Assessments of skin and tongue microcirculation reveals major changes in porcine sepsis.
To examine the relation between central hemodynamics, clinical severity and microvascular findings in tongue and skin during sepsis. Skin and tongue microcirculation was examined using laser Doppler and video microscopy techniques before and 200 min after inducing sepsis in pigs (n=6) by inactivated Neisseria meningitides and in two control animals. All infected pigs developed clinical signs of sepsis. Pericapillary bleedings developed in the tongue in the two pigs with the most severe disease. Capillary density increased in the groin skin in infected pigs after 200 min as compared to baseline (P<0·02). In the same period, mean capillary flow velocity was reduced in groin skin and tongue in septic pigs (P<0·02). At 200 min a fraction of capillaries had developed 'no flow' or 'brisk flow', patterns hardly seen at baseline. Laser Doppler perfusion was reduced in ear and tongue after 200 min (P<0·02 for both). The described pathology was more pronounced in the pigs with the most severe sepsis. Capillary bleedings may be used as an early indication of severe sepsis. Examination of skin and tongue microcirculations may be used to characterize severity of sepsis and possibly to assess effect of treatment.


Recent increase in non-tuberculous mycobacterial infection in patients with connective tissue diseases in Japan.
Non-tuberculous mycobacterial (NTM) infection is currently a growing health concern due to the increasing incidence and the need for prolonged therapy. In patients with connective tissue diseases, use of immunosuppressants may lead to an increased risk of NTM infection. However, few studies have examined the recent incidence of NTM infection among connective tissue diseases patients. This study investigated recent trends in NTM infection among connective tissue diseases patients. We included adult patients from whose cultures NTM were isolated between January 2009 and October 2017 in our hospital. By reviewing their medical records, connective tissue diseases patients were identified. Types of connective tissue disease, NTM species, and treatment of NTM infection were extracted. NTM was isolated from 657 patients during the period. Among these, 24 patients had connective tissue diseases. The number and rate of NTM isolates from connective tissue diseases patients increased during the period, with 4 patients 2009 to 2012 (1.9%), and 20 patients from 2013 to 2017 (3.3%; P = 0.04). The proportion of Mycobacterium avium complex (MAC) to total NTM tended to be lower among connective tissue diseases patients (58.3%) than among non-connective tissue disease-patients (72.8%), but the difference was not significant (P = 0.20). Mycobacterium xenopi was significantly more frequent in connective tissue disease patients than in non-connective tissue diseases patients (P < 0.01). The recent increase in the incidence of NTM infections in connective tissue diseases patients was larger than that in the total population. NTM species other than MAC were isolated from connective tissue diseases patients.


Prognostic factors in malignant melanoma: a retrospective analysis of 182 patients.
The records of 182 patients with malignant melanoma, referred to the Regional Radiotherapy Centre, Newcastle upon Tyne, between January 1975 and December 1980, have been reviewed to determine the influence of site of disease, age and sex of the patient, Clark's levels and stage of disease on the prognosis. Site and age were found to have no influence on the survival rate. The difference in the survival rates of males and females was almost entirely accounted for by the difference in their disease at the time of presentation. Survival was found to be highly significantly affected by the Clark's levels (p less than 0.0001) and by the stage of disease (p less than 0.0001).


An ovine model of tachycardia-induced degenerative dilated cardiomyopathy and heart failure with prolonged onset.
The aim of this study was to develop a model of long-term progressive heart failure (HF). A cardiac output flowprobe was implanted on the pulmonary artery of 9 adult sheep weighing 40 to 50 kg. Rapid ventricular pacing for 21 days at 160 to 190 bpm (rate A) resulted in moderate HF. Animals were then paced at 205 to 215 bpm (rate B) for 42 days (severe HF) and for 28 days at rate B (advanced HF). Data were collected at baseline and moderate, severe, and advanced HF during submaximal exercise testing and by transthoracic echocardiography in sinus rhythm. There were marked increases in left ventricular (LV) area, mitral valve regurgitation, and LV end-diastolic pressure and decreases in LV wall thickness, LV ejection fraction, positive and negative dP/dt(max), and positive (dP/dt(max))/P throughout the pacing protocol. This ovine HF model incorporates the progressive nature of human HF and allows examination of both structural changes and hemodynamic parameters of HF during and after exercise challenge.


Cost-Effectiveness of Adult Spinal Deformity Surgery.
Review article. A review of the literature evaluating the cost-effectiveness of undergoing adult spinal deformity surgery and potential avenues for reducing costs. A review of the current literature and synthesis of data to provide an update on the cost effectiveness of undergoing adult spinal deformity surgery. Compared with nonoperative management, operative management for adult spinal deformity is associated with improved patient-reported outcomes and quality of life; however, it is associated with significant financial and resource use. Operative management for adult spinal deformity has been shown to be effective but is associated with significant cost and resource utilization. The optimal operative treatment is highly dependent on the patients' symptomatology and is surgeon dependent. Maximizing preoperative surgical health and minimizing postoperative complications are key measures in reducing the cost and resource utilization of adult spinal deformity surgery. Future studies are needed to evaluate how to optimize the cost-effectiveness.


Tryptophan metabolism and urinary quinoline bases in the greyhound.
Three quinoline bases may be found in greyhound urine. 2-aminomethylquinoline is excreted in fresh urine and two others, quinaldine and 2-hydroxymethylquinoline, are formed as the urine decays. Radiolabelling was employed to demonstrate that these bases are derived from the amino acid tryptophan.


Tamoxifen added to radiotherapy and surgery for the treatment of ductal carcinoma in situ of the breast: a meta-analysis of 2 randomized trials.
Surgical excision with adequate margins is the treatment of choice for ductal, in situ carcinoma of the breast (DCIS). The addition of radiotherapy (RT) halved local in situ and invasive recurrence. The purpose of our meta-analysis is to evaluate the reduction in recurrence (in situ or invasive) with the addition of tamoxifen (T), in particular in patients with DCIS treated with surgery+RT. The eligible studies (NSABP-B24 and UK ANZ DCIS trials) included prospective, randomized, controlled trials in which the addition of T had been compared with surgery+RT without T in women with DCIS of the breast. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated for both in situ and invasive recurrence (local and controlateral). Tamoxifen does not reduce breast cancer-specific or overall mortality when added to loco-regional therapy for DCIS of the breast (surgery plus or minus RT). Tamoxifen reduces overall breast cancer recurrence by 29% in all patients and by 33% in those treated with both surgery and RT. Only ipsilateral invasive (RR 0.61 [95% CI 0.41, 0.92]; p=0.02) and controlateral in situ relapses (RR 0.40 [95% CI 0.16, 0.96]; p=0.04) are significantly lowered when T is added to RT. Tamoxifen seems to exert a local synergistic effect with RT. Both young and older women (< and >50 years) achieve some benefit from the addition of T (RR 0.6 and 0.74, respectively). The addition of T to surgery and RT for DCIS of the breast reduces the risk of local invasive and controlateral in situ relapses, but not the survival. The benefit is independent of age. In conclusion, surgery associated with RT and T is the treatment of choice for patients with (estrogen-receptor positive) DCIS of the breast.


Suicide attempts in a national population of twins concordant for psychoses.
Psychotic disorders are associated with an increased risk of suicide attempts, the etiology of which remains unknown across diagnoses. Thus it is relevant to understand how genetic and environmental factors contribute to the liability of suicide attempts in psychosis. The current study aims to examine the role of genetic and environmental factors in suicide attempts across psychotic disorders in twins concordant for psychosis. The study population consisted of all twin pairs in the Israeli National Psychiatric Case Registry hospitalized with a last discharge diagnosis of a psychotic disorder. Twin pairs (N=116) were born between 1900 and 1993 and hospitalized from 1964 to 2001. Competing genetic models were examined to decompose the variance in suicide attempts into: the individual-specific environment (unique), shared-family environment, and genetic effects. Across schizophrenia, psychosis and non-affective psychosis comparison of genetic models showed a model combining shared-family and unique environmental effects were superior to competing genetic models. Modeling estimates for attempted suicide were: in non-affective psychosis 60% to the shared-family and 40% to the unique environment; in schizophrenia 60% to the shared-family and 40% to the unique environment; and in psychosis 66% to the shared-family and 34% to the unique environment. Across psychosis, schizophrenia and non-affective psychosis vulnerability toward suicide attempts consists predominantly of substantial individual and familial environmental elements.


Changes of pancreatic beta cell population during larval development of Rana pipiens.
The morphology and population size of immunohistochemically stained insulin-containing pancreatic beta cells are studied in Rana pipiens during larval development. These beta cells appear as single cells or form small clusters at early stages and gradually develop into large clusters arranged in cords surrounding the blood sinusoids in midlarval stages. The total quantity of these cells increases from stage II through midlarval stages, reaching maximum at stages XVIII and XIX. A significant decrease of total beta cell quantity is observed between stages XIX and XX. This decrease occurs slightly later than the onset of degeneration of exocrine tissue. Morphological indication of beta cell breakdown is also observed during this period. Although the population size of beta cells stays relatively constant from stages XXI to XXV, a further maturational change is observed in beta cell morphology between stages XXIV and XXV. During these stages, the polarization of stained immunoreactivity toward sinusoids is more obvious and there is a general decrease of staining intensity in the cytoplasm.


Deficiency of a transcriptional regulator, inhibitor of differentiation 3, induces glomerulonephritis in apolipoprotein E-deficient mice: a model linking hyperlipidemia and renal disease.
The clinical association between hyperlipidemia and renal disease is well established, yet hyperlipidemia as a cause for renal disease is rare. Apolipoprotein E-deficient (ApoE(-/-)) mice develop hyperlipidemia and are a model for atherosclerosis. Introducing deficiency of inhibitor of differentiation 3 (Id3) in ApoE(-/-) mice further exacerbates atherosclerosis. ID3 is a transcription regulator expressed in multiple cell types. Id3(-/-) mice develop antibodies to self-antigens and salivary gland autoimmunity. This study was undertaken to investigate a link between hyperlipidemia, autoimmunity, and renal disease. ApoE(-/-), Id3(-/-), and ApoE(-/-)Id3(-/-) double-knockout (DKO) mice were studied at different ages for renal pathological features and function. Serum samples were analyzed for the presence of autoantibodies. At 16 weeks, DKO mice developed mesangioproliferative glomerulonephritis (GN), leading to severe proteinuria. GN was associated with glomerular deposition of lipids and immune complexes and with macrophage infiltration. DKO mice had high levels of circulating autoantibodies. Although ApoE(-/-) mice had glomerular lipid deposits and Id3(-/-) mice had circulating autoantibodies, neither group of age-matched single-knockout mice developed GN. These data provide support for the hypothesis that induction of renal disease in hyperlipidemia is dictated by additional factors. Our study shows that some of these factors are regulated by ID3. Thus, ID3 is a novel risk factor linking cardiovascular and renal disease.


High rates of embryo wastage with use of assisted reproductive technology: a look at the trends between 1995 and 2001 in the United States.
To determine what percentage of embryos achieved through assisted reproductive technology (ART) do not result in a live birth and to examine the relationships among the number of embryos transferred, infants delivered, and embryos wasted. Retrospective correlational study of the U.S. summary data of ART results for the years of 1995-2001. Fertility clinics reporting data to the Society of Assisted Reproductive Technology (SART). None. Statistics for ART cycles using fresh, nondonor eggs and embryos were derived, and the percentage of embryos wasted each year was calculated. Trends over time were evaluated for percent embryos wasted, the average number of embryos transferred, and the delivery per transfer rate. Correlations between these variables were analyzed. The percentage of embryos transferred that did not produce a live birth was 90.8 in 1995 and decreased to 84.9 in 2001. This trend significantly correlated with a reduction in the number of embryos transferred (from 3.9 to 3.1) and with an improvement in delivery rate per transfer (25% to 33.4%). The vast majority of embryos produced in vitro and transferred fail to develop into an infant, supporting the concept that only a small fraction of embryos has the capacity to become a live birth. Clinicians should strive to reduce embryonic wastage without an adverse effect on delivery rates by perfecting methods of ovarian stimulation and embryo screening, and by transferring fewer embryos.


Equating context conditioning in Pavlovian incubation of US signal value.
The present study replicated the finding by Goddard (2013), that when a single food pellet unconditioned stimulus (US) signaled the delivery of three additional pellets, responding after the single US was significantly greater on a delayed, compared to an early, test. Importantly, the present study equated context conditioning by delivering the identical number of food pellets in both conditioning and testing and showed that responding was significantly reduced in control subjects that had received unpaired single food-triple food presentations. Implications for theories of conditioning are considered.


Rapid and accurate viral diagnosis.
In recent years, there has been increased recognition of the importance of viral infections. In addition, new antiviral agents have become available. These factors have led to a marked increase in utilization of viral diagnostic services. In this review, both conventional and rapid methods for viral diagnosis are presented, with emphasis on recent advances. The antiviral agents currently available and the major drugs under investigation are also briefly discussed. It is hoped that this review will serve as a useful adjunct for the management of patients with virus infections.


Spatial variation in the association between agricultural activities and bird communities in Canada.
Agriculture is one the main drivers of bird decline in both Europe and North America. While it is clear that agricultural practices and changes in the rural landscape directly and indirectly affect bird communities, we still do not know the extent to which these impacts might change across broad spatial and temporal scales. To address this question, we combined information on agricultural activities with occurrence and abundance of 358 bird species across five time periods spanning 20 years in Canada. As a proxy for agricultural impact, we used a combined index that included different agricultural metrics, such as cropland and tillage area and area treated with pesticides. We found that agriculture impact was negatively associated with bird diversity and evenness across all 20 years studied, but these associations seemed to vary by region. We found good support for an overall negative association between agriculture impact and bird diversity and evenness in the Eastern and Atlantic regions but weaker associations in the Prairies and Pacific. These findings suggest that agricultural activities result in bird communities that are less diverse and disproportionately benefit certain species. The spatial variation in the impact of agriculture on bird diversity and evenness we observed is likely a result of regional differences in the native vegetation, the type of crops and commodities produced, the historical context of agriculture, as well as the native bird community and the extent of their association with open habitat. Thus, our work provides support for the idea that the on-going agricultural impact on bird communities, while largely negative, is not uniform, and can vary across broad geographic regions.


A novel Bcl-x splice product, Bcl-xAK, triggers apoptosis in human melanoma cells without BH3 domain.
Pro- and antiapoptotic proteins of the large Bcl-2 family are critical regulators of apoptosis via the mitochondrial pathway. Whereas antiapoptotic proteins of the family share all four Bcl-2 homology domains (BH1-BH4), proapoptotic members may lack some of these domains, but all so far described proapoptotic Bcl-2 proteins enclose BH3. The bcl-x gene gives rise to several alternative splice products resulting in proteins with distinct functions as the antiapoptotic Bcl-xL and proapoptotic Bcl-xS. Here, we describe a novel Bcl-x splice product of 138 amino acids termed Bcl-xAK (Atypical Killer), which encloses the Bcl-2 homology domains BH2 and BH4 as well as the transmembrane domain, but lacks BH1 and BH3. Weak endogenous expression of Bcl-xAK was seen in melanoma and other tumor cells. Interestingly, its overexpression by applying a tetracycline-inducible expression system resulted in significant induction of apoptosis in melanoma cells, which occurred in synergism with drug-induced apoptosis. After exogenous overexpression, Bcl-xAK was localized both in mitochondrial and in cytosolic cell fractions. By these findings, a completely new class of Bcl-2-related proteins is introduced, which promotes apoptosis independently from the BH3 domain and implies additional, new mechanisms for apoptosis regulation in melanoma cells.


Urinary metabolomics of phenolic compounds reveals biomarkers of type-2 diabetes within the PREDIMED trial.
Phenolic compounds have been associated with protective effects against type-2 diabetes (T2D). We used a metabolomics approach to determine urinary phenolic metabolites associated with T2D and fasting plasma glucose. This case-control study within the PREDIMED trial included 200 participants at high cardiovascular risk, 102 of whom were diagnosed with T2D. A panel of urinary phenolic compounds were analysed using a novel method based on liquid chromatography coupled to mass spectrometry. Multivariate statistics and adjusted logistic regressions were applied to determine the most discriminant compounds and their association with T2D. The relationship between the discriminant phenolic compounds and plasma glucose was assessed using multivariable linear regressions. A total of 41 phenolic compounds were modeled in the orthogonal projection to latent structures discriminant analysis, and after applying adjusted logistic regressions two were selected as discriminant: dihydrocaffeic acid (OR = 0.22 (CI 95 %: 0.09; 0.52) per 1-SD, p-value = 0.021) and genistein diglucuronide (OR = 0.72 (CI 95%: 0.59; 0.88) per 1-SD, p-value = 0.021). Both metabolites were associated with a lower risk of suffering from T2D, but only dihydrocaffeic acid was inversely associated with plasma glucose (β = -17.12 (95 % CI: -29.92; -4.32) mg/dL per 1-SD, p-value = 0.009). A novel method using a metabolomics approach was developed to analyse a panel of urinary phenolic compounds for potential associations with T2D, and two metabolites, dihydrocaffeic acid and genistein diglucuronide, were found to be associated with a lower risk of this condition.


Twelve-year experience with the Carpentier-Edwards pericardial aortic valve at a single Japanese center.
Our aim was to evaluate the long-term results of implantation of the Carpentier-Edwards pericardial (CEP) valve in the aortic position. Between January 1996 and December 2007, 244 patients who underwent aortic valve replacement using the CEP valve were enrolled in this study. A 19-mm valve was used in 39 patients, a 21-mm valve in 94 patients, a 23-mm valve in 81 patients, and a 25-mm valve in 30 patients. The early and the late results were evaluated. Furthermore, echocardiographic examination was performed at follow-up. There were 5 early deaths, with an early mortality rate of 2.0%. Follow-up was performed in 95.4% of the survivors of the operation for a mean period of 4.1 years. Actuarial survival rates at 5, 10, and 12 years were 85.3 ± 2.8, 80.0 ± 3.7 and 70.0 ± 9.8%, respectively. Thromboembolism was observed in 6 patients, endocarditis in 2 patients, reoperation in 4 patients, and structural valve deterioration in 2 patients. Actuarial freedoms from thromboembolism, endocarditis, and reoperation at 10 years were 96.9 ± 0.14, 97.7 ± 0.16, and 97.0 ± 0.16%, respectively. Echocardiographic examination revealed that the pressure gradients across the valve prosthesis for valves of each size were acceptable. Left ventricular mass index decreased significantly in all valve sizes. The long-term results of implantation of the CEP bioprosthesis in the aortic position were satisfactory. The CEP bioprosthesis maintained its hemodynamic performance even as late as 10 years after implantation.


Early clinical outcomes and comparison between trans-PRK and PRK, regarding refractive outcome, wound healing, pain intensity and visual recovery time in a real-world setup.
To compare early clinical outcomes of single-step transepithelial photorefractive keratectomy (tPRK) and photorefractive keratectomy (PRK) regarding refractive outcome, visual acuity, wound healing, pain intensity and visual recovery time.d. In this prospective clinical observational study 200 eyes of 100 consecutive patients with mild to moderate myopia with or without mild astigmatism were included. One hundred eyes each were either treated with StreamLight™ tPRK or PRK with the WaveLight® EX500 excimer laser. Visual acuity (Decimal) was assessed preoperatively and at day 4, 7 and 6 weeks postoperatively. Wound healing (hours between surgery and complete epithelial closure) was monitored at the slit lamp. At day 4, patients subjectively rated the maximum pain intensity within the last 4 days using a numerical pain rating scale (0-15). Visual recovery was significantly faster in the tPRK group. At days 4 and 7, the mean monocular UCDVA was significantly better in the tPRK group than in the PRK group (p < 0.001). Four days after surgery 72 % of eyes in the tPRK group but no eye in the PRK had a UCDVA of 0.7 or better. At six weeks postoperatively, a UCDVA of 1.0 or better was achieved in both groups. Complete epithelial wound closure was achieved significantly faster in the tPRK group (p < 0.0001) and maximum pain level within the first 4 days after surgery was significantly lower in the tPRK group (p < 0.0001). No patient had lost a line of BCDVA and no complications or adverse effects were observed. According to our early clinical results, both treatments options appear to be safe and effective methods for the correction of low to moderate myopia with and without astigmatism. However, in our study, StreamLight™ tPRK offered faster visual recovery and epithelial healing and was associated with less pain compared to PRK. It can therefore be considered a good treatment option for patients who refuse or are not eligible for Femto-LASIK, but at the same time demand a faster and more comfortable recovery time than PRK can offer.


Evaluation of immunostimulatory attributes of Asparagus racemosus and Withania somnifera supplemented diets in fish, Channa punctatus (Bloch, 1793).
With the progression of aquaculture industry, there has been a spurt in dietary supplementation with economically viable medicinal herbs having enough immunostimulatory potential. This also aids in avoidance of environmentally undesirable therapeutics that are almost inevitable to safeguard fish against an array of diseases in aquaculture practices. The study aims to determine the optimal dose of herbs that can stimulate substantial immune response in fish for reclamation of aquaculture. Immunostimulatory potential of the two medicinal herbs- Asparagus racemosus (Shatavari), Withania somnifera (Ashwagandha), individually, and in combination, with a basal diet was screened up to 60 days in Channa punctatus. 300 laboratory acclimatized healthy fish (14 ± 1 g; 11 ± 1 cm) were divided into ten groups- C, S1, S2, S3, A1, A2, A3, AS1, AS2, and AS3, based on the composition of dietary supplementation, in triplicates, with 10 specimens per group. The hematological index, total protein and lysozyme enzyme activity were performed after 30 and 60 days, while qRT-PCR analysis of lysozyme expression was done after 60 days of the feeding trial. The significant (P < 0.05) increments in hematological indices- (TEC, TLC, DLC, Hb, Hct, MCV, MCH and MCHC), total protein content and serum lysozyme activity, after 30 and 60 days; whereas upregulation of lysozyme transcript levels, both in liver and muscle tissues after 60 days of the feeding trial were recorded in groups- AS1, AS2, and AS3. The maximal increment in lysozyme expression was recorded in AS3, both in liver and muscle tissues, with 3.75 ± 0.13 and 3.21 ± 0.18-folds, respectively. However, increments were non-significant (P > 0.05) for MCV in AS2 and AS3 after 30 days; and for MCHC in AS1 for both the durations; whereas in AS2 and AS3, after 60 days of the feeding trial. A positive correlation (P < 0.05) among lysozyme expression, MCH, lymphocytes, neutrophils, total protein content, and serum lysozyme activity in AS3, after 60 days, conclusively, evinces that a 3% dietary supplementation with both A. racemosus and W. somnifera enhances immunity and health profile of the fish, C. punctatus. The study, thus finds ample scope in augmentation of aquaculture production and also paves the way for more researches for biological screenings of potential immunostimulatory medicinal herbs that can be appropriately incorporated in the fish diet.


Thoracostomy in children with severe trauma: An overview of the paediatric experience in Victoria, Australia.
Thoracic trauma is a leading cause of paediatric trauma deaths. Traumatic cardiac arrest, tension pneumothorax and massive haemothorax are life-threatening conditions requiring emergency and definitive pleural decompression. In adults, thoracostomy is increasingly preferred over needle thoracocentesis for emergency pleural decompression. The present study reports on the early experience of thoracostomy in children, to inform debate regarding the best approach for emergency pleural compression in paediatric trauma. Retrospective review of Ambulance Victoria and The Royal Children's Hospital Melbourne, Trauma Registry between August 2016 and February 2019 to identify children undergoing thoracostomy for trauma, either pre-hospital or in the ED. Fourteen children aged 1.2-15 years underwent 23 thoracostomy procedures over the 31 month period. The majority of patients sustained transport-related injuries, and underwent thoracostomies for the primary indications of hypoxia and hypotension. Two children were in traumatic cardiac arrest. Ten children underwent needle thoracocentesis prior to thoracostomy, but all required thoracostomy to achieve the necessary definitive decompression. All patients were severely injured with multiple-associated serious injuries and median Injury Severity Score 35.5 (17-75), three of whom died from their injuries. Thoracostomy in our cohort had a low complication rate. In severely injured children, thoracostomy is an effective and reliable method to achieve emergency pleural decompression, including in the young child. The technical challenges presented by children are real, but can be addressed by training to support a low complication rate. We recommend thoracostomy over needle thoracocentesis as the first-line intervention in children with traumatic cardiac arrest, tension pneumothorax and massive haemothorax. [Correction added on 23 September 2019 after first online publication: in the second sentence of the conclusion, the words "under review process" were mistakenly added and have been removed.].


A proteomic atlas of kidney amyloidosis provides insights into disease pathogenesis.
The mechanisms of tissue damage in kidney amyloidosis are not well described. To investigate this further, we used laser microdissection-mass spectrometry to identify proteins deposited in amyloid plaques (expanded proteome) and proteins over expressed in plaques compared to controls (plaque-specific proteome). This study encompassed 2650 cases of amyloidosis due to light chain (AL), heavy chain (AH), leukocyte chemotactic factor-2-type (ALECT2), secondary (AA), fibrinogen (AFib), apo AIV (AApoAIV), apo CII (AApoCII) and 14 normal/disease controls. We found that AFib, AA, and AApoCII have the most distinct proteomes predominantly driven by increased complement pathway proteins. Clustering of cases based on the expanded proteome identified two ALECT2 and seven AL subtypes. The main differences within the AL and ALECT2 subtypes were driven by complement proteins and, for AL only, 14-3-3 family proteins (a family of structurally similar phospho-binding proteins that regulate major cellular functions) widely implicated in kidney tissue dysfunction. The kidney AL plaque-specific proteome consisted of 24 proteins, including those implicated in kidney damage (α1 antitrypsin and heat shock protein β1). Hierarchical clustering of AL cases based on their plaque-specific proteome identified four clusters, of which one was associated with improved kidney survival and was characterized by higher overall proteomic content and 14-3-3 proteins but lower levels of light chains and most signature proteins. Thus, our results suggest that there is significant heterogeneity across and within amyloid types, driven predominantly by complement proteins, and that the plaque protein burden does not correlate with amyloid toxicity.


Characterization of free radical-induced damage to DNA by the combined use of enzymatic hydrolysis and gas chromatography-mass spectrometry.
The use of gas chromatography-mass spectrometry (GC-MS) for characterization of free radical-induced base damage to DNA is presented. Damage introduced to DNA by reactive oxygen species such as hydroxyl radicals appears to play an important role in mutagenesis, carcinogenesis and aging. Elucidation of the chemical nature of such DNA lesions is necessary for the assessment of their biological consequences and enzymatic repair. DNA exposed to radiation-generated hydroxyl radicals in aqueous solution was hydrolyzed to 2'-deoxyribonucleosides with a mixture of DNase I, venom and spleen exonucleases and alkaline phosphatase. The hydrolysate was subsequently trimethylsilylated and analyzed by GC-MS. A large number of DNA lesions were separated and identified. Mass spectra obtained were interpreted on the basis of the typical fragmentation pathways of trimethylsilylated nucleosides. The use of GC-MS with selected-ion monitoring facilitated the detection of these lesions at the very low quantities and radiation doses (below 10 Gray) that might be relevant to those in biological systems.


The use of Kumpfer's resilience framework in understanding the breastfeeding experience of employed mothers after returning to work: a qualitative study in China.
The increasing numbers of women in the workforce is an inevitable trend in China. More and more employed women stop breastfeeding because of working stressors. Many mothers, however, overcome the challenges and insist on breastfeeding after returning to work. Their individual experience of breastfeeding may provide a new insight to promote and support breastfeeding on employed mothers. This study sought to understand mothers' experience with insisting on breastfeeding after returning to work based on Kumpfer's Resilience Framework in Chinese context. This qualitative study was designed with semi-structured interviews. Purposive sampling and snowball sampling were employed to recruit 13 full-time working mothers with a stable job in the public sector who continued to breastfeed for 1 month or longer after returning to work in Haikou, Hainan Province, China. Interviews were conducted from January to March 2020 to capture participants' experiences of breastfeed after returning to work. Grounded theory and Kumpfer's Resilience Framework were used to analyze data via a systematic and iterative process. Employed mothers built resilience while continuing to breastfeed after returning to work. The core concept was "dynamic interaction". Other categories were the background and explanation of this phenomenon. For working mothers who continued to breastfeed, resilience involved "dynamic interaction", which started from "experiencing stressors" and "obtaining support", two environmental factors interacted with the individual to "build resilience qualities", which interact with environment led to "behavioral resilience". And then the ongoing dynamic interaction between behavioral resilience and environment ultimately led to three different "weaning processes", including natural weaning, active weaning, and forced weaning. This study identified the framework of resilience in mothers who were in the adversity of breastfeeding after returning to work based on Kumpfer's Resilience Framework. It provided a new insight into the resilience of employed mothers around the world to continue breastfeeding and showed the different culture of breastfeeding on employed mothers.


'My midwife made childbirth a positive and enjoyable experience'.
I was expecting my first baby. I was nervous and in slow labour. When I called the maternity unit at Queen Elizabeth Hospital in Gateshead for reassurance over the phone, midwife Anna Marley was on shift.


Effect of age on sensory nerve conduction velocity in the horse.
This study aimed to establish a clinically reproducible method of evaluation of sensory nerve conduction in the horse and to provide reference values in a group of normal horses. Age-related changes in the sensory nerve conduction velocity were of particular interest. Sensory nerve conduction was performed in the lateral palmar nerve. The results revealed an increase in velocity over the first year of life and a subsequent decrease in velocity in older horses. The effect of age must be considered if results from horses in which peripheral nerve disease is suspected are to be interpreted correctly. The results reflect similar findings in man and other domestic species.


Effect of varying pacing waveform shapes on propagation and hemodynamics in the rabbit heart.
The propagation characteristics of myocardium stimulated with anodal, cathodal, and equiphasic biphasic pacing pulses were examined in Langendorff-perfused rabbit hearts. Conduction velocity measurements were made using an array of bipolar extracellular electrodes, transmembrane potentials recorded using floating intracellular microelectrodes, and hemodynamics measured by fluid-filled catheter transducer systems. Anodal (A) stimulation pulses improved the electrical conduction at all the stimulus amplitudes tested in both longitudinal (e.g., 5 V 2-msec pulse: [A] 54.9 +/- 0.7 cm/sec; cathodal [C] 49.7 +/- 1.5 cm/sec) and transverse (e.g., 5 V 2 msec pulse: [A] 31.3 +/- 1.7 cm/sec; [C] 23.3 +/- 2.9 cm/sec) directions. Microelectrode recordings verified that increased conduction velocities of the anodal pulses were associated with faster upstrokes of the action potentials. The increased threshold associated with anodal pulses may be overcome by using a biphasic (B) waveform, in effect adding a second phase (e.g., 2-msec pulse: [A] 2.03 +/- 1.3 V; [C] 3.85 +/- 1.5 V; [B] 2.15 +/- 0.9 V). The conduction speeds achieved by the biphasic pulses were found to be comparable to the equivalent anodal pulses (e.g., 5 V 2-msec pulse: [B] 55.2 +/- 1.7 cm/sec longitudinal and 32.4 +/- 2.1 cm/sec transverse). It is postulated that the enhanced conduction by anodal and biphasic pulses may be due to preconditioning of the myocardium before stimulation, resulting in more vigorous action potential upstrokes. In preliminary experiments, it was observed that improved conduction elicited by these pulses also resulted in enhanced contractility as measured by shortened electromechanical delays and faster rate of rise of pressure development (dP/dtmax: [A] 25.4 +/- 0.4 mm Hg/sec; [C] 19.4 +/- 0.8 mm Hg/sec; [B] 25.7 +/- 1.2 mm Hg/sec, respectively). Use of novel hybrid pulses involving an anodal component may offer a way for implanted pacemakers to enhance the electro-mechanical response of the heart.


Efficacy and Safety of Dual Antiplatelet Therapy in Patients Undergoing Coronary Stent Implantation: A Systematic Review and Network Meta-Analysis.
This network meta-analysis aimed to evaluate the efficacy and safety of different dual antiplatelet therapies (DAPTs) after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Randomized controlled trials (RCTs) comparing longer-term (>12 months) DAPT (L-DAPT), 12-month DAPT (DAPT 12Mo), 6-month DAPT (DAPT 6Mo), 3-month DAPT followed by aspirin monotherapy (DAPT 3Mo + ASA), 3-month DAPT followed by a P2Y12 receptor inhibitor monotherapy (DAPT 3Mo + P2Y12), or 1-month DAPT with a P2Y12 receptor inhibitor monotherapy (DAPT 1Mo + P2Y12) were searched. Primary endpoints were all-cause mortality, cardiac death, myocardial infarction (MI), major bleeding, any bleeding, definite or probable stent thrombosis (ST), and net adverse clinical events (NACE). This Bayesian network meta-analysis was performed with the random-effects model. Twenty-four RCTs (n = 81339) were included. In comparison with L-DAPT, DAPT 6Mo (OR: 0.50, 95% CI: 0.29-0.83), DAPT 3Mo + P2Y12 (OR: 0.38, 95% CI: 0.18-0.82), DAPT 3Mo + ASA (OR: 0.44, 95% CI: 0.17-0.98), and DAPT 1Mo + P2Y12 (OR: 0.45, 95% CI: 0.14-0.93) were associated with a lower risk of major bleeding. DAPT 3Mo + P2Y12 (OR: 0.58, 95% CI: 0.38-0.88) reduced the risk of any bleeding when compared with DAPT 12Mo. L-DAPT decreased the risk of MI and definite or probable stent ST when compared with DAPT 6Mo. DAPT 3Mo + P2Y12 decreased the risk of NACE in comparison with DAPT 6Mo and DAPT 12Mo. No significant difference in all-cause mortality and cardiac death was observed. In patients with acute coronary syndrome, DAPT 6Mo was comparable to DAPT 12Mo. Short-term (1-3 months) DAPT is noninferior to DAPT 6Mo after DESs implantation, while L-DAPT reduces MI and definite or probable ST rates. DAPT 3Mo + P2Y12 might be a reasonable trade-off in patients with high risk of bleeding accompanied by ischemia.


[Gastroesophageal reflux and the degree of esophagitis in patients with coronary heart disease: impact on myocardial repolarization parameters and cardiac rhythm variability].
The specific features of myocardial repolarizing processes and heart rate variability (HRV) were studied in 67 patients with coronary heart disease (CHD) concurrent with gastroesophageal reflux disease (GERD) (a study group), in 72 patients with CHD and in 46 patients with GERD (comparison groups). Patients with concomitant diseases showed a significant asynchronism of repolarizing processes and decreased HRV. A relationship was established between the presence and magnitude of inflammatory lower esophageal third changes, and the severity of myocardial repolarizing processes, and decreased HRV in patients with CHD + GERD.


Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate.
A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor-binding domain (RBD) and the S1 subunit (S1) of the spike protein of SARS-CoV-2 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate. In addition, hypoxia inhibits the binding of the spike to NCI-H460 human lung epithelial cells by decreasing the cell surface levels of heparan sulfate (HS), a known attachment receptor of SARS-CoV-2. This interaction is also reduced by lactoferrin, a glycoprotein that blocks HS moieties on the cell surface. The expression of syndecan-1, an HS-containing proteoglycan expressed in lung, is inhibited by hypoxia on a HIF-1α-dependent manner. Hypoxia or deletion of syndecan-1 results in reduced binding of the RBD to host cells. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signalling pathway might offer therapeutic opportunities for the treatment of COVID-19.


Neuromuscular compensation strategies adopted at the shoulder following bilateral subpectoral implant breast reconstruction.
Immediate two-stage subpectoral implant breast reconstruction after mastectomy requires the surgical disinsertion of the sternocostal fiber region of the pectoralis major (PM). The disinsertion of the PM would need increased contributions from intact shoulder musculature to generate shoulder torques. This study aimed to identify neuromuscular compensation strategies adopted by subpectoral implant breast reconstruction patients using novel muscle synergy analyses. Fourteen patients treated bilaterally with subpectoral implant breast reconstruction (>2.5 years post-reconstruction) were compared to ten healthy controls. Surface electromyography was obtained from sixteen shoulder muscles as participants generated eight three-dimensional (3D) shoulder torques in five two-dimensional arm postures bilaterally. Non-negative matrix factorization revealed the muscle synergies utilized by each experimental group on the dominant and non-dominant limbs, and the normalized similarity index assessed group differences in overall synergy structure. Bilateral subpectoral implant patients exhibited similar shoulder strength to healthy controls on the dominant and non-dominant arms. Our results suggest that 3D shoulder torque is driven by three shoulder muscle synergies in both healthy participants and subpectoral implant patients. Two out of three synergies were more similar than is expected by chance between the groups on the non-dominant arm, whereas only one synergy is more similar than is expected by chance on the dominant arm. While bilateral shoulder strength is maintained following bilateral subpectoral implant breast reconstruction, a closer analysis of the muscle synergy patterns underlying 3D shoulder torque generation reveals that subpectoral implant patients adopt compensatory neuromuscular strategies only with the dominant arm.


What-Where-When Memory in the Rodent Odor Span Task.
While the Odor Span Task (OST) was developed to assess working memory in rodents, it appears that odor ("What") and time since an odor was last reinforced ("When") jointly control responding in the OST. The OST uses an incrementing non-match to sample procedure such that the number of stimuli to remember increases during the session; the rodent is trained to remember stimuli within a session but not between sessions. We used a variation of the OST to add a "Where" dimension to the task to examine whether rodents could learn to respond to scents based on contextual cues as well. In Experiment 1, 6 rats well-trained on the OST procedure were exposed to four target scents in a holding cage before the OST session began [What-Where-When (WWW) condition]. When these target scents appeared in the OST, rats treated them as novel scents despite their being previously encountered that day; WWW responding was comparable to baseline (BL) responding. Controls were implemented to account for relative familiarity: frequency of target presentation and time since the target odor was presented. On both types of control probes, rats typically responded to target scents less than during WWW or BL conditions, took longer to make a response, and visited more comparison stimuli. In Experiment 2, the study was replicated adding reinforcement delivery for responding to pre-session presentation of target stimuli. Subjects were the same 6 rats plus 2 additional rats also well-trained on the OST. Results were similar to those from Experiment 1. These data indicate that the variables controlling performance on the OST task include What stimulus is presented, Where (i.e., in which location) it was presented, and When it was presented. Thus, the OST-probe methodology may provide a useful vehicle for the study of episodic-like memory processes in non-humans.


Performance evaluation of duplex constructed wetlands for the treatment of diesel contaminated wastewater.
A duplex constructed wetland (duplex-CW) is a hybrid system that combines a vertical flow (VF) CW as a first stage with a horizontal flow filter (HFF) as a second stage for a more efficient wastewater treatment as compared to traditional constructed wetlands. This study evaluated the potential of the hybrid CW system to treat influent wastewater containing diesel range organic compounds varying from C7 - C40 using a series of 12-week practical and numerical experiments under controlled conditions in a greenhouse (pH was kept at 7.0 ± 0.2, temperature between 20 and 23° C and light intensity between 85 and 100-μmol photons m-2 sec-1 for 16 h d-1). The VF CWs were planted with Phragmites australis and were spiked with different concentrations of NH4+-N (10, 30 and 60 mg/L) and PO43--P (3, 6 and 12 mg/L) to analyse their effects on the degradation of the supplied petroleum hydrocarbons. The removal rate of the diesel range organics considering the different NH4+-N and PO43--P concentrations were simulated using Monod degradation kinetics. The simulated results compared well with the observed database. The results showed that the model can effectively be used to predict biochemical transformation and degradation of diesel range organic compounds along with nutrient amendment in duplex constructed wetlands.


Prognostic factors for the development of lower respiratory tract infection after influenza virus infection in allogeneic hematopoietic stem cell transplantation recipients: A Kanto Study Group for Cell Therapy multicenter analysis.
Influenza virus infection (IVI) occasionally causes lower respiratory tract infection (LRTI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the progression to LRTI entails a high mortality, the role of early antiviral therapy for its prevention has not been fully elucidated. This was a multicenter retrospective study using an additional questionnaire. Allo-HSCT recipients who developed IVI between 2012 and 2020 were included. A total of 278 cases of IVI after allo-HSCT were identified from 15 institutions. The median patient age was 49 years, and the median time from allo-HSCT to IVI was 918 days. Neuraminidase inhibitors were administered within 48 hours of symptom onset (early neuraminidase inhibitor [NAI]) in 199 (76.9%) patients. Subsequently, 36 (12.3%) patients developed LRTI. On the multivariate analysis, age ≥50 years (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.02-4.58) and moderate to severe chronic graft-versus-host disease (HR, 2.28; 95% CI, 1.14-4.58) were significantly associated with progression to LRTI, whereas early NAI suppressed the progression (HR, 0.17; 95% CI, 0.06-0.46). The IVI-related mortality rate was 2.2%. To reduce the risk of LRTI development after IVI, early NAI therapy should be considered in allo-HSCT recipients, especially with older patients and those with chronic graft-versus-host disease.


Medication Use and Fall-Related Hospital Admissions from Long-Term Care Facilities: A Hospital-Based Case-Control Study.
Falls are a leading cause of preventable hospitalizations from long-term care facilities (LTCFs). Polypharmacy and falls-risk medications are potentially modifiable risk factors for falling. This study investigated whether polypharmacy and falls-risk medications are associated with fall-related hospital admissions from LTCFs compared with hospital admissions for other causes. This was a hospital-based, case-control study of patients aged ≥65 years hospitalized from LTCFs. Cases were patients with falls and fall-related injuries, and controls were patients admitted for infections. Conditional logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between polypharmacy (defined as the use of nine or more regular pre-admission medications) and falls-risk medications (categorized as psychotropic medications and those that can cause orthostatic hypotension) with fall-related hospital admissions. There was no association between polypharmacy and fall-related hospital admissions (adjusted OR 0.97, 95% CI 0.63-1.48); however, the adjusted odds of fall-related hospital admissions increased by 16% (95% CI 3-30%) for each additional falls-risk medication. Medications that can cause orthostatic hypotension (adjusted OR 1.25, 95% CI 1.06-1.46), but not psychotropic falls-risk medications (adjusted OR 1.02, 95% CI 0.88-1.18) were associated with fall-related hospital admissions. The association between medications that can cause orthostatic hypotension and fall-related hospital admissions was strongest among residents with polypharmacy (adjusted OR 1.44, 95% CI 1.08-1.92). Polypharmacy was not an independent risk factor for fall-related hospital admissions; however, medications that can cause orthostatic hypotension were associated with fall-related hospital admissions, particularly among residents with polypharmacy. Falls-risk should be considered when prescribing medications that can cause orthostatic hypotension.


Rapid Onset of Relapsing Longitudinally Extensive Transverse Myelitis After Lumbar Spinal Surgery.
A 58-year-old woman experienced relapsing acute longitudinally extensive transverse myelitis that developed rapidly in 3 days after lumbar surgery. The patient had a history of systemic lupus erythematosus with acute transverse myelitis and had undergone plasmapheresis 16 years ago. New neurologic deficits including paraplegia of the lower limbs, sensory alterations, and bowel incontinence presented 3 days postoperatively. Magnetic resonance imaging revealed a long-segment hyperintense signal over the thoracic spine on T2-weighted imaging. Intravenous pulse therapy with high-dose corticosteroid was first used for 5 days but was ineffective. Plasmapheresis after pulse therapy resulted in improved neurologic deficit. The patient then underwent 6 months of rehabilitation therapy but was partially wheelchair bound. She no longer had bladder and bowel incontinence.


Functional Near-Infrared Spectroscopy Evidence of Prefrontal Regulation of Cognitive Flexibility in Adults With ADHD.
Executive function (EF) deficit is considered to be a core cognitive deficit in ADHD. The current study combined functional near-infrared spectroscopy (fNIRS) and numerical switching tasks to investigate the cognitive flexibility of adult ADHD as an important part of EF. The Wender Utah Rating Scale and the adult ADHD self-rating scale were respectively used to assess ADHD symptoms in childhood and adulthood. A 22 adults with ADHD and 24 healthy controls (HCs) participated in the large/small and odd/even switching tasks. Behavioral results were indicative of the ADHD switch costs being lower than the HCs. The fNIRS results also showed that ADHD's frontal eye field was over-activated both in magnitude and switched judgment tasks. The dorsolateral prefrontal cortex was also over-activated in magnitude judgment tasks. These results revealed that adults with ADHD's cognitive flexibility performed better than the HCs, which result is different from mainstream ideas that EF is a core deficit in ADHD.


Fatty acids. Part 48. 13C nuclear magnetic resonance studies of acetylenic fatty acids.
The 13C NMR spectra of thirty-seven alkynoic acids (C8-C18) and ten alkadiynoic acids (C18 and C20) are reported and interpreted. The influence of COOH, COOCH3, CH3, and C identical to C groups on the chemical shifts of nearby carbon atoms is assessed. These influences are largely additive so that available spectra are readily interpreted and the spectra of new compounds of this type can be predicted. These preliminary results indicate that 13C NMR spectroscopy should be of considerable value in the structural identification of acetylenic compounds.


Pandemic H1N1 influenza-associated hospitalizations in children in Madrid, Spain.
To describe the epidemiological and clinical characteristics of children hospitalized with 2009 pandemic influenza (pH1N1) in Madrid, Spain. We included patients less than 14 years of age admitted to one of 18 hospitals in Madrid, Spain, between May 1 and November 30, 2009 and diagnosed with pH1N1 by polymerase chain reaction. A retrospective chart review was conducted and data were compared by age, presence of high-risk medical conditions, and pediatric intensive care unit (PICU) admission. A total of 517 pH1N1 cases were included for final analysis. One hundred and forty-two patients (27·5%) had predisposing underlying illnesses, with immunosuppression (36 children, 7%) and moderate persistent asthma (34, 6·6%) being the most common ones. Patients with underlying medical conditions had longer hospital stays [median 5, interquartile range (IQR) 3-8 days, versus median 4, IQR 3-6, P < 0·001] and required intensive care (20·4% versus 5·9%, P < 0·001) and mechanical ventilation more frequently than previously healthy children. Globally, intensive care was required for 51 patients (10%) and invasive mechanical ventilation for 12 (2%). Pediatric intensive care unit admission was significantly associated with abnormal initial chest X-ray [Odds Ratio (OR) 3·5, 95% confidence interval (CI) 1·5-8·5], underlying neurological condition (OR 3·1, CI 1·2-7·5) and immunosuppression (OR 2·9, 1·2-6·8). Five patients (0·9%) died; two with severe neurological disease, two with leukemia, and one with a malignant solid tumor. Children with underlying medical conditions experienced more severe pH1N1 disease. Risk factors for admission to the PICU included underlying neurological conditions, immunosuppression and abnormal initial chest X-ray.


Body Mass Index and Lymphedema Morbidity: Comparison of Obese versus Normal-Weight Patients.
Obesity is a risk factor for the development of secondary lymphedema after axillary lymphadenectomy and radiation therapy. The purpose of this study was to determine whether obesity influences the morbidity of lymphedema in patients who have the condition. Two cohorts of patients were compared: group 1, normal weight (body mass index ≤25 kg/m); and group 2, obese (body mass index ≥30 kg/m). Inclusion criteria were patients aged 21 years or older with lymphedema confirmed by lymphoscintigraphy. Covariates included age, sex, lymphedema type (primary or secondary), location, comorbidities, lymph node dissection, radiation therapy, lymphoscintigram result, and disease duration. Outcome variables were infection, hospitalization, and degree of limb overgrowth. The cohorts were compared using the Mann-Whitney U test, Fisher's exact test, and multivariable logistic regression. Sixty-seven patients were included: group 1, n = 33; and group 2, n = 34. Disease duration did not differ between groups (p = 0.72). Group 2 was more likely to have an infection (59 percent), hospitalization (47 percent), and moderate or severe overgrowth (79 percent), compared to group 1 (18, 6, and 40 percent, respectively; p < 0.001). Multivariable logistic regression showed that obesity was an independent risk factor for infection (OR, 7.9; 95 percent CI, 2.5 to 26.3; p < 0.001), hospitalization (OR, 30.0; 95 percent CI, 3.6 to 150.8; p < 0.001), and moderate to severe limb overgrowth (OR, 6.7; 95 percent CI, 2.1 to 23.0; p = 0.003). Obesity negatively affects patients with established lymphedema. Obese individuals are more likely to have infections, hospitalizations, and larger extremities compared to subjects with a normal body mass index. Patients with lymphedema should be counseled about the negative effects of obesity on their condition. Risk, II.


Standard polypropylene mesh vs lightweight mesh for Lichtenstein repair of primary inguinal hernia: a randomized controlled trial.
The aim of the present clinical study was to compare early and late outcomes after inguinal hernia repair with the heavyweight mesh (HW) and lightweight mesh (LW) during a 3 year follow-up period. 226 patients were randomized into LW and HW mesh groups, both of which underwent unilateral primary inguinal hernia repair via the Lichtenstein technique. Wound complications (infection, hematoma, seroma), hernia recurrence, pain and feeling of foreign body in inguinal area were determined in patients. Pain was measured by visual analogue scale. No statistical difference has been found between LW and HW groups by wound complication (P = 0.80). One case of hernia recurrence has been mentioned in both groups one year after hernioplasty. But there was no detectable difference between the two groups. No significant difference has been found between LW and HW groups by frequency of chronic pain 7 days, 1 and 3 months, 1, 2, and 3 years after surgery. As for the feeling of foreign body in groin it is similar in both groups after 1 and 3 months. Level of feeling of foreign body was significantly lower in LW group 1, 2, and 3 years after surgery, than in HW group (P = 0.03, P = 0.02, P = 0.02, respectively). Our research shows no significant difference in wound complications, hernia recurrence and chronic pain after Lichtenstein hernioplasty, by using of LW and HW meshes. The usage of the LW mesh was associated with less feeling of foreign body than that of the HW mesh, what can be considered as prevalence of LW mesh hernioplasty.


Interferon Gamma-Mediated Oxidative Stress Induces Apoptosis, Neuroinflammation, Zinc Ion Influx, and TRPM2 Channel Activation in Neuronal Cell Line: Modulator Role of Curcumin.
Host defenses in the brain are modulated by the activation of several factors such as oxygen free radical species (ROS), Ca2+ influx, and TRPM2 activation, and they are well-known adverse factors in neurotoxicity and neurodegenerative diseases. Importantly, recent data indicated a protective action of curcumin (CRC) via inhibition of TRPM2 on the inflammation factors, ROS, and apoptosis in hypoxia-induced SH-SY5Y neuronal cells. However, the relationship between interferon gamma (IFNg) exposure and TRPM2 activation in the SH-SY5Y cells are not fully identified. The SH-SY5Y cells as a neuronal cell line model were used in several neuroinflammation studies. Hence, we used the SH-SY5Y cells in the current study, and they were divided into four main groups as control, CRC, IFNg, and IFNg+CRC. The data presented here indicate that IFNg induced excessive Ca2+ influx via activation of TRPM2. The IFNg treatment further increased cell death, cell debris amount, apoptosis, and cytokine generations (IL-1β, IL-6, and TNF-α) which were due to increased cytosolic and mitochondrial ROS generations as well as increased activations of caspase-3 and caspase-9. The expression levels of TRPM2, PARP-1, Bax, caspase-3, and caspase-9 were increased in the cells by the IFNg treatment. However, CRC treatment reduced the increase of expression levels, cytokine generations, caspase activations, ROS release, Ca2+ influx, cell death, and apoptosis levels via inhibition of TRPM2 in the SH-SY5Y cells that were treated with IFNg. Moreover, the treatment of TRPM2 blockers (ACA and 2-APB) potentiated the modulator effects of CRC. In conclusion, these results suggest that neuroinflammation via IFNg lead to the TRPM2 activation in the SH-SY5Y cells, whereas CRC prevents IFNg-mediated TRPM2 activation, cell death, and cytokine generations.


Risk-based concentrations: prioritizing environmental problems using limited data.
A difficult task faced by regulatory agencies is that of choosing, on the basis of limited data, which environmental problems to address. This paper incorporates USEPA risk assessment methods into a quantitative approach for prioritizing locations, contaminants and media according to potential health risk. USEPA has developed either a reference dose (a chronic dose without adverse effect) or slope factor (upper bound lifetime cancer risk per mg.kg-1.d-1) for many substances. This work combines these 'toxicological constants' with predetermined risk levels (either a 10(-6) cancer risk or a chronic intake equal to the reference dose) and protective human exposure assumptions (e.g. 70-kg body mass, 30-year exposure, 2-1.d-1 drinking water ingestion, etc.) to produce risk-based concentrations for 596 contaminants in air, drinking water, edible fish and soil. Because USEPA designed its methods to estimate upper bound risks, these risk-based concentrations are likely to be protective of human health. Regulatory officials can use this information to calculate numerical ratios between measured environmental levels and risk-based concentrations. These ratios serve as a surrogate for potential health impacts and can be used to prioritize problems for attention. Ratio calculation and ranking can be automated for searches of computerized environmental databases.


Structure and dynamics of human vimentin intermediate filament dimer and tetramer in explicit and implicit solvent models.
Intermediate filaments, in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, and play an important role in mechanotransduction as well as in providing mechanical stability to cells at large stretch. The molecular structures, mechanical and dynamical properties of the intermediate filament basic building blocks, the dimer and the tetramer, however, have remained elusive due to persistent experimental challenges owing to the large size and fibrillar geometry of this protein. We have recently reported an atomistic-level model of the human vimentin dimer and tetramer, obtained through a bottom-up approach based on structural optimization via molecular simulation based on an implicit solvent model (Qin et al. in PLoS ONE 2009 4(10):e7294, 9). Here we present extensive simulations and structural analyses of the model based on ultra large-scale atomistic-level simulations in an explicit solvent model, with system sizes exceeding 500,000 atoms and simulations carried out at 20 ns time-scales. We report a detailed comparison of the structural and dynamical behavior of this large biomolecular model with implicit and explicit solvent models. Our simulations confirm the stability of the molecular model and provide insight into the dynamical properties of the dimer and tetramer. Specifically, our simulations reveal a heterogeneous distribution of the bending stiffness along the molecular axis with the formation of rather soft and highly flexible hinge-like regions defined by non-alpha-helical linker domains. We report a comparison of Ramachandran maps and the solvent accessible surface area between implicit and explicit solvent models, and compute the persistence length of the dimer and tetramer structure of vimentin intermediate filaments for various subdomains of the protein. Our simulations provide detailed insight into the dynamical properties of the vimentin dimer and tetramer intermediate filament building blocks, which may guide the development of novel coarse-grained models of intermediate filaments, and could also help in understanding assembly mechanisms.


Space use by the endemic common (weedy) seadragon (Phyllopteryx taeniolatus): influence of habitat and prey.
The weedy seadragon (Phyllopteryx taeniolatus: Syngnathidae) is an iconic fish endemic to the southern coastal waters of Australia. The authors of this study analysed the habitat preferences and factors influencing microhabitat selection by P. taeniolatus in a population from Kurnell, NSW, Australia. Using field surveys and the resource selection probability function, the authors determined that P. taeniolatus significantly preferred kelp (Ecklonia radiata)-dominated habitat and avoided rock-dominated habitat. They showed P. taeniolatus preferred habitat of between 40% and 80% coverage of Ecklonia, while avoiding areas of <20% cover. Furthermore, across all habitats, mysid prey availability significantly influenced P. taeniolatus habitat selection. The strong dependence of P. taeniolatus on Ecklonia habitat shown in this study was previously untested and highlights that reductions in Ecklonia cover under climate change, or impacts from increasing urbanisation, may render seadragon populations vulnerable to declines.


Disinfection of various materials with 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride in hatchery facilities.
Surface disinfection is important in the proper running of livestock farms. However, disinfection of farm equipment and facilities is difficult because they are made of different materials, besides having large surface areas and complex structures. 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride (Si-QAC) is a quaternary ammonium salt-based disinfectant that attaches to various surfaces by forming covalent bonds and maintains its disinfecting capacity for a considerable time. Our aim was to evaluate the potential use of Si-QAC for disinfection of farm equipment and facilities. The short- and long-term antimicrobial and antiviral effects of Si-QAC were evaluated in both laboratory and farm settings using modified quantitative assessment method based on the standard operating procedures of the United States Environmental Protection Agency. Si-QAC was highly effective in controlling the growth of the Newcastle disease virus and avian pathogenic Escherichia coli. Electron microscopy revealed that the mechanism underlying the disinfection activity of Si-QAC was associated with its ability to damage the outer membrane of the pathogen cells. In the field test, Si-QAC effectively reduced viral contamination of surfaces of equipment and space. Our results suggest that Si-QAC has great potential as an effective chemical for disinfecting farm equipment and facilities. This disinfectant could retain its disinfection ability longer than other commercial disinfectants and contribute to better farm biosecurity.


Physical mapping of the human chromosome 11q23 region containing the ataxia-telangiectasia locus.
Two breakpoints within chromosome 11q23 were characterized with 29 DNA probes to establish a physical map of the region. This region is notable in that it contains at least 14 functional genes which are also syntenic in the mouse (chromosome 9). Chromosome 11q23 includes these markers: STMY, CLG, NCAM, DRD2, APOA1, APOC3, APOA4, CD3E, CD3D, CD3G, PBGD, THY1, ets-1, and cbl-2. The two breakpoints, herein called "X;11" and "4;11," defined a region of approximately 8 cM containing the APO and CD3 complexes as well as the polymorphic marker D11S29. DRD2 localized centromeric to the X;11 breakpoint despite evidence for close genetic linkage to D11S29, suggesting that DRD2 lies close to the X;11 breakpoint. THY1, PBGD, and cbl-2 localized telomeric to the 4;11 breakpoint and thus to the [D11S29--APO--CD3] grouping as well. The physical map helps to correlate the cytogenetic and linkage maps of this region. It also suggests that the human 11q23 syntenic grouping is inverted with respect to its murine counterpart. Based on this physical map and on our primary linkage map of the 11q23 region, we are able to confirm a preliminary localization of the gene for ataxia-telangiectasia group A (ATA) to a region centromeric to the interval defined by D11S144 (pYNB3.12) and THY1.


Characterization of micro-RNA in women with different ovarian reserve.
Women undergoing infertility treatment are routinely subjected to one or more tests of ovarian reserve. Therefore, an adequate assessment of the ovarian reserve is necessary for the treatment. In this study, we aimed to characterize the potential role of microRNAs (miRNAs) as biomarkers for women with different ovarian reserves. A total of 159 women were recruited in the study and classified according to their anti-Müllerian hormone (AMH) level into three groups: (1) low ovarian reserve (LAMH, n = 39), (2) normal ovarian reserve (NAMH, n = 80), and (3) high ovarian reserve (HAMH, n = 40). SurePrint Human miRNA array screening and reverse transcription-quantitative PCR (RT-qPCR) were respectively employed to screen and validate the miRNA abundance level in the three tested groups. Compared with NAMH, the abundance level of 34 and 98 miRNAs was found to be significantly altered in LAMH and HAMH, respectively. The abundance level of miRNAs was further validated by RT-qPCR in both, the screening samples as well as in an independent set of validation samples. The abundance levels of the validated miRNAs were significantly correlated with the AMH level. The best AUC value for the prediction of the increase and decrease in the AMH level was obtained for the miR-100-5p and miR-21-5p, respectively. The level of miRNAs abundance correlates with the level of AMH, which may serve as a tool for identifying women with a different ovarian reserve and may help to lay the ground for the development of novel diagnostic approaches.


Cognitive phenotype of mathematical learning disabilities: what can we learn from siblings?
The sensitivity of number sense as cognitive phenotype for mathematical learning disabilities (MLD) was assessed in siblings of children with MLD (n = 9) and age matched children without family members with MLD (n = 63). A number line estimation paradigm was used as a measure of children's early number sense. In line with the triple code model of Dehaene (1992), three different presentation formats were presented. The results of the study confirmed that number line estimation was related to early arithmetic achievement in kindergarten. In addition siblings were less proficient in number line placements compared to non-siblings, with a larger effect size for symbolic and especially number word estimation compared to the non-symbolic results. Siblings also differed from non-siblings on procedural and conceptual counting skills and logical thinking in kindergarten. Moreover MLD had a familial aggregation, since about three out of five sibling girls had clinical scores on an Early Numeracy Test in kindergarten, pointing to a risk to develop MLD themselves. Implications of the study to our understanding of MLD are discussed.


Griffonia simplicifolia negatively affects sexual behavior in female rats.
At present Griffonia simplicifolia is used in food supplement aimed to treat mood disorders as well as to reduce food intake and body weight. The plant has gained increasing interest for its high content in 5-hydroxy-L-tryptophan (5-HTP) particularly in the seed. The present study was designed to evaluate the influence of a seed extract of the plant, dosed at 25, 50 and 100 mg/kg, on the sexual behavior of ovariectomized hormone-primed rats after acute and subchronic treatment. The single administration of G. simplicifolia significantly reduced lordosis response and increased rejection behavior in female rats treated with the highest dose while it did not influence proceptive behaviors. On the other hand the subchronic administration of the extract significantly reduced proceptivity but not receptivity, and increased rejection behavior. All the tested dosages were able to markedly decrease food intake and body weight after a 9-day treatment. Taken together the present results, possibly ascribed to increased levels of 5-hydroxytryptamine (5-HT) in the brain, suggest a cautious administration of the plant extract owing to its negative influence on female sexual behavior.


The neural dynamics underlying the interpersonal effects of emotional expression on decision making.
Although numerous studies explore the effects of emotion on decision-making, the existing research has mainly focused on the influence of intrapersonal emotions, leaving the influence of one person's emotions on another's decisions underestimated. To specify how interpersonal emotions shape decision-making and delineate the underlying neural dynamics involved, the present study examined brain responses to utilitarian feedback combined with angry or happy faces in competitive and cooperative contexts. Behavioral results showed that participants responded slower following losses than wins when competitors express happiness but responded faster following losses than wins when cooperators express anger. Importantly, angry faces in competitive context reversed the differentiation pattern of feedback-related negativity (FRN) between losses and wins and diminished the difference between losses and wins on both P300 and theta power, but only diminished the difference on FRN between losses and wins in cooperative context. However, when partner displays happiness, losses versus wins elicited larger FRN and theta power in competitive context but smaller P300 in both contexts. These results suggest that interpersonal emotions shape decisions during both automatic motivational salience valuation (FRN) and conscious cognitive appraisal (P300) stages of processing, in which different emotional expressions exert interpersonal influence through different routes.


Two new rapid PCR-based methods for identification of Acinetobacter baumannii isolated from clinical samples.
The accurate identification of Acinetobacter spp. is challenging due to their high phenotypic and biochemical similarities. Because clinical relevance and antibiotic susceptibility are significantly different among different genomic species of Acinetobacter, the exact identification of A. baumannii is necessary and it can help us prevent inappropriate antibiotic use and inferior clinical care. This project employed a sequence-specific PCR assay for the rpoB region in A. baumannii to distinguish it from non-Acinetobacter baumannii Acinetobacter species. Moreover, a duplex PCR assay was used to detect blaOXA-51-like and gluconolactonase genes as a second identification method. In this study, 210 isolates of Acinetobacter spp. were considered and identified by PCR-sequencing of rpoB gene as a reference test. PCR-sequencing of rpoB revealed that 179 isolates were A. baumannii and 31 were non- A. baumannii Acinetobacter strains. PCR amplification targeting the rpoB gene as the first method, detected 182 isolates of A. baumannii, while duplex PCR assay confirmed 163 isolates as A. baumannii. Data analysis indicated that the sensitivities of sequence-specific PCR of the rpoB gene and duplex PCR assay were 100% and 91.06%, respectively, while specificities were 91.18% and 100%, respectively. Given the data, it was revealed that these two methods showed a reasonable potential for the accurate identification of A. baumannnii from non- A. baumannii species. Sequence-specific PCR assay for the rpoB gene and duplex PCR assay for blaOXA-51-like and gluconolactonase genes are rapid, reliable and cost-effective methods which can be used in clinical laboratories for the accurate identification of A. baumannii.


Effective radiation attenuation calibration for breast density: compression thickness influences and correction.
Calibrating mammograms to produce a standardized breast density measurement for breast cancer risk analysis requires an accurate spatial measure of the compressed breast thickness. Thickness inaccuracies due to the nominal system readout value and compression paddle orientation induce unacceptable errors in the calibration. A thickness correction was developed and evaluated using a fully specified two-component surrogate breast model. A previously developed calibration approach based on effective radiation attenuation coefficient measurements was used in the analysis. Water and oil were used to construct phantoms to replicate the deformable properties of the breast. Phantoms consisting of measured proportions of water and oil were used to estimate calibration errors without correction, evaluate the thickness correction, and investigate the reproducibility of the various calibration representations under compression thickness variations. The average thickness uncertainty due to compression paddle warp was characterized to within 0.5 mm. The relative calibration error was reduced to 7% from 48-68% with the correction. The normalized effective radiation attenuation coefficient (planar) representation was reproducible under intra-sample compression thickness variations compared with calibrated volume measures. Incorporating this thickness correction into the rigid breast tissue equivalent calibration method should improve the calibration accuracy of mammograms for risk assessments using the reproducible planar calibration measure.


Modular barcode beads for microfluidic single cell genomics.
Barcode beads allow efficient nucleic acid tagging in single cell genomics. Current barcode designs, however, are fabricated with a particular application in mind. Repurposing to novel targets, or altering to add additional targets as information is obtained is possible but the result is suboptimal. Here, we describe a modular framework that simplifies generation of multifunctional beads and allows their easy extension to new targets.


CircATRNL1 promotes epithelial-mesenchymal transition in endometriosis by upregulating Yes-associated protein 1 in vitro.
Endometriosis is a common and benign gynecological disorder but exhibits malignant features. However, the underlying pathogenesis and pathophysiology of endometriosis remain unclear. Circular RNAs have been demonstrated to participate in the occurrence and progression of multiple diseases. This study was aimed to explore the roles of circATRNL1 in endometriosis in vitro. Based on the results of reverse transcription-quantitative polymerase chain reaction analysis, we found significant upregulation of circATRNL1 and Yes-associated protein 1 (YAP1), while downregulation of miR-141-3p and miR-200a-3p in ectopic tissues compared to eutopic tissues. The immunohistochemistry and western blot analysis showed differentially expressed epithelial-mesenchymal transition (EMT) markers between EuEM and EcEM tissues. The in vitro assays indicated that overexpression of circATRNL1 could promote the proliferation, migration, and invasion of Ishikawa cells, and induce EMT process, while circATRNL1 silencing showed the opposite effect. The mechanical investigation indicated that circATRNL1 upregulated YAP1 by sponging miR-141-3p and miR-200a-3p. Gain-of-function assays validated the inhibitory function of miR-141-3p and miR-200a-3p in endometriosis. The results of rescue assays confirmed the function of circATRNL1-miR-141-3p/miR-200a-3p-YAP1 axis on Ishikawa cells. Our findings demonstrate that abnormal upregulation of circATRNL1 regulates cell proliferation and motility and promotes EMT process via the miR-141-3p/miR-200a-3p-YAP1 axis in vitro, which could contribute to the progression of endometriosis.


Fungal deterioration of melon seeds stored in jute sacks and polyethylene bags in Ago-Iwoye, southwestern Nigeria.
Laboratory studies were carried out in the Department of Biological Sciences, Ogun State University, Ago-Iwoye, southwestern Nigeria, to determine the extent of fungal deterioration of melon seeds stored in two types of storage bags viz; jute and polyethylene bags. Melon seeds of varieties Tc139 and V2 were stored in jute and polyethylene bags under ambient conditions using the 2 x 2 factorial design (variety vs type of bag) for 12 months. The moisture content (mc), incidence of visible mouldiness (ivm) and germinability of the stored seeds were determined monthly. The mc of Tc139 ranged from 6.1 to 6.7% in jute and 6.2 to 6.5% in polyethylene bags. The ivm which was initially 2.1% increased to 10.7% and 5.5% in jute and polyethylene bags respectively, after 12 months in storage. The germination percentage decreased from 96.3% to 28.7% and 45.3% in jute and polyethylene bags, respectively. The mc of V2 stored in jute and polyethylene bags varied from 5.9 to 6.4%, and 5.8 to 6.2%, respectively. The ivm increased from 1.8% before storage to 8.9% and 4.8% in jute and polyethylene bags, respectively, after 12 months. The percentage seed germination declined from 98.0% to 37.3% in jute and 48.7% in polyethylene bags after 12 months. Decreased incidence of field fungi namely: Alternaria,Botryodiplodia theobromae, Cladosporium, Fusarium and Macrophomina phaseolina was accompanied by simultaneous increase in storage fungi viz: Aspergillus, Penicillium, and Rhizopus with prolonged storage.


A Bibliometric Analysis on Global Psychological and Behavioral Research Landscape on COVID-19 Pandemic.
The COVID-19 pandemic outbreak in December 2019 has spread globally. The ongoing psychological and behavioral effects of the COVID-19 pandemic, which poses a major challenge to humanity, are of concern to researchers. To understand the academic community's attention, focus and research collaboration on psychological and behavioral research during the COVID-19 pandemic, we conducted a macro analysis using a bibliometric approach. Using the topic selection strategy of TS = ("COVID-19" OR "coronavirus disease 2019" OR "SARS-CoV-2" OR "2019-nCoV") AND TS = ("behavio*") AND TS = ("psycholog*"), 2096 high-quality research articles and reviews were downloaded as data from the Web of Science core collection on 16 November 2021. Through analysis and visualization, the following conclusions are drawn in this study: (1) The popularity and importance of psychological and behavioral research under COVID-19 has increased significantly and needs further attention; (2). Related research focuses on eight hotspots, with quarantine, health care workers, the elderly, students, pregnant women, family, consumers, social media and emergency preparedness knowledge as the focus of the research object; and (3) Research collaboration is relatively high at the author, organizational and national levels. However, low-income countries need to get more attention. Furthermore, this article would help researchers make decisions for the research of psychological and behavioral issues under COVID-19 and planning for future prospects to contribute to academic development and applied methodology.


Further simplification of the Guizotia abyssinica seed medium for identification of Cryptococcus neoformans and Cryptococcus bacillispora.
A simplified Guizotia abyssinica seed-based medium for presumptive diagnosis of Cryptococcus neoformans and C. bacillispora (Paliwal and Randhawa 1978) was further simplified by replacing seed extract with pulverized seeds. This medium gives unambiguous results, avoids false-positive reactions with 13 other yeastlike organisms, and is simple and relatively inexpensive to prepare.


Crystallization and preliminary X-ray diffraction study of an endoglucanase from Clostridium thermocellum.
Endoglucanase D, a cellulose degradation enzyme from Clostridium thermocellum has been cloned in Escherichia coli, purified and crystallized. The crystals are trigonal, space group P3(1)12 (or P3(2)12) with a = 57.7 (+/- 0.1) A, c = 192.1 (+/- 0.2) A, and diffract X-rays to a resolution of 2.8 A. They are suitable for a high-resolution X-ray diffraction analysis.


Electronic retinal prosthesis for severe loss of vision in geographic atrophy in age-related macular degeneration: First-in-human use.
To date there are yet no available approved therapies for Geographic Atrophy (GA) secondary to age-related macular degeneration (AMD). Single site, non-randomized safety and efficacy study presenting the preliminary results in a cohort of five late stage AMD (GA) patients successfully implanted with the Argus II Retinal Prosthesis System (Second Sight Medical Products Inc., Sylmar, CA, USA). Extensive fundus imaging including retinal photographs from which the GA area was measured. A combination of custom and traditional tests designed for very low vision subjects assessed visual function in study subjects. A Functional Low-Vision Observer Rated Assessment was carried out to evaluate the impact of the system on the subject's daily life. In addition, a study to evaluate structural characteristics of the visual cortex of the brain was performed in one subject using magnetic resonance imaging. Seven device-related adverse events were reported, four of which were classed as serious adverse events. Retinal detachment was reported in three patients and was successfully treated within 12 months of onset. Testing showed an improvement in visual function in three of five patients with the system turned on. Magnetic resonance imaging assessed in one patient after implantation indicates a selective increase in cortical myelin and thickness in visual brain regions 1 year post implantation. Epiretinal prostheses can successfully be implanted in those affected by GA secondary to late-stage AMD and can elicit visual percepts by electrical stimulation of residual neuroretinal elements and improve basic visual function in those affected.


Mechanisms underlying the asynchronous replacement of myosin light chain isoforms during stimulation-induced fibre-type transformation of skeletal muscle.
During the fibre-type transformation induced by chronic electrical stimulation of rabbit fast-twitch muscle, replacement of the fast forms of the two classes of myosin light chain by their slow isoforms occurs asynchronously. Studies of total cellular myosin light chains and of the slow-to-fast transition now justify the conclusion that the asynchrony is due to switching between the expression of fast and slow genes for the two light chain classes at sequential stages of the transformation process.


Validation of the modified American Urological Association symptom score.
We created a shorter version of the American Urological Association symptom score, called UWIN (urgency, weak stream, incomplete emptying and nocturia). Participants in Prostate Cancer Awareness Week from 2006 and 2007 were administered the regular American Urological Association symptom score and UWIN. A total of 278 participants completed each questionnaire. Total scores of each participant for the American Urological Association symptom score (range 0 to 35) and UWIN (range 0 to 12) were evaluated using Spearman's correlation coefficients and Bland-Altman plots to determine the level of agreement between the 2 questionnaires. The correlation between the total American Urological Association symptom score (range 0 to 35) and the total UWIN score (range 0 to 12) was 0.913 (p<0.0001). The correlation between the quality of life question on the American Urological Association symptom score and UWIN was 0.821 using the Spearman correlation coefficient (p<0.0001). A second analysis performed using Bland-Altman plots showed good agreement between the American Urological Association symptom score and UWIN. Overall, respondents tended to have slightly higher UWIN total scores than their American Urological Association symptom scores. This study validates that the UWIN questionnaire can be used in place of the American Urological Association symptom score. The UWIN questionnaire will lessen the burden on the respondent, broaden the applicability of the instrument and make collecting data as efficient and effective as possible.


Buttock claudication from isolated stenosis of the gluteal artery.
Buttock claudication is usually caused by proximal arterial obstruction in the aorta or the common iliac artery. We report an unusual case of buttock claudication caused by isolated stenosis of the superior gluteal artery diagnosed by angiography. Both physical examination and noninvasive vascular explorations had been unremarkable. Twenty-six months after undergoing treatment by percutaneous transluminal angioplasty, the patient has no symptoms. Buttock claudication related to unilateral stenosis of the superior gluteal artery as observed in this case can be successfully managed by percutaneous transluminal angioplasty.


Complete uterine septum involving cervix with unilateral external cervical os stenosis: diagnosis and management.
Congenital external cervical os stenosis is a form of Mullerian duct abnormality which is rare in virginal adolescents. Pre-operatively, two non-sexually active adolescents of 12 and 14 years of age, with history of light menses and severe lower abdominal pain for 2 and 4 months respectively, were diagnosed with an obstructed, oblique vaginal septum syndrome. However, at operative vaginoscopy, a single cervix with a duplicated cervical os and unilateral cervical stenosis was discovered, confirming the diagnosis of a complete uterine septum involving the cervix and unilateral cervical stenosis. They were treated by expanding the affected external cervical os while leaving the hymen intact. A year following the treatment, follow up results found no recurrence of symptoms. Operative vaginoscopy using a hysteroscope is crucial and recommended for the diagnosis and treatment of congenital external cervical os stenosis in virginal adolescents.


Differential immunohistochemical resolution of the human mononuclear phagocyte system.
Four new monoclonal antibodies, termed Ki-M1, Ki-M2, Ki-M3, and Ki-M4, were developed for distinguishing macrophage subgroups. Purified lysosomes of cells of stimulated U-937 cell line were used as immunogen. Specificity control was performed by staining unfixed cryostat sections of fresh human tissue with an immunohistochemical method, which allowed reliable recognition of reactive structures. Ki-M1 reacted with macrophages of lymphoid tissue, lung, and serous cavities. Ki-M2 recognized Kupffer cells and splenic macrophages. Both monoclonal antibodies reacted with interdigitating reticulum cells and Langerhans cells, which are thought to be accessory cells of the T-cell immune response. Accessory cells of the B-cell immune response, on the other hand, showed reactivity with Ki-M3 and Ki-M4. Thus, analogous to T lymphocytes, the human mononuclear phagocyte system (MPS) can be subdivided into different subgroups with the aid of appropriate monoclonal antibodies.


In silico prediction of COVID-19 cytokine storm in lung cancer types.
Lung cancer is one of the most frequently diagnosed malignant tumors and the leading cause of cancer-related death worldwide. Mainly, Non-small-cell lung cancer (NSCLC), which accounts for more than eighty-five percent of all lung cancers, consists of two major subtypes: lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Novel coronavirus disease (COVID-19) affected millions of people caused by acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) around the globe. Lung cancer patients and COVID-19 present unique and unfortunate lethal combinations because the lungs are the primary target organ of SARS-CoV-2 infection. Clinical studies have demonstrated that an over-activated inflammatory response associated with severe COVID-19 cases is characterized by excessive auto-amplifying cytokine release, which is defined as a "cytokine storm." ACE2 and TMPRSS2 receptors play an essential role in SARS-CoV-2 infection; therefore, using in silico analysis, we did correlation analysis with immune infiltration markers in LUAD and LUSC patient groups. Our study identified a promising correlation between immune-modulators and receptor proteins (ACE-2 and TMPRSS2), creating a domain that requires further laboratory studies for clinical authentication.


Regulation of Ca2+ transport in brain mitochondria. II. The mechanism of the adenine nucleotides enhancement of Ca2+ uptake and retention.
ADP greatly enhances the rate of Ca2+ uptake and retention in Ca2+ loaded mitochondria. Atractyloside, a specific inhibitor of the ADP/ATP translocator, completely inhibits the ADP effect, while bongkrekate, another specific inhibitor of the translocator enhances the effect of ADP. These results indicate that locking the ADP/ATP translocator in the M-state is sufficient to produce the ADP effect. Cyclosporin A, a specific inhibitor of the Ca2(+)-induced membrane permeabilization does not substitute for ADP, indicating that ADP directly affect the rate of electrogenic Ca2+ uptake. The effect of the translocator conformation on the rate of electrogenic Ca2+ uptake is independent of the concentration of Pi and is not caused by changes in membrane potential. However, locking the carrier in the M-state appears to increase the negative surface charge on the matrix face of the inner membrane. This may lead to an enhanced rate of Ca2+ dissociation from the electrogenic carrier at the matrix surface. The rate of Na(+)-independent Ca2+ efflux is only slightly inhibited by locking the carrier in the M-state, presumably due to the same mechanism. In the presence of ADP, Pi inhibits the Na(+)-independent efflux. In the presence of physiological concentrations of spermine, Pi and Mg2+, the rate of Ca2+ uptake, Ca2+ retention and Ca2+ set points depend sharply on ADP concentration at the physiological range of ADP. Thus, changes of cytosolic ADP concentration may lead to change in the rate of Ca2+ uptake by mitochondria and thus modulate the excitation-relaxation cycles of cytoplasmic free calcium.


Efficacy of commercial soft contact lens disinfectant solutions against Acanthamoeba.
To investigate the relative efficacy of Japanese commercial soft contact lens disinfectant solutions against Acanthamoeba trophozoites and cysts. Eight types of multipurpose solution (MPS), two types of hydrogen peroxide solution, and one povidone-iodine solution were evaluated to determine their effect against Acanthamoeba trophozoites and cysts (ATCC 50514). Acanthamoeba cysts were cultured in encystment medium for either 1 or 2 weeks (1 and 2-week-old cysts). The trophozoites and cysts were treated with each disinfectant solution for 0, 2, 4, 8, or 24 h. After performing four tenfold serial dilutions of each test solution, dilutions were cultured for 10 days. The number of surviving organisms was calculated using the trimmed Spearman-Karber method. Among the MPS tested, only four were effective against trophozoites after treatment for 4 h, and none was effective against 2-week-old cysts. Hydrogen peroxide had a significant effect on trophozoites and 1-week-old cysts, but not on 2-week-old cysts. In contrast, povidone-iodine caused a 2.6 log reduction in 2-week-old cysts. MPS were found to have limited efficacy against trophozoites and no efficacy against 2-week-old cysts. Only povidone-iodine had any efficacy against 2-week-old cysts.


Impact of Staphylococcus aureus Small Colony Variants on Human Lung Epithelial Cells with Subsequent Influenza Virus Infection.
Human beings are exposed to microorganisms every day. Among those, diverse commensals and potential pathogens including Staphylococcus aureus (S. aureus) compose a significant part of the respiratory tract microbiota. Remarkably, bacterial colonization is supposed to affect the outcome of viral respiratory tract infections, including those caused by influenza viruses (IV). Since 30% of the world's population is already colonized with S. aureus that can develop metabolically inactive dormant phenotypes and seasonal IV circulate every year, super-infections are likely to occur. Although IV and S. aureus super-infections are widely described in the literature, the interactions of these pathogens with each other and the host cell are only scarcely understood. Especially, the effect of quasi-dormant bacterial subpopulations on IV infections is barely investigated. In the present study, we aimed to investigate the impact of S. aureus small colony variants on the cell intrinsic immune response during a subsequent IV infection in vitro. In fact, we observed a significant impact on the regulation of pro-inflammatory factors, contributing to a synergistic effect on cell intrinsic innate immune response and induction of harmful cell death. Interestingly, the cytopathic effect, which was observed in presence of both pathogens, was not due to an increased pathogen load.


Upgrade Rates of Pure, Radiology-Pathology Concordant Lobular Neoplasia Diagnosed on Breast Core Needle Biopsy: Is Surgical Excision Warranted?
To determine upgrade rates of lobular neoplasia (LN) to malignancy and evaluate factors that may predict upgrade. From 5/1/2003 to 12/30/2015, breast lesions diagnosed as LN (atypical lobular hyperplasia [ALH] or classic lobular carcinoma in-situ [LCIS]) on core biopsy that underwent surgical excision or at least 2 years imaging follow-up were identified. A subspecialty trained breast radiologist and pathologist reviewed imaging and pathology slides to confirm diagnosis and to determine if LN represented the target lesion, part of the target lesion, or an incidental finding. Imaging features, original BI-RADS final assessment category, biopsy method, biopsy device and final pathologic diagnosis were documented. Cases with both ALH and LCIS were classified as LCIS for analysis. Reason for biopsy of BI-RADS 2-3 was patient or referring physician preference. Upgrade rates to malignancy were determined for all cases. In this study 73.7% (115/156) lesions were ALH and 26.3% (41/156) were LCIS+/-ALH. Surgical excision and imaging follow-up were performed in 71.2% (111/156) and 28.8% (45/156), respectively. Upgrade rates for ALH and LCIS were 0.0% (0/115) and 7.3% (3/41), respectively. Cancer developed at a site separate from core biopsy in 1.7% (2/115) ALH and 7.3% (3/41) LCIS cases. We found no association of upgrade rate with biopsy type, BI-RADS or target/part of target lesion versus incidental. Our study supports consideration of excision for LCIS, given 7.3% upgrade rate. Conversely, imaging surveillance might be appropriate following diagnosis of ALH alone.