal advancement flap and fat grafting].
The Latissimus Dorsi flap (or LD flap) was first described by the Tansini in 1896 and published in 1906. It concerned a case of chest wall reconstruction after breast amputation. The use of the LD flap in all its variants is very frequent in breast reconstruction. In these indications, the muscle is harvested for skin paddle vascularization and/or for bringing volume to the reconstructed breast. When all or most of the muscle is taken, its motor function is completely lost. The functional sequelae due to the loss of the latissimus dorsi muscle are then definitive. Tobin et al. showed that the LD muscle can be separated into two flaps based on the division of the thoracodorsal artery; the concept of muscle-sparing was then posed (Muscle-Sparing Latissimus Dorsi [MSLD]). The MSLD as we perform now, concerns only a thin muscle strip and preserves 95% of the LD muscle with its vascularization and motor innervation. This technique is quick with very low donor site morbidity. The functional sequelae and postoperative complications appear limited compared to the harvest of a total LD whatever the posterior scar. The volume of the breast to be reconstructed is obtained by several sessions of fat grafting. We present here the anatomical bases and the surgical technique of the muscle-sparing latissimus dorsi associated with a thoracoabdominal advancement flap and fat grafting in breast reconstruction.


Copper overload in Paracoccidioides lutzii results in the accumulation of ergosterol and melanin.
Paracoccidioidomycosis is a highly prevalent systemic mycosis in Latin America, caused by fungi of the genus Paracoccidioides. Copper is essential for eukaryotes and bacteria. This micronutrient is used in many vital biochemical processes, although metal excess levels can be toxic for organisms. Pathways underlying copper overload are poorly understood in members of the Paracoccidioides complex. The responses of Paracoccidioides lutzii yeast cells to copper overload were here evaluated. The results showed that under copper overload, cells presented a dark brown pigment, identified as melanin. Proteomic analyses identified mainly the accumulation of proteins related to amino acids metabolism, ergosterol synthesis and melanin production, suggesting that P. lutzii responds to copper overload by changing aspects of its metabolism and also plasma membrane and cell wall remodeling. Proteomic data were confirmed by biochemical analysis.


Naturally occurring NS gene variants in an avian influenza virus isolate.
The A/Turkey/Wisconsin/68 (H5N9) isolate of avian influenza (AI) consists of two virus populations which have different NS genes and differ in their biological responses in chicken embryos. They were classified as being either rapidly embryo-lethal (REL) or slowly embryo-lethal (SEL), (Avian Dis., 33 (1989) 695-706). In this study, sequence analysis identified only two nucleotide differences between the two NS genes, creating single amino acid differences in both the NS1 and the NS2 protein. The difference in the NS1 protein appears to be neutral, while the differences in the NS2 places a phenylalanine at position 48. This amino acid has not been previously demonstrated at this position in an NS2 sequence and its presence results in a distinct hydrophobic shift in the region. The sequence specifying the phenylalanine also creates an EcoRI site in the cDNA of the REL NS gene. Analysis of several clones showed that this site appears to co-segregate with the REL characteristic. Molecular differences between the two NS gene variants were reflected by differences in the kinetics of early protein synthesis in infected cells. In particular, the NS2 protein is in higher concentration (relative to the NS1) in SEL-infected cells than in REL-infected cells. No differences were detectable, however, in the rates of viral replication, either in cell culture or in embryos. Also, the REL or SEL rate was established early during infection of the embryo and could not be competed out by the other variant population 3 h after inoculation. Thus, these two natural NS gene variants appear to specify early differences which influence the time of death of an infected embryo but the differences do not appear to influence virus replication.


Erratum: "What respiratory physicians should know about parasomnias". Imran Johan Meurling, Guy Leschziner and Panagis Drakatos. Breathe 2022; 18: 220067.
[This corrects the article DOI: 10.1183/20734735.0067-2022.].


Current Prehabilitation Programs Do Not Improve the Postoperative Outcomes of Patients Scheduled for Lumbar Spine Surgery: A Systematic Review With Meta-analysis.
To assess the effectiveness of prehabilitation in patients with degenerative disorders of the lumbar spine who are scheduled for spine surgery. Intervention systematic review with meta-analysis. Seven electronic databases were systematically searched for randomized controlled trials or propensity-matched cohorts. Studies that measured the effect of prehabilitation interventions (ie, exercise therapy and cognitive behavioral therapy [CBT]) on physical functioning, pain, complications, adverse events related to prehabilitation, health-related quality of life, psychological outcomes, length of hospital stay, use of analgesics, and return to work were included. Data were extracted at baseline (preoperatively) and at short-term (6 weeks or less), medium-term (greater than 6 weeks and up to 6 months), and long-term (greater than 6 months) follow-ups. Pooled effects were analyzed as mean differences and 95% confidence intervals (CIs). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Cognitive behavioral therapy interventions were no more effective than usual care for all outcomes. Pooled effect sizes were -2.0 (95% CI: -4.4, 0.4) for physical functioning, -1.9 (95% CI: -5.2, 1.4) for back pain, and -0.4 (95% CI: -4.1, 0.4) for leg pain. Certainty of evidence for CBT ranged from very low to low. Only 1 study focused on exercise therapy and found a positive effect on short-term outcomes. There was very low-certainty to low-certainty evidence of no additional effect of CBT interventions on outcomes in patients scheduled for lumbar surgery. Existing evidence was too limited to draw conclusions about the effects of exercise therapy. J Orthop Sports Phys Ther 2021;51(3):103-114. Epub 25 Dec 2020. doi:10.2519/jospt.2021.9748.


Cardiac hypertrophic risk markers of left ventricle and left atrium in chronic heart failure due to aortic and mitral valve disease.
Chronic valvular heart disease leads to systolic dysfunction and left atrial enlargement that ultimately results in heart failure. To investigate prognostic importance of Echocardiography and plasma natriuretic peptide levels that increase as a compensatory response and can be used as predictive markers for cardiac hypertrophy. The patients were divided into three groups: 51 with left ventricle hypertrophy due to aortic valve disease; 126 with left atrial enlargement due to mitral valve dysfunction; and 76 with both conditions. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) plasma levels were measured in all three respective groups showing dilated cardiomyopathy. The mean left ventricular end-diastolic dimension at 64.3 ± 1.6 mm (P < 0.00) and left atrial dimension at 58.3 ± 3.7 mm (P < 0.00) were significantly high. However, patients with both conditions showed significantly high values for left ventricular end-diastolic dimension (63.3 ± 3 mm, P < 0.00) and left atrial dimension (54.9 ± 4 mm, P < 0.00) when compared with controls. A significant positive correlation was found between plasma natriuretic peptides levels and dilated cardiomyopathy. The mean values of ANP were 173 ± 46.6 pg/mL (P < 0.00), 140.4 ± 42.4 pg/mL (P < 0.00), and 295.1 ± 67.5 pg/mL (P < 0.00), significantly high in all three respective disease groups. The levels of BNP were also significantly high at 189 ± 44.5 pg/mL (P < 0.00), 166.6 ± 36.6 pg/mL (P < 0.00), and 323 ± 69.1 pg/mL (P < 0.00) in the disease groups with left ventricular hypertrophy, left atrial enlargement, and the disease group showing both characteristics, respectively. Significant positive associations were found between left ventricle hypertrophy and left atrial enlargement with ANP and BNP.


Effect of different doses of aerobic exercise on total white blood cell (WBC) and WBC subfraction number in postmenopausal women: results from DREW.
Elevated total white blood cell (WBC) count is associated with an increased risk of coronary heart disease and death. Aerobic exercise is associated with lower total WBC, neutrophil, and monocyte counts. However, no studies have evaluated the effect of the amount of aerobic exercise (dose) on total WBC and WBC subfraction counts. To examine the effects of 3 different doses of aerobic exercise on changes in total WBC and WBC subfraction counts and independent effects of changes in fitness, adiposity, markers of inflammation (IL-6, TNF-α, C-reactive protein), fasting glucose metabolism, and adiponectin. Data from 390 sedentary, overweight/obese postmenopausal women from the DREW study were used in these analyses. Women were randomized to a non-exercise control group or one of 3 exercise groups: energy expenditure of 4, 8, or 12 kcal kg(-1)⋅week(-1) (KKW) for 6 months at an intensity of 50% VO2peak. A dose-dependent decrease in total WBC counts (trend P = 0.002) was observed with a significant decrease in the 12KKW group (-163.1±140.0 cells/µL; mean±95%CI) compared with the control (138.6±144.7 cells/µL). A similar response was seen in the neutrophil subfraction (trend P = 0.001) with a significant decrease in the 12KKW group (-152.6±115.1 cells/µL) compared with both the control and 4KKW groups (96.4±119.0 and 21.9±95.3 cells/µL, respectively) and in the 8KKW group (-102.4±125.0 cells/µL) compared with the control. When divided into high/low baseline WBC categories (median split), a dose-dependent decrease in both total WBCs (P = 0.003) and neutrophils (P<0.001) was observed in women with high baseline WBC counts. The effects of exercise dose on total WBC and neutrophil counts persisted after accounting for significant independent effects of change in waist circumference and IL-6. Aerobic exercise training reduces total WBC and neutrophil counts, in a dose-dependent manner, in overweight/obese postmenopausal women and is especially beneficial for those with systemic low grade inflammation. NCT00011193.


ER stress is involved in Abeta-induced GSK-3beta activation and tau phosphorylation.
Intracellular neurofibrillary tangles, one of the characteristic hallmarks of Alzheimer's disease (AD), are mainly composed of hyperphosphorylated tau. The abnormal tau phosphorylation seems to be related to altered activity of kinases such as glycogen synthase kinase-3beta (GSK-3beta). Tau pathology is thought to be a later event during the progression of the disease, and it seems to occur as a consequence of amyloid-beta (Abeta) peptide accumulation. The aim of this work was to investigate whether soluble Abeta1-42, particularly oligomers that correspond to the neurotoxic species involved early in the development of AD, triggers tau phosphorylation by a mechanism involving activation of tau-kinase GSK-3beta. Several studies suggest that GSK-3beta plays a central role in signaling the downstream effects of endoplasmic reticulum (ER) stress. Therefore, the involvement of ER Ca(2+) release in GSK-3beta activation and tau phosphorylation induced by Abeta1-42 oligomers was evaluated using dantrolene, an inhibitor of Ca(2+) release through channels associated with ER ryanodine receptors. We observed that Abeta1-42 oligomers increase tau phosphorylation and compromises cell survival through a mechanism mediated by GSK-3beta activation. We also demonstrated that oligomeric Abeta1-42 induces ER stress and that ER Ca(2+) release is involved in oligomer-induced GSK-3beta activation and tau phosphorylation. This work suggests that GSK-3beta can be a promising target for therapeutic intervention in AD.


Eco-friendly silver nanoparticles (AgNPs) fabricated by green synthesis using the crude extract of marine polychaete, Marphysa moribidii: biosynthesis, characterisation, and antibacterial applications.
The non-hazardous silver nanoparticles (AgNPs) synthesised using the extract of a biological organism has gained widespread attention for various applications, mainly in healthcare. This study aimed at synthesising AgNPs using the aqueous extract of Marphysa moribidii (Annelida, Polychaeta) and to evaluate their antibacterial activities. AgNPs were synthesised in response to silver nitrate (AgNO3) with polychaete crude extract for 24 h incubation; the polychaete crude extract acted as both reducing and stabilising agents. The presence of biosynthesised AgNPs was confirmed by an analysis of colour variations from pinkish to yellowish-brown, as well as the appearance of surface Plasmon resonance (SPR) bands at 398-400 nm using ultraviolet-visible spectroscopy. Biosynthesised AgNPs were characterised by dynamic light scattering, scanning electron microscope, transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. Biosynthesised AgNPs showed a significant effect (p < 0.05) on Gram-positive bacteria (Staphylococcus aureus and S . epidermidis) and Gram-negative bacteria (Escherichia coli, Klebsiella pnemoniae, Salmonella typhimurium, Serratia sp., Shigella sonnei, and Pseudomonas aeruginosa). Thus, the crude extract of M. moribidii has a potential as a reducing agent for the development of future nanometal-based antibacterial agent, AgNPs, for the treatment of infectious diseases caused by pathogenic bacteria.


Preoperative assessment of blood supply and its role in predicting anastomotic leak.
Anastomosis leak is one of the significant postoperative complications after colorectal surgery. The aim of this systematic review was to synthesize the evidence relative to the preoperative assessment of the colon and rectum blood supply and to investigate its role in predicting anastomosis leak. This systematic review was conducted according to the recommendations of the Cochrane Handbook for Reviews of Interventions and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Embase, and the Cochrane Library were searched to identify eligible studies. The main outcome variable was the preoperative assessment of patterns of blood supply to the colon and the impact of these patterns on anastomosis leak. The quality of bias control in the studies was assessed using the Newcastle-Ottawa Scale. Due to the heterogeneous nature of the included studies, no meta-analysis was conducted. Fourteen studies were included. The study covered a period from 1978 to 2021. A significant degree of variation in the arterial and/or venous supply of the colon and rectum might influence anastomosis leak rates. Calcification in great blood vessels can be assessed with a preoperative computed tomography scan, which may predict anastomosis leak rates. This is supported by many experimental studies that showed increased rates of anastomosis leak after preoperative ischemia, but the extent of this impact is not well established. Preoperative assessment of blood supply to the colon and rectum might help in planning the surgical intervention to reduce anastomosis leak rates. Calcium scoring of major arteries might predict anastomosis leak and thus play a crucial role in intraoperative decision-making.


The peripherally inserted central catheter.
Peripherally inserted central catheters (PICCs) are commonly inserted by nurses. This article gives an overview of the care and management of the PICC in general adult nursing.


Revealing the catalytic pathway of a quinone-mediated oxygen reduction reaction in aprotic Li-O2 batteries.
Soluble redox species that facilitate the oxygen reduction reaction by mediating the LiO2 intermediate and consequently the formation of the Li2O2 have attracted considerable interest for Li-O2 batteries. Based on extensive radical studies, this work discloses a distinct solution reaction route when a quinone derivative was employed as a redox mediator.


Measurement of Optic Disc Cup Surface Depth Using Cirrus HD-OCT.
To introduce the measurement method of optic disc cup surface depth using spectral-domain optical coherence tomography (SD-OCT) and then evaluate the rates of cup surface depression at 3 different stages of glaucoma. We retrospectively identified 52 eyes with preperimetric glaucoma, 56 with mild-or-moderate glaucoma and 50 with severe glaucoma and followed them for at least 48 months. Eyes were imaged using SD-OCT (Cirrus HD-OCT) at 12-month intervals. The mean cup surface depth was calculated using the following formula: Cup volume/(disc area×average cup-to-disc ratio)-200 μm. The rates of mean cup surface depression (μm/y) were significantly greater in mild-or-moderate glaucoma (-7.96±1.03) than in preperimetric (-3.11±0.61) and severe glaucoma (-0.70±0.12; all P<0.001). The percentile rates of mean cup surface depression (%/y) were significantly greater than those of average of retinal nerve fiber layer (RNFL) thinning (%/y) in preperimetric glaucoma (-1.64±0.12 vs. -1.11±0.07; P<0.001) and mild-or-moderate glaucoma (-4.20±0.33 vs. -3.14±0.19; P<0.001); and conversely, in severe glaucoma, mean cup surface depth changed slower than did average RNFL thickness (-0.64±0.06 vs. -0.75±0.08%/y; P<0.001). In early-to-moderate glaucoma, the cup surface depth changed faster than did the RNFL thickness. These results signify the possibility that SD-OCT-based estimation of cup surface depth might be useful for monitoring of glaucoma development and progression.


[The significance of screening tests for aneuploidies in populations at low and high maternal-age-related risk].
The aim of this study was to evaluate the validity of the triple test and the screen test in maternal populations at low and high maternal-age-related risk for fetal aneuploidy. As a whole, 9,680 pregnant women at low risk and 627 at high risk underwent the triple test; 2,780 pregnant women at low risk and 408 at high risk underwent the screen or combined test; sensitivity, specificity, false positives and detection rate were compared between populations using Student's t-test. The triple test showed a detection rate of 75% in the low and 83.3% in the high risk population with a difference (P<0.003) for detection of trisomies 21 and 18 between the 2 populations; the screen test had a detection rates of 100% and 90% in the 2 populations, respectively, with a difference (P<0.005) between the 2 tests. Both tests are reliable for screening aneuploidies in the low risk population, the screen test having better performance; in the high risk population, the number of invasive procedures can be reduced by 78% with the triple test and by 84% with the screen test.


[Subjective Weight Perception in Normal-Weight Adults - Results of the German Health Interview and Examination Survey for Adults (DEGS1)].
This study investigates the prevalence and socio-demographic distribution of subjective weight perceptions in 2,552 subjects aged 18-79 years with normal weight (according to the WHO classification) who took part in the nationally representative DEGS1 study of the Robert Koch Institute, Berlin. In total, barely half of normal-weight adults-both men and women- considered themselves "a little/much too thick" or "a little/much too thin" (discordant weight perception). Normal-weight women assessed themselves predominantly as too thick (38,6%; 95% CI: 35,7-41,6). A quarter of normal-weight men assessed themselves as too thin, whereas another fifth of normal-weight men considered themselves too thick. The proportion of discordant weight perceptions declined with rising age. In multivariate assessment, socio-economic status was no significant predictor. Results are discussed in reference to potential implications for prevention programs.


Vascular adaptation of the internal thoracic artery graft early and late after bypass surgery.
Flow mismatch between the supplying artery and the myocardial perfusion region has been observed in patients with internal thoracic artery grafts. Thus coronary flow changes of arterial (internal thoracic artery grafts) and saphenous (saphenous vein grafts) bypass grafts were studied early and late after coronary artery bypass grafting. Thirty patients undergoing elective bypass surgery (internal thoracic artery and saphenous vein grafts) were studied intraoperatively and (17 patients) 3 to 10 months postoperatively. Coronary flow was measured intraoperatively with the transit-time Doppler scanning technique. Postoperatively, flow velocity and coronary flow reserve were determined with the Doppler flow wire technique. Quantitative angiographic analysis was used to determine vessel size for calculation of absolute flow. Intraoperatively, internal thoracic artery graft flow was significantly lower than saphenous vein graft flow (31 +/- 8 vs 58 +/- 29 mL/min, P < .01). Postoperatively, internal thoracic artery graft flow increased significantly to 42 +/- 24 mL/min at 3 months and to 56 +/- 30 mL/min (P < .02 vs intraoperative value) at 10 months, respectively. However, saphenous vein graft flow remained unchanged over time (58 +/- 29 to 50 +/- 27 mL/min at 3 months and 46 +/- 27 mL/min at 10 months). Coronary flow reserve was abnormally low intraoperatively in the internal thoracic artery (1.3 +/- 0.3) and saphenous vein (1.6 +/- 0.5) grafts but increased significantly to normal values in both types of graft at follow-up. Bypass flow of the internal thoracic artery graft is significantly reduced intraoperatively when compared with that of the saphenous vein graft. However, 3 and 10 months after the operation, flow of the internal thoracic artery graft increases significantly and is similar to saphenous vein graft flow. This finding can be explained by an early flow mismatch of the native internal thoracic artery in the presence of a large perfusion territory. During follow-up, there is vascular remodeling of the internal thoracic artery, probably because of endothelium-mediated mechanisms.


A report of four different unusual 6-PGD electrotypes in Caucasian and Negro populations.
Four different unusual 6-phosphogluconate dehydrogenase (6-PGD) electrophoretic patterns found among the Italian (Rome), Bamileke (Cameroon), and North Bateke and Babenga Pygmy (Congo) populations are described.


Rasch Analysis of the General Self-Efficacy Scale in Workers with Traumatic Limb Injuries.
Purpose The purpose of this study was to apply Rasch analysis to examine the unidimensionality and reliability of the General Self-Efficacy Scale (GSE) in workers with traumatic limb injuries. Furthermore, if the items of the GSE fitted the Rasch model's assumptions, we transformed the raw sum ordinal scores of the GSE into Rasch interval scores. Methods A total of 1076 participants completed the GSE at 1 month post injury. Rasch analysis was used to examine the unidimensionality and person reliability of the GSE. The unidimensionality of the GSE was verified by determining whether the items fit the Rasch model's assumptions: (1) item fit indices: infit and outfit mean square (MNSQ) ranged from 0.6 to 1.4; and (2) the eigenvalue of the first factor extracted from principal component analysis (PCA) for residuals was <2. Person reliability was calculated. Results The unidimensionality of the 10-item GSE was supported in terms of good item fit statistics (infit and outfit MNSQ ranging from 0.92 to 1.32) and acceptable eigenvalues (1.6) of the first factor of the PCA, with person reliability = 0.89. Consequently, the raw sum scores of the GSE were transformed into Rasch scores. Conclusions The results indicated that the items of GSE are unidimensional and have acceptable person reliability in workers with traumatic limb injuries. Additionally, the raw sum scores of the GSE can be transformed into Rasch interval scores for prospective users to quantify workers' levels of self-efficacy and to conduct further statistical analyses.


Purification and partial sequence analysis of human interleukin-2 derived from peripheral blood leukocytes.
Human peripheral blood leukocyte-derived interleukin-2 (IL-2) was resolved by DEAE-cellulose column chromatography into three peaks of activity, IL-2A, B, and C, with isoelectric points of 7.2, 6.6, and 7.9, respectively. IL-2 A, B, and C were further purified by reverse phase high performance liquid chromatography and resolved into two apparently homogeneous peaks each with identical molecular weight: A-1 and A-2 (Mr17000); B-1 and B-2 (Mr17500); and C-1 and C-2 (Mr14400). The amino acid compositions and partial NH2-terminal amino acid sequences of these molecular species were consistent with those predicted from IL-2 cDNA sequences derived from Jurkat and peripheral blood leukocytes.


Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function.
The HRAS gene plays a crucial role in regulating essential cellular processes for life, and this gene's misregulation is linked to the development of various types of cancers. Nonsynonymous single nucleotide polymorphisms (nsSNPs) within the coding region of HRAS can cause detrimental mutations that disrupt wild-type protein function. In the current investigation, we have employed in-silico methodologies to anticipate the consequences of infrequent genetic variations on the functional properties of the HRAS protein. We have discovered a total of 50 nsSNPs, of which 23 were located in the exon region of the HRAS gene and denoting that they were expected to cause harm or be deleterious. Out of these 23, 10 nsSNPs ([G60V], [G60D], [R123P], [D38H], [I46T], [G115R], [R123G], [P11OL], [A59L], and [G13R]) were identified as having the most delterious effect based on results of SIFT analysis and PolyPhen2 scores ranging from 0.53 to 69. The DDG values -3.21 kcal/mol to 0.87 kcal/mol represent the free energy change associated with protein stability upon mutation. Interestingly, we identified that the three mutations (Y4C, T58I, and Y12E) were found to improve the structural stability of the protein. We performed molecular dynamics (MD) simulations to investigate the structural and dynamic effects of HRAS mutations. Our results showed that the stable model of HRAS had a significantly lower energy value of -18756 kj/mol compared to the initial model of -108915 kj/mol. The RMSD value for the wild-type complex was 4.40 Å, and the binding energies for the G60V, G60D, and D38H mutants were -107.09 kcal/mol, -109.42 kcal/mol, and -107.18 kcal/mol, respectively as compared to wild-type HRAS protein had -105.85 kcal/mol. The result of our investigation presents convincing corroboration for the potential functional significance of nsSNPs in augmenting HRAS expression and adding to the activation of malignant oncogenic signalling pathways.