Effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) on weight loss and biomarker parameters in morbidly obese patients: a 12-month follow-up.
Laparoscopic Roux-en-Y gastric bypass (LRYGB) is suggested as the gold standard of the surgical techniques for morbid obesity treatment. The aim of this study was to evaluate the weight loss and biomarker parameter changes over a 1-year period following LRYGB in Iranian morbidly obese patients. Sixty patients who had undergone LRYGB from June 2006 to August 2008 were followed up. Complication rates and changes in anthropometric indices, metabolic parameters, and obesity-related comorbidities were evaluated. During the mean follow-up duration of 27.2 ± 9.4 months, the mean weight reduced from 128.8 ± 20.4 to 86.9 ± 12.7 kg with excess weight loss (%EWL) of 63.8 ± 15.6%. The male young-adolescent patients showed more weight loss than females. Biochemical parameter changes were reduction of fasting blood sugar by 19%, total cholesterol by 17%, triglyceride by 30%, low-density lipoprotein by 19%, aspartate aminotransferase by 44%, alanine aminotransferase by 52%, alkaline phosphatase by 33%, and uric acid by 19%, while high-density lipoprotein (HDL) levels increased by 22%. HDL level change was the only biomarker factor showing correlation with age (P = 0.005, r = -0.353, R(2) = 0.125). Obesity comorbidities were resolved considerably. There were two cases of surgical complications and no case of mortality. LRYGB appears to be a safe and effective procedure with a low complication rate in Iranian morbidly obese patients. It results in weight loss, reduction in obesity comorbidities, increasing HDL, and decreasing other measured plasma biochemical parameters. Based on our results, we suggest that LRYGB would benefit young male morbidly obese patients more than others.


Role of vitamin D in the association between pre-stroke sleep quality and poststroke depression and anxiety.
Poor sleep quality, mood disorders, and vitamin D deficiency are common in stroke. We investigated the association between serum vitamin D levels and pre-stroke sleep quality and the occurrence of poststroke depression (PSD) and poststroke anxiety (PSA) in acute ischemic stroke (AIS). This prospective cross-sectional study included hospitalized patients with AIS and age- and sex-matched controls. Vitamin D levels were measured within 24 h of admission. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) at admission. The severity of depression and anxiety symptoms was evaluated according to Beck Depression Inventory and Beck Anxiety Inventory scores, respectively, within 72 h after admission. Comparing 214 AIS patients with 103 controls, patients had significantly higher scores of Beck Depression Inventory, Beck Anxiety Inventory, and PSQI and lower vitamin D levels (p < 0.001). Among AIS patients, Beck Depression Inventory (p = 0.004) and Beck Anxiety Inventory (p = 0.018) scores were significantly higher in bad sleepers (PSQI score ≥ 6) than in good sleepers (PSQI score ≤ 5). Correlation analysis revealed negative correlations between serum vitamin D levels and Beck Depression Inventory (r = - 0.234; p < 0.001), Beck Anxiety Inventory (r = - 0.135; p = 0.016), and PSQI (r = - 0.218; p < 0.001) scores. Decreased serum vitamin D levels at admission are associated with a high risk for PSD and PSA in patients with poor pre-stroke sleep quality during the early stages of AIS.


Streptavidin Fe2O3-gold nanoparticles functionalized theranostic liposome for antibiotic resistant bacteria and biotin sensing.
Novel methods of sensing and treatment required to elicit potent humoral and cellular immune responses. Here, Streptavidin functionalized α-Fe2O3-Au nanoparticles (STV-Mag) loaded cationic carbomate cholesterol is used as a carrier to release antibacterial thymol drug for Staphylococcus aureus (S. aureus) infected Caenorhabditis elegans (C. elegans). Pertaining to theranostic applications, efficient antimicrobial activity, and non-stimulated drug release and biotin dependent S. aureus growth were studied in-vivo. While STV-Mag was tethered on mercaptobenzoic acid (MBA) molecular cushion for label free streptavidin-biotin electrochemical sensing, the STV-Mag-carbomate cholesterol (STV-Mag-cCHOL liposome) vesicle with loaded drug was tethered on MBA for non-stimulant drug release through specific cholesterol-S. aureus interaction and confirmed electrochemically. Selectivity was confirmed using other pathogens, E. coli, Proteus and Enterococcus bacterium through antimicrobial studies along with S. aureus. The biotin sensing showed linear range from 10-15 to 10-3 M, which was not obtained by conventional methods. Fourier-Transform Infra-red (FT-IR), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) techniques were used to characterize the nanoparticulate system.


In silico analyses and design of chimeric proteins containing epitopes of Bartonella henselae antigens for the control of cat scratch disease.
Bartonella henselae is a Gram-negative bacterium that causes cat scratch disease (CSD), as well as bacteremia, endocarditis, and other clinical presentations. CSD remains one of the most common infections caused by bacteria in the genus Bartonella, and it is transmitted to humans through a scratch or cat bite. Vaccination and more efficient diagnostic methods would represent a promising and sustainable alternative measure for CSD control in humans and animals. Here, we described the in silico analyses and design of three recombinant chimeric proteins (rC1, rC2, and rC3), for use in the control of CSD. The chimeras were constructed with epitopes identified from the sequences of the GroEL, 17 kDa, P26, BadA, Pap31, OMP 89, and OMP 43, previously described as the most important B. henselae antigens. The rC1, rC2, and rC3 were expressed and purified using a heterologous system based on Escherichia coli and reacted with antibodies present in the sera of humans naturally infected. The chimeric proteins were used to immunize mice using Freund adjuvant, and the humoral immune response was evaluated. Animals immunized with rC1 and rC3 showed a significant IgG antibodies response from the 28th day (P < 0.05), and the animals immunized with the rC2 from the 35th day (P < 0.05) remained until the 56th day of experimentation, with a titer of 1:3200 (P < 0.05), 1:1600 (P < 0.05) and 1:1600 (P < 0.05) from rC1, rC2, and rC3, respectively. Significant production of IgA and IgG1 isotype was detected in animals immunized with rC1 and rC2 proteins. Additionally, analysis using 13 serum samples from naturally infected patients showed that the proteins are recognized by antibodies present in sera, reinforcing the possibility of using these chimeras for CSD control. KEY POINTS: • The recombinant chimeras were expressed in Escherichia coli with 37 kDa (rC1), 35 kDa (rC2), and 38 kDa (rC3). • Animals immunized with rC1, rC2, and rC3 showed significant antibody response. • The chimeras were recognized by the sera of naturally infected patients.


Localization of calbindin D-28K in the otoconia of lizard Podarcis sicula.
The membranous labyrinth of lizard Podarcis sicula contains calcite and aragonite crystals. Saccule, utricle and lagena contain calcite crystals while aragonite crystals are present only in the saccule where they are very abundant. We have recently demonstrated the presence of calbindin D-28K in the organic matrix of lizard P. sicula otoconia. In order to define its localization, since calbindin modulates cellular Ca2+ level, otoconia from utricle and lagena were collected separately from those from saccule and then otoconial proteins were extracted. Immunoblot assay on proteins extracted from the otoconia and confocal laser scanning microscope analyses of otoconia using monoclonal anti-calbindin D-28K antibodies indicated that calbindin D-28K is a protein typical of aragonite crystals.


Proactive Geriatric Comanagement of Nursing Home Patients by a New Hospital-Based Liaison Geriatric Unit: A New Model for the Future.
During the SARS-CoV-2 pandemic, hospital-based liaison geriatric units (LGUs) were created in Spanish hospitals with the aim to improve health care coordination between nursing homes (NHs) and hospitals. Our university hospital created a comprehensive, proactive LGU serving 31 public and private NHs of different sizes and characteristics to offer support to more than 2500 residents. In the first 3 months of 2021, this LGU performed 1252 assessments (81% as outpatients, 12% at the emergency department, and 7% during hospitalization), avoiding an estimated 49 hospital transfers and 29 hospitalizations. Other activities included giving NHs support and advice during COVID-19 outbreaks, comanagement of selected residents with other hospital-based specialists (implementing telemedicine), and implementation of a protocol that allowed using drugs only approved for hospital use in selected NHs. This model of LGU has been shown to be feasible, to improve residents' health care, and avoid hospital referrals. Long-term care needs to be re-imagined, and hospital geriatric departments need to prove that they are able to offer expertise to support NH health care professionals.


[Polyradiomodification. Combined body protection in the total irradiation of mice during exogenous hypoxia].
A high efficacy of the combined use of nontoxic doses of two pharmaceuticals: cystamine (50 mg/kg) and mexamine (25 mg/kg) under the conditions of short-term exogenous hypoxia (7.5% O2) was found in (CBA X C57Bl)F1 mice. The dose modification factor using the survival rates was 2.56.


A new histamine metabolite, quantitatively important in chicken.
After i.v. injection of 14C-histamine to chicken, we identified one of the histamine metabolites as N-acetylmethylhistamine in the urine. This new metabolite accounted for about 20% of the urinary or 14% of the administered radioactivity.


Excessive Body Weight and Diverticular Disease.
The worldwide proportion of overweight adults almost doubled from 22% in 1975 to 39% in 2016. Comparably, for the USA and Germany in 2016, the proportion was 68 and 56.8%, respectively. In Olmsted County, Minnesota, the prevalence of diverticulitis also doubled between 1980 and 2007, from 19 to 40%. Obesity substantially increases the risk of multiple gastrointestinal (GI) diseases and non-GI diseases. In a narrative review, we examined the evidence on whether obesity also increases the risk for the development of diverticulosis or diverticular disease and its outcome. Evidence suggests that being overweight (body mass index ≥25 kg/m2) or obese (≥30 kg/m2), especially viscerally obese, is a risk factor for diverticulosis, diverticular disease and diverticulitis, diverticular bleeding, more severe or complicated disease, recurrent disease, and for worse outcomes after surgery. There is a well-founded association between overweight and diverticular disease as well as diverticulosis. It is not clear whether overweight per se or confounders linked with it are responsible for the association. However, means to fight the overweight and obesity epidemic might also help to reduce the prevalence of morbidity and mortality from diverticular disease.


[Traditional Chinese Medicine Treatment of Gouty Arthritis Based on Syndrome Differentiation].
To observe the clinical effect and safety of traditional Chinese medicine (TCM) treatment in gouty arthritis (GA) based on syndrome differentiation. 81 patients of GA were enrolled from August 2013 to August 2014. They were divided into syndrome differentiation treatment group (27 cases), disease differentiation treatment group (27 cases) and basic treatment group (27 cases). The patients in syndrome differentiation treatment group were given corresponding TCM drug granules prescription by dialectical syndromes classification. The patients in disease differentiation treatment group were given TCM drug granules prescription. The patients in basic treatment group.were only given Diclofenac Sodium sustained-release tablets in acute phase, and Benzbromarone tablets in chronic phase. After 12 weeks treatments, all the patients received the measurements of serum uric acid (SUA), serum creatinine (SCr), blood urea nitrogen (BUN), triacylglycerol (TG), cholesterol (TC). The clinical efficacy, recurrence rate and adverse reactions were recorded and analyzed. Syndrome differentiation treatment group achieved higher clinical efficacy than basic treatment group and disease differentiation treatment group (P<0. 05). Moreover, syndrome differentiation treatment were superior to disease differentiation treatment in improving of recurrence rate (P<0. 05). There were no obvious adverse reactions occurred. There were no clinical significant changes in blood, urine routine analysis, and electrocardiogram examination before and 3 months after the treatments. The treatment of TCM in patients with GA based on syndrome differentiation showed definite therapeutic effects.


Best Practices for FACE-Q Aesthetics Research: A Systematic Review of Study Methodology.
The FACE-Q Aesthetics module is a validated patient-reported outcome measure (PROM) that evaluates perspectives on facial aesthetic treatments. Improper administration and poor study methodology can compromise the validity and interpretation of this PROM. This systematic review sought to evaluate the administration and scoring of the FACE-Q Aesthetics scales within the literature. A search of Ovid Medline, Embase, Cochrane, and Web of Science was performed on December 20, 2022, with the assistance of a health-research librarian (CRD42022383676). Studies that examined facial aesthetic interventions using the FACE-Q Aesthetics module as a primary or secondary outcome measure were included for analysis. There were 114 studies included. The Face Overall (n = 52, 45.6%), Psychological (n = 45, 39.4%), and Social (n = 43, 37.7%) scales were most frequently reported. Errors in FACE-Q administration were identified in 30 (26.3%) studies. The most common error was the presentation of raw ordinal scores rather than the converted Q score (n = 23). Most studies reported a time horizon for their primary analysis (n = 76, 66.7%); however, only 4 studies provided a rationale for this selection. Sample size calculations for the primary outcome were rarely performed (n = 9, 7.9%). There continues to be limitations in PROM administration and the quality of articles that report FACE-Q Aesthetic scale data. The authors suggest that future investigators using the FACE-Q refer to the User's Guide regarding administration and scoring of this scale, report a rationale for the study time horizon, and provide an a priori sample size calculation for the primary outcome of interest.


Sex Differences in the Clinical Outcomes After Left Atrial Appendage Closure: A Systematic Review and Meta-Analysis.
Left atrial appendage occlusion (LAAO) has emerged as a reasonable alternative to oral anticoagulation in a selective group of patients with atrial fibrillation (AF). While women are known to have higher risk of AF-related stroke, the impact of sex differences on the clinical outcomes of LAAO has not been well-studied. We sought to perform a meta-analysis evaluating sex differences on the outcomes of patients undergoing LAAO. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases (from inception to October 2021) for studies evaluating the impact of sex difference on LAAO procedural outcomes. We used a random-effects model to calculate risk ratio (RR) with 95% confidence intervals (CI). In-hospital all-cause mortality and ischemic stroke were the primary endpoints. In-hospital pericardial effusion/cardiac tamponade, major bleeding, technical success, device-related thrombus, and hospital length of stay were secondary outcomes. A total of 5 studies with 54,754 patients were included, of whom 22,461 (41%) were females. Female sex was associated with higher rates of in-hospital all-cause mortality (RR 2.18; 95% CI 1.46-3.26; P = 0.0001) and in-hospital ischemic stroke (RR 1.67; 95% CI 1.06-2.61; P = 0.03) when compared with males. Females had higher rates of in-hospital major bleeding (RR 1.93; 95% CI 1.40-2.67; P < 0.0001) and hospital length of stay >1 day (RR 1.38; 95% CI 1.33-1.45; P < 0.00001). There were no differences between females and males in terms of technical success (RR 1.00; 95% CI 1.00-1.00; P = 1.00) and device-related thrombus and (RR 0.94, 95% CI 0.31-2.82; P = 0.91). Women are more likely to experience worse periprocedural outcomes with longer hospital stay after LAA closure. Further efforts are needed to increase the participation of women in clinical studies and to assess these differences to properly address the discrepancy in outcomes between men and women.


Circadian CLOCK Mediates Activation of Transforming Growth Factor-β Signaling and Renal Fibrosis through Cyclooxygenase 2.
The circadian rhythm regulates blood pressure and maintains fluid and electrolyte homeostasis with central and peripheral clock. However, the role of circadian rhythm in the pathogenesis of tubulointerstitial fibrosis remains unclear. Here, we found that the amplitudes of circadian rhythm oscillation in kidneys significantly increased after unilateral ureteral obstruction. In mice that are deficient in the circadian gene Clock, renal fibrosis and renal parenchymal damage were significantly worse after ureteral obstruction. CLOCK-deficient mice showed increased synthesis of collagen, increased oxidative stress, and greater transforming growth factor-β (TGF-β) expression. TGF-β mRNA expression oscillated with the circadian rhythms under the control of CLOCK-BMAL1 heterodimers. The expression of cyclooxygenase 2 was significantly higher in kidneys from CLOCK-deficient mice with ureteral obstruction. Treatment with a cyclooxygenase 2 inhibitor celecoxib significantly improved renal fibrosis in CLOCK-deficient mice. Taken together, these data establish the importance of the circadian rhythm in tubulointerstitial fibrosis and suggest CLOCK/TGF-β signaling as a novel therapeutic target of cyclooxygenase inhibition.


Midwives holding the space for women undergoing termination of pregnancy: A qualitative inquiry.
Hospital midwives are the main care givers for women undergoing termination of pregnancy after 20 weeks. Midwives' role and potential impact of regular involvement in termination of pregnancy (TOP) are poorly understood. New Zealand. TOP after 20 weeks may be performed to save a woman's life or preserve her physical and mental health. Throughout the process midwives play a key role in supporting women's complex psychological and clinical needs. To gain a deeper understanding of the role of midwives in TOP care after 20 weeks, including the support they might need and the impacts caring for women who are having a TOP may have on them. Eight midwives from two District Health Boards were interviewed about their experiences of caring for women having a TOP after 20 weeks. Transcripts were analysed by applying a hermeneutic-phenomenological lens. Three themes emerged: "A different kind of midwife", "Staying true to oneself" and "Melting an Iceberg". TOP care is a different role within midwifery as midwives facilitate death in the space of birth. Immersing themselves in women's emotional space they create meaningful connections to support their complex needs and provide a positive birth experience. Yet, midwives are unprepared for the emotional effects of repeatedly caring for women undergoing TOP. Lacking appropriate support they can experience increasing, lasting grief. Midwives' experiences of providing TOP care are complex, intense and have lifelong impact. Their role in the context of TOP is highly specialised and must be valued and supported.


New expectations from the well-known medicinal properties of Arctium lappa.
AMP-activated protein kinase (AMPK) serves as a major regulator of energy homeostasis and is activated by different glucose-lowering agents. Indeed, AMPK has been identified as an attractive target for the development of innovative molecules to treat type 2 diabetes. In this issue of Diabetologia (doi: 10.1007/s00125-011-2366-3 ), Huang and co-workers report that arctigenin activates muscle uptake of glucose and inhibits hepatocyte gluconeogenesis and lipogenesis by reducing mitochondrial respiration and inducing AMPK activity. Importantly, it is reported that arctigenin improves glucose and lipid metabolism in ob/ob mice. Based on this evidence, Huang and co-workers suggest that arctigenin may represent a valuable lead compound for developing innovative glucose-lowering molecules. While these findings are not entirely novel and mechanistic investigations are needed, the results strongly support the concept that arctigenin deserves to be further considered because of its several potentially beneficial in vivo effects. In particular, the authors conclude that further mechanistic studies on arctigenin might provide novel insight and opportunities for selective modulation of subcutaneous and visceral fat mass.


Pseudomonas aeruginosa hijacks the murine nitric oxide metabolic pathway to evade killing by neutrophils in the lung.
Neutrophils play a critical role in the eradication of Pseudomonas aeruginosa, a major pathogen causing lung infection. However, the mechanisms used by the pathogen to evade neutrophil-mediated killing remain poorly understood. Using a high-density transposon screen, we find that P. aeruginosa colonization in the lung is promoted by pathogen nitrite reductase nirD. nirD is required for ammonia production from nitrite, a metabolite derived from nitrogen oxide (NO) generated by inducible NO synthetase (iNOS) in phagocytes. P. aeruginosa deficient in nirD exhibit reduced survival in wild-type neutrophils but not in iNOS-deficient neutrophils. Mechanistically, nirD enhances P. aeruginosa survival in neutrophils by inhibiting the localization of the pathogen in late phagosomes. P. aeruginosa deficient in nirD show impaired lung colonization after infection in wild-type mice but not in mice with selective iNos deficiency in neutrophils. Thus, P. aeruginosa uses neutrophil iNOS-mediated NO production to limit neutrophil pathogen killing and to promote its colonization in the lung.


[Thoracic fluid content - a possible determinant of ventilatory efficiency in patients with heart failure].
Ventilatory efficiency, evaluated by cardiopulmonary exercise testing (CPET), has considerable prognostic value in patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD). Its determinants nevertheless remain controversial. To investigate the possible correlation between parameters of ventilatory efficiency obtained by CPET and thoracic fluid content (TFC), assessed by thoracic electrical bioimpedance (TEB), in patients with CHF due to LVSD. We studied 120 patients with LVSD and CHF, referred to our laboratory for CPET: 76% male, age 52.1 ± 12.1 years, 37% of ischemic etiology, left ventricular ejection fraction 27.6 ± 7.9%, 83% in sinus rhythm, 96% receiving ACEIs and/or ARBs and 79% beta-blockers, and 20% treated with a cardiac resynchronization device. TEB studies were performed after 15 minutes of rest, prior to symptom-limited treadmill CPET, using the modified Bruce protocol. CPET-derived peak oxygen consumption (pVO(2)), the slope of the relationship between minute ventilation (VE) and carbon dioxide production (VCO(2)), VE/VCO(2) at the anaerobic threshold (AT), and TFC assessed by TEB were considered for analysis. TFC ranged between 20.6 and 45.8kOhm-1, mean 32.2, SD=5.7, median 32.7, pVO(2) 8.9-40.6 ml/kg/min, mean 21.0, SD 6.2, median 20.2, VE/VCO(2) slope 19.8-60.7, mean 30.7, SD 7.9, median 29.1 and VE/VCO(2) at AT 21-62, mean 33.1, SD 7.5, median 31.5. By linear regression, TFC did not correlate with pVO(2) (r=0.05, p=0.58), but showed correlation with parameters of ventilatory efficiency: r=0.20, p=0.032, r(2)=0.04 for VE/VCO(2) slope and r=0.25, p=0.009, r(2)=0.06 for VE/VCO(2) at AT. TFC correlates with CPET parameters of ventilatory efficiency in patients with CHF due to LVSD, suggesting that it may be one of its determinants.


Is a liquid-based cytology more sensitive than a conventional Pap smear?
The comparative sensitivity of liquid-based cytology (LBC) test and conventional Papanicolaou (Pap) smears is controversial. This study analyses the distribution of cytology, histology, colposcopy and large loop excision of the transformation zone among women screened in Iceland with LBC at the Cancer Detection Clinic in Reykjavik and with a conventional Pap smear outside the Detection Clinic in 2007-2011. The study material included 42 654 LBC tests from 20 439 women and 103 909 Pap smears from 61 574 women. The period 2000-2004 is used to correct for potential bias as a result of unequal distribution of the studied parameters between the study sites before the introduction of LBC. The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears, increased detection of low-grade squamous intraepithelial lesion (LSIL)/atypical cytology and referrals to colposcopy, and an increased detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) irrespective of age. LBC increased significantly the detection rates of high-grade squamous intraepithelial lesion or worse (HSIL+) cytology and CIN3+ histology only in women under 40 years of age. Taking into consideration the unequal prevalence of the studied parameters between the study sites in 2000-2004 indicated, however, that LBC only affected the rate of inadequate and low-grade cytology tests under the age of 40 years. Positive predictive values for CIN2+ were not significantly different between the tests. The study results support the view that LBC is no more sensitive than Pap smears for the detection of HSIL+ and CIN2+ irrespective of age. LBC decreased the rate of inadequate smears, but increased the rate of low-grade cytology under the age of 40 years and decreased the total rate of abnormal smears over the age of 40 years.


Development of sensory innervation in rat tibia: co-localization of CGRP and substance P with growth-associated protein 43 (GAP-43).
The development of sensory innervation in long bones was investigated in rat tibia in fetuses on gestational days (GD) 16-21 and in neonates and juvenile individuals on postnatal days (PD) 1-28. A double immunostaining method was applied to study the co-localization of the neuronal growth marker growth-associated protein 43 (GAP-43) and the pan-neuronal marker protein gene product 9.5 (PGP 9.5) as well as that of two sensory fibre-associated neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP). The earliest, not yet chemically coded, nerve fibres were observed on GD17 in the perichondrium of the proximal epiphysis. Further development of the innervation was characterized by the successive appearance of nerve fibres in the perichondrium/periosteum of the shaft (GD19), the bone marrow cavity and intercondylar eminence (GD21), the metaphyses (PD1), the cartilage canals penetrating into the epiphyses (PD7), and finally in the secondary ossification centres (PD10) and epiphyseal bone marrow (PD14). Maturation of the fibres, manifested by their immunoreactivity for CGRP and SP, was visible on GD21 in the epiphyseal perichondrium, the periosteum of the shaft and the bone marrow, on PD1 in the intercondylar eminence and the metaphyses, on PD7 in the cartilage canals, on PD10 in the secondary ossification centres and on PD14 in the epiphyseal bone marrow. The temporal and topographic pattern of nerve fibre appearance corresponds with the development of regions characterized by active mineralization and bone remodelling, suggesting a possible involvement of the sensory innervation in these processes.


Rare Case of Dumbbell-Shaped Spinal Cavernous Hemangioma and Literature Review.
Spinal epidural cavernous hemangiomas are rare vascular malformations. Exceptionally, they present with dumbbell-shaped morphology. When they happen, it's mandatory to include their pathology in the differential diagnosis because of their similarity to schwannomas. We report the case of a 72-year-old woman with a dumbbell-shaped thoracic epidural cavernous hemangioma. A literature review of diagnostic features and current treatment options are also discussed. Surgery is safe and effective in both improving patient condition and preventing acute hemorrhage that can worsen the outcome, causing neurologic and potentially irreversible deficits. The favorable result we obtained in our patient suggests that surgery should be evaluated as the first option, even in patients with large epidural cavernous hemangiomas.


Robust design of a logistics system using FePIA procedure and analysis of trade-offs between CO2 emissions and net present value.
The problems of flexible planning of the design of logistics systems for the collection of food products such as raw milk can result in a decrease in the performance of critical indicators for their performance. This paper proposes a new efficient methodology for robustly designing a first-mile logistics system for storing and refrigerating milk as a perishable product considering decisions related to open facilities and the flow of products, including sustainability indices. The proposed approach is modeled as a bi-objective problem by considering the minimization of greenhouse gas emissions (CO2) produced by milk transportation canteens and the maximization of the system configuration's net present value (NPV). We have analyzed and determined the most robust configuration for the first time and explained the robustness-NPV and robustness-CO2 relationships. The proposed mathematical model is solved by the Epsilon constraints method, and the robustness is calculated considering an extension of the FePIA methodology for multiobjective problems. A novel contribution is a balance in the possible future values generated by the company related to its cash flows and the generation of CO2 emissions when using a motorized transport frequently used in the shipment of raw milk considering a new important aspect such as the volume of product transported and the slope of the path between the production farm and the storage cooling tanks.


Transvaginal US vs. CT in non-pregnant premenopausal women presenting to the ED: clinical impact of the second examination when both are performed.
To determine the clinical impact of the second examination when both CT and TVUS are obtained in the same ED visit for acute pelvic/lower abdominal symptoms in non-pregnant premenopausal women. 200 consecutive non-pregnant premenopausal women (mean age, 31.8 years; range, 18-49 years) who underwent both ED-based TVUS and abdominopelvic CT evaluation for acute symptoms over a 12 month period were included; 107 women had TVUS first, followed by CT; 93 women had CT first. All relevant clinical, radiologic, and pathologic findings were reviewed to establish a final diagnosis. Any additional clinical impact provided by the second imaging test was assessed by two experienced abdominal radiologists. Initial TVUS was interpreted as normal (n = 63) or mentioned incidental findings (n = 11) in 69% (74/107); subsequent CT established a non-gynecologic GI/GU etiology in 25 (34%). For 37% (34/93) of CT exams interpreted as normal, TVUS added no new information. In 32 cases (34%), TVUS further excluded ovarian torsion/adnexal pathology when initial CT was indeterminate/equivocal. Overall, CT following TVUS provided a key new or alternative diagnosis in 26% (28/107), whereas TVUS after CT provided a relevant new/alternative diagnosis in only 1/93 cases (p < 0.001). In nine cases (8%), CT confirmed a positive US diagnosis but detected relevant additional diagnostic information. CT following negative TVUS frequently identified a non-gynecologic cause of acute pelvic or lower abdominal symptoms in non-pregnant premenopausal women, whereas the main benefit of TVUS after CT was more confident exclusion of ovarian torsion.


Clinical characteristics and evolution of 71 neonates born to mothers with COVID-19 at a tertiary center in Brazil.
Limited data are available on pregnant women with COVID-19 and their neonates. This study aimed to describe clinical characteristics and evolution from birth to discharge of a retrospective cohort of 71 neonates, with one set of twins, born to women with COVID-19 diagnosed at the end of pregnancy. The authors included all newborns admitted into a neonatal unit of a tertiary hospital in Brazil, between March 2020 and March 2021, whose unvaccinated mothers had COVID-19 symptoms and RT-PCR (Real-Time Polymerase Chain Reaction) for SARS-CoV-2 positive within fourteen days prior to delivery. Newborns to mothers with COVID-19 symptoms and negative tests for SARS-CoV-2 were excluded. The main route of birth delivery was cesarean, corresponding to 60 pregnant women (84.5%). The foremost indications for cesarean were pregnant with critical disease (24.6%) and acute fetal distress (20.3%). The mean birth weight was 2452 g (865‒3870 g) and the mean gestational age was 345/7 weeks (25‒40 weeks). There were 45 premature newborns (63.3%), of which 21 newborns (29.5%) were less than 32 weeks of gestational age. RT-PCR for SARS-CoV-2 on oropharyngeal swabs was positive in 2 newborns (2.8%) and negative in the other 69 newborns (97.2%). Most newborns (51.4%) needed respiratory support. Therapeutic interventions during hospitalization were inotropic drugs (9.9%), antibiotics (22.8%), parenteral nutrition (26.8%), and phototherapy (46.5%). Maternal COVID-19 diagnosticated close to delivery has an impact on the first days of neonatal life.


BCB1, a member of the acyl-coenzyme A synthetase family, regulates the morphogenesis and pathogenicity of Botrytis cinerea.
Botrytis cinerea is a non-host-specific phytopathogenic fungus capable of infecting numerous cash crops. Here, we analyzed the functions of the Bcb1 gene in B. cinerea, which encodes a membrane protein belonging to the acyl-coenzyme A synthase family. Compared to the wild type, Bcb1-deletion mutants exhibited obvious morphological abnormalities, including slower vegetative growth and reduced melanin production. The absence of Bcb1 causes B. cinerea to form only small and incompletely developed infection cushions and fail to produce spores. The Bcb1 mutants displayed hypersensitivity to the membrane stressor SDS, the cell wall stressor Congo red, and the oxidative stressor H2O2 and increased resistance to intracellular osmotic stress caused by KCl compared to the wild-type strain. However, there were no differences in tolerance to extracellular osmotic stress caused by NaCl. The deletion of Bcb1 also caused a reduction in pathogenicity. The qRT‒PCR results showed that the genes Bcpks12 and Bcpks13, which are related to melanin biosynthesis, and Bcpg2, BcBOT2, and cutA, which are related to virulence, were downregulated in ∆Bcb1. These data suggest that BCB1 is important for conidial morphogenesis, and pathogenesis in B. cinerea.


Studies on the liver sequestration of lymphocytes bearing membrane-associated galactose-terminal glycoconjugates: reversal with agents that effectively compete for the asialoglycoprotein receptor.
The removal of "effete" glycoproteins from the circulation represents a proposed physiologic role for the hepatocyte asialoglycoprotein receptor. Our experiments support the hypothesis that this receptor may also be directly involved in the removal from the circulation of cells bearing asialoglycoconjugates. We report that the enhanced liver localization of neuraminidase-treated lymphocytes can be competitively inhibited by the coinjection of asialofetuin (ASF). Fetuin itself was without effect. Competitive inhibition of the liver receptor allowed normal localization to lymphoid tissues of the enzyme-treated lymphocytes, a condition which persisted as long as free ASF was present in the circulation. Our studies support the concept that cell surface carbohydrates play an important role in the tissue distribution of circulating lymphocytes. The process of thymocyte maturation, bone marrow transplantation, and the adoptive immunotherapy with continuous T-cell lines represent conditions where recirculation potential may be influenced by the presence of galactose terminal glycoconjugates.


Glutathione transferase isoenzymes in olfactory and respiratory epithelium of cattle.
Glutathione transferase (GST) was investigated in the olfactory and respiratory epithelium of cattle. A significantly more abundant GST in terms of either protein amount or activity was found in the olfactory rather than in the respiratory epithelium. No apparent qualitative differences in the isoelectric focusing, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and HPLC profiles were noted in the reduced glutathione (GSH) affinity purified GST pool of olfactory and respiratory epithelium. Both tissues have at least six GST isoenzymes with isoelectric point values of 4.9 (peak I), 5.3 (peak II), 5.95 (peak III), 6.5 (peak IV), 7.1 (peak V) and 9.3 (peak VI). From both tissues at least seven different GST subunits can be resolved by HPLC analysis. The GST isoenzymes having pI at 5.3 and 9.3 were predominantly expressed in the olfactory than in the respiratory epithelium. These latter forms conjugate GSH efficiently with alkenals and hydroperoxides, respectively. Kinetic, immunological and structural properties, including HPLC analysis and N-terminal region amino acid sequence seem to indicate that the bovine nasal mucosa tissue in addition to a GST subunit which is orthologue to rat subunit 8 (alpha class) express tissues specific subunits.


The relation between dietary zinc and immune status in saudi adults.
Although there is an increased interest in zinc intake and its role in boosting immunity, to our knowledge, no studies have investigated the relationship between dietary zinc intake and immunity in Saudi adults. This cross-sectional study aimed to measure the extent to which the dietary zinc impacted the immune health of 252 Saudi adults aged 18 years and above. Immune health was assessed using the Immune Status Questionnaire (ISQ), and dietary zinc intake was estimated using an adapted zinc-specific version of the Saudi Food Frequency Questionnaire (SFFQ). Three scores were calculated for use in the statistical analyses (zinc intake score, immune status score, and health status score). A linear regression analysis was used to investigate the association between the dietary zinc intake and immune and health status scores. The means of dietary zinc intake, ISQ, and health status scores were 46.94, 7.10, and 7.84, respectively. We found that a high zinc intake score was directly associated with immune status score (p = 0.006) but was not associated with the health status score. The association remained significant after controlling for socio-demographic factors. Further studies are needed to confirm these findings.


[Region of the prune locus in Drosophila melanogaster is transcriptionally saturated].
Using Northern analysis three transcription areas are detected in the gene prune region from which three different mRNAs 1.8, 1.75 and 1.0 kb in length transcribe. Corresponded cDNAs are cloned. Only 1.8 kb mRNA is shown to be changed in size and quantity in the case of the pn1 and pn3 mutations. This mRNA seems to be a gene prune transcript. From the analysis of the portion of cDNA c1.1 nucleotide sequence corresponded 1.75 kb mRNA follows that its putative amino acid product contains a heme-binding site which is characterized for P450 cytochrome superfamily. On the basis of presented results and published data by Teng et al [1] it may be concluded that at least five different mRNAs transcribe in the gene prune region in area spanning about 10 kb.


Butanol-isopropanol fermentation with oxygen-tolerant Clostridium beijerinckii XH29.
Acetone-butanol-ethanol (ABE) fermentation is a traditional way for solvents production through bioconversion by Clostridium species. It is still a challenge to obtain metabolic engineering strains with high ABE yield. Screening strains with remarkable characteristics from nature and improving ABE yield by mutation are viable approaches. Clostridium beijerinckii XH 0906, a newly isolated strain, produces butanol and isopropanol (BI) as the main end-products (9.1 g/L BI) during fermentation with glucose as the sole carbon source. The screening process for this strain was performed under aerobic conditions rather than anaerobic environment. Thus, it is a robust stain capable of oxygen-tolerant BI fermentation. Furthermore, C. beijerinckii XH 0906 fermented xylose and glucose simultaneously to produce BI. A mutant strain obtained by ultraviolet (UV) mutagenesis, C. beijerinckii XH 29, had improved BI production capacity and could produce 17.0 g/L BI and 18.4 g/L BI using glucose or corn stover hydrolysate, respectively as the carbon source. Interestingly, C. beijerinckii XH 29 also produced up to 19.3 g/L isopropanol through fermentation of a glucose-acetone mix. These results indicate that C. beijerinckii XH 29 is an excellent BI producer with great potential for industrial applications.


Tripartite motif family proteins in inflammatory bowel disease: Mechanisms and potential for interventions.
Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease that poses a heavy burden to the global healthcare system. However, the current paucity of mechanistic understanding of IBD pathogenesis hampers the development of aetiology-directed therapies. Novel therapeutic options based on IBD pathogenesis are urgently needed for attaining better long-term prognosis for IBD patients. The tripartite motif (TRIM) family is a large protein family including more than 70 structurally conservative members, typically characterized by their RBCC structure, which primarily function as E3 ubiquitin ligases in post-translational modification. They have emerged as regulators of a broad range of cellular mechanisms, including proliferation, differentiation, transcription and immune regulation. TRIM family proteins are involved in multiple diseases, such as viral infection, cancer and autoimmune disorders, including inflammatory bowel disease. This review provides a comprehensive perspective on TRIM proteins' involvement in the pathophysiology and progression of IBD, in particular, on intestinal mucosal barriers, gene susceptibility and opportunistic infections, thus providing novel therapeutic targets for this complicated disease. However, the exact mechanisms of TRIM proteins in IBD pathogenesis and IBD-related carcinogenesis are still unknown, and more studies are warranted to explore potential therapeutic targets of TRIM proteins in IBD.


Long-term costs and outcomes in psoriatic arthritis patients not responding to conventional therapy treated with tumour necrosis factor inhibitors: the extension of the Psoriatic Arthritis Cost Evaluation (PACE) study.
Poor information on long-term outcomes and costs on tumour necrosis factor (TNF) inhibitors in psoriatic arthritis (PsA) are available. Our aim was to evaluate long-term costs and benefits of TNF- inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs). Fifty-five out of 107 enrolled patients included in the study at one year, completed the 5-year follow-up period. These patients were enrolled in 8 of 9 centres included in the study at one year. Patients aged older than 18 years, with different forms of PsA and failure or intolerance to tDMARDs therapy were treated with anti-TNF agents. Information on resource use, health-related quality of life (HRQoL), disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before TNF inhibitor therapy and after 1 and 5 years were compared. The majority of patients (46 out of 55; 83.6%) had a predominant or exclusive peripheral arthritis and 16.4% had predominant or exclusive axial involvement. There was a statistically significant improvement of the most important clinical variables after 1 year of follow-up. These improvements were maintained also after 5 years. The direct costs increased by approximately €800 per patient-month after 1 year, the indirect costs decreased by €100 and the overall costs increased by more than €700 per patient-month due to the cost of TNF inhibitor therapy. Costs at 5 year were similar to the costs at 1 year. The HRQoL parameters showed the same trends of the clinical variables. EQ-5D VAS, EQ-5D utility and SF-36 PCS score showed a significant improvement after 1 year, maintained at 5 years. SF-36 MCS showed an improvement only at 5 years. The results of our study suggest that TNF blockers have long-term efficacy. The higher cost of TNF inhibitor therapy was balanced by a significant improvement of HRQoL, stable at 5 years of follow-up. Our results need to be confirmed in larger samples of patients.


Basic experiments on oral administration of 5-fluorouracil emulsion as adjuvant chemotherapy to surgical treatment for gastric cancer.
Oral administration of 5-fluorouracil (5-FU) emulsion was compared experimentally with that of 5-FU aqueous solution as to the degree of absorption and tissue distribution. After oral administration of both the 5-FU emulsion and the 5-FU solution, 5-FU was detected at the highest level in both the stomach and the duodenum. This seems to suggest that 5-FU is strongly affinitive to the tissues of the gastrointestinal tract. As to the relative concentration of these two forms of the drug, the oral administration of the 5-FU emulsion resulted in a maximum value 1.5 times higher than that of the 5-FU solution. An appreciable concentration of 5-FU was maintained for a considerably long time with the administration of 5-FU emulsion. In the lymph, the maximum level of the 5-FU emulsion was three times higher than that of the 5-FU solution. The drug concentration of the 5-FU emulsion remained higher than that of the 5-FU solution through the entire duration of the experiment. Regarding the drug concentration in the regional lymph nodes, the pattern demonstrated was almost the same as in the lymph itself. It is expected that the oral administration of 5-FU emulsion may be useful as an adjuvant to the surgical treatment of gastric cancer, because of the high drug concentration resulting both in the gastrointestinal tract and in the regional lymph nodes.


A clinical perspective on the analysis and presentation of the number of incontinence episodes following treatment for OAB.
To provide a clinical view and interpretation on the methods for analysis of incontinence in patients with overactive bladder. Results are analyzed using the total number of incontinence episodes in a 3-day diary period, using fixed and random effect Poisson regression models to calculate ratio of event rates and 95% confidence interval (CI) together with P-values and are compared with the analysis of the mean number of incontinence episodes/24 hr using analysis of covariance models to calculate P-values and 95% CI for the difference between treatments. Using random effects Poisson regression models demonstrated that the number of incontinence episodes was reduced by 26% more with mirabegron 50 mg than with placebo. For solifenacin 5 and 10 mg, treatment resulted in a 43% (41%) greater decrease in the number of incontinence episodes compared with placebo. Instead of providing a fixed number of incontinence episodes/24 hr that reflects the mean effect, the estimate using Poisson methodology provides an efficacy estimate that can be interpreted in the context of, and relative to, the patient's baseline (severity). Using the total number of incontinence episodes in the diary period, and expressing this as percent decrease in the number of episodes, may be easier to interpret; for example, because this results in a relative measure of effect that provides an alternative understanding of a patient's improvement at end of treatment compared with the comparator arm. Also, it is based on statistical methods that are more suitable for the analysis of count data. Neurourol. Urodynam. 35:728-732, 2016. © 2015 Wiley Periodicals, Inc.


Contrast-enhanced voiding urosonography: in vitro evaluation of a second-generation ultrasound contrast agent for in vivo optimization.
Pediatric contrast-enhanced ultrasound (CEUS) is primarily performed outside the United States where a track record for safety in intravenous and intravesical applications has been established. Contrast-enhanced voiding urosonography (ceVUS) has also been shown to have a much higher rate of vesicoureteral reflux detection compared to voiding cystourethrography. US contrast agents available in the United States differ from those abroad. Optison® (GE Healthcare, Princeton, NJ) is such an US contrast agent. While Optison® has similar characteristics to other second-generation agents, it has never been used for ceVUS. In vitro optimization of dose and imaging parameters as well as assessment of contrast visualization when delivered in conditions similar to ceVUS are necessary starting points prior to in vivo applications. To optimize the intravesical use of Optison® in vitro for ceVUS before its use in pediatric studies. The experimental design simulated intravesical use. Using 9- and 12-MHz linear transducers, we scanned 20-mL syringes varying mechanical index, US contrast agent concentration (0.25%, 0.5%, 1.0%), solvent (saline, urine, radiographic contrast agent) and time out of refrigeration. We evaluated mechanical index settings and contrast duration, optimized the contrast dose, measured the effect of urine and radiographic contrast agent, and the impact of length of time of contrast outside of the refrigerator on US contrast appearance. We scanned 50-ml saline bags to assess the appearance and duration of US contrast with different delivery systems (injection vs. infusion). Consistent contrast visualization was achieved at a mechanical index of 0.06-0.17 and 0.11-0.48 for the L9 and L12 MHz transducers (P < 0.01), respectively. Thus, it was necessary to increase the mechanical index for better contrast visualization of the microbubbles with a higher transducer frequency. The lowest mechanical index for earliest visible microbubble destruction was 0.21 for the 9 MHz and 0.39 for the 12 MHz (P < 0.01) transducers. The 0.5% US contrast agent volume to bladder filling was the most optimal. At this concentration, the mean time to visualize homogenous contrast was 2 min and destruction of approximately half of the microbubbles in the field of view occurred in 7.8 min using the 9-MHz transducer. During contrast infusion, the contrast dose needed to be reduced to 0.12% for maintenance of optimal visualization of microbubbles. There was no deleterious effect on the visualization of contrast in the presence of urine or radiographic contrast agent. Infusion of the US contrast agent speeded visualization of homogeneous enhancement compared with injection. Time outside refrigeration did not affect contrast performance. Transducer mechanical index settings need to be optimized. A very low dose of the US contrast agent Optison® will suffice for intravesical application, i.e. 0.12% to 0.50% of the bladder filling volume. The presence of urine or radiographic contrast agent did not compromise contrast visualization. The best mode of administration is the infusion method due to fast homogenous distribution at the lowest dose of 0.12%. Leaving the US contrast agent outside the refrigerator for an hour does not affect the microbubbles.


Sepsis induces non-classic innate immune memory in granulocytes.
Secondary infection in patients with sepsis triggers a new wave of inflammatory response, which aggravates organ injury and increases mortality. Trained immunity boosts a potent and nonspecific response to the secondary challenge and has been considered beneficial for the host. Here, using a murine model of polymicrobial infection, we find that the primary infection reprograms granulocytes to boost enhanced inflammatory responses to the secondary infection, including the excessive production of inflammatory cytokines, respiratory burst, and augmented phagocytosis capacity. However, these reprogramed granulocytes exhibit "non-classic" characteristics of innate immune memory. Two mechanisms are independently involved in the innate immune memory of granulocytes: a metabolic shift in favor of glycolysis and fatty acid synthesis and chromatin remodeling leading to the transcriptional inactivity of genes encoding inhibitors of TLR4-initiated signaling pathways. Counteracting the deleterious effects of stressed granulocytes on anti-infection immunity might provide a strategy to fight secondary infections during sepsis.


Photochemical degradation of solid-state nisoldipine monitored by HPLC.
The photochemical degradation of solid-state nisoldipine, 1,4-dihydropyridine calcium antagonist, was investigated under daylight and UV light conditions. Degradation products were identified by using the retention times of corresponding standards and quantified by high-performance liquid chromatographic method. The daylight illumination induced appearance of nitrosophenylpyridine, while formation of second degradation product, nitrophenylpyridine, was observed only upon UV light illumination. The photodegradation kinetics of solid-state nisoldipine under daylight and UV light illumination belongs to class of zero-order reactions. The rate constants of disappearance of nisoldipine upon illumination were determined for raw material as well as pharmaceuticals (tablets, film-tablets and capsules).


Data Science and Precision Oncology Nursing: Creating an Analytic Ecosystem to Support Personalized Supportive Care across the Trajectory of Illness.
The authors' objective is to present an overarching framework of an analytic ecosystem using diverse data domains and data science approaches that can be used and implemented across the cancer continuum. Analytic ecosystems can improve quality practices and offer enhanced anticipatory guidance in the era of precision oncology nursing. Published scientific articles supporting the development of a novel framework with a case exemplar to provide applied examples of current barriers in data integration and use. The combination of diverse data sets and data science analytic approaches has the potential to extend precision oncology nursing research and practice. Integration of this framework can be implemented within a learning health system where models can update as new data become available across the continuum of the cancer care trajectory. To date, data science approaches have been underused in extending personalized toxicity assessments, precision supportive care, and enhancing end-of-life care practices. Nurses and nurse scientists have a unique role in the convergence of data science applications to support precision oncology across the trajectory of illness. Nurses also have specific expertise in supportive care needs that have been dramatically underrepresented in existing data science approaches thus far. They also have a role in centering the patient and family perspectives and needs as these frameworks and analytic capabilities evolve.


Unusual Lesion Caused by Food Displacement Into the Oral Mucosa, Mimicking a Sinus Tract.
This article reports an unusual case of foreign body lesion on the oral mucosa. A 61-year-old man, with no previous traumatic episode, presented with a small swelling resembling a sinus tract on the mucosa in the anterior mandible, adjacent to the left central and lateral incisors. Because of a discrete drainage of serous/purulent exudate, the clinician initially suspected endodontic involvement; however, the adjacent teeth were caries-free, responded positively to pulp tests, and the periapical tissues were radiographically normal. Exploration of the lesion opening under an operating microscope revealed a small seed associated with a dark filamentous structure; both were removed and processed for histologic examination. The seed was from a fig, and was germinating under the mucosa conditions. Bacterial colonization of the vegetable structures and polymorphonuclear leukocyte accumulations were histologically observed. The mucosa healed completely and uneventfully over the following weeks.


Interrogating the architecture of protein assemblies and protein interaction networks by cross-linking mass spectrometry.
Proteins are involved in almost all processes of the living cell. They are organized through extensive networks of interaction, by tightly bound macromolecular assemblies or more transiently via signaling nodes. Therefore, revealing the architecture of protein complexes and protein interaction networks is crucial to understand their function. Towards this aim, cross-linking mass spectrometry (XL-MS), which allows the elucidation of structures and interactions of proteins at low-resolution, has emerged as a valuable technology. Especially in recent years, the substantial development of cross-linking approaches and MS-based technologies, has led to noteworthy advances in the analysis of purified/in vitro reconstituted very large (megaDa) protein assemblies and various endogenous protein complexes in cells. Here we review the advances of XL-MS technologies and highlight some of the most recent studies. They clearly indicate that current XL-MS methodologies are ideally positioned to bridge the gap between proteomic-based interactome studies and high-resolution structural biology-based technologies.


Fold change and p-value cutoffs significantly alter microarray interpretations.
As context is important to gene expression, so is the preprocessing of microarray to transcriptomics. Microarray data suffers from several normalization and significance problems. Arbitrary fold change (FC) cut-offs of >2 and significance p-values of <0.02 lead data collection to look only at genes which vary wildly amongst other genes. Therefore, questions arise as to whether the biology or the statistical cutoff are more important within the interpretation. In this paper, we reanalyzed a zebrafish (D. rerio) microarray data set using GeneSpring and different differential gene expression cut-offs and found the data interpretation was drastically different. Furthermore, despite the advances in microarray technology, the array captures a large portion of genes known but yet still leaving large voids in the number of genes assayed, such as leptin a pleiotropic hormone directly related to hypoxia-induced angiogenesis. The data strongly suggests that the number of differentially expressed genes is more up-regulated than down-regulated, with many genes indicating conserved signalling to previously known functions. Recapitulated data from Marques et al. (2008) was similar but surprisingly different with some genes showing unexpected signalling which may be a product of tissue (heart) or that the intended response was transient. Our analyses suggest that based on the chosen statistical or fold change cut-off; microarray analysis can provide essentially more than one answer, implying data interpretation as more of an art than a science, with follow up gene expression studies a must. Furthermore, gene chip annotation and development needs to maintain pace with not only new genomes being sequenced but also novel genes that are crucial to the overall gene chips interpretation.


Firing properties of cat basal forebrain neurones during sleep-wakefulness cycle.
Neuronal activity was studied in the basal forebrain area (BFA) of freely moving cats during wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS). Two classically synchronizing and hypnogenic regions, the preoptic area (POA) and the olfactory tubercle (OT) were explored by microelectrodes. Compared to W, the discharge rate in most of the POA cells was not modified or was slightly reduced by SWS, but it was increased by PS. Half of the OT cells increased slightly their firing frequency during falling asleep. A great proportion of OT neurones showed facilitation of activity during PS also, which in half of the cells started already in the last seconds of SWS. The results are discussed from the point of view of the synchronizing and hypnogenic influence attributed to POA and OT.


Insects breeding in pig carrion in two environments of a rural area of the state of minas gerais, Brazil.
The main objective of this study was to identify potential forensic indicators in the insect fauna associated with pig carrion and the pattern of insect succession during the decomposition process in two environments of a rural area in Uberlândia, State of Minas Gerais, Brazil. The study was conducted at two locations: in a pasture and in a fragment of a semi-deciduous forest (vegetation profile of the Cerrado biome) in two different seasons (rainy and dry) of 2010. The decomposition process was more rapid in the rainy season. More than 32,000 insects belonging to 17 species of 6 families of Diptera and 2 species of Coleoptera bred in the carcasses. The majority of Diptera bred in the first three stages of decomposition. However, Phoridae and Coleoptera bred mainly in the last two stages. The insects bred more abundantly in the pasture and in the humid season. The exceptions were the Fanniidae (Diptera), which bred more abundantly in the forest and the Dermestidae and Cleridae (Coleoptera), which did not demonstrate any preference in terms of environments and were more abundant in the dry season, respectively. Species such as Chrysomya albiceps (Wiedemann), Peckia (Patonella) intermutans (Walker), Necrobia rufipes (De Geer), and Dermestes maculatus (De Geer) may be potential indicators of post-mortem interval. Hemilucilia segmentaria (Fabricius) and Ophyra aenescens (Wiedemann) may be indicators of localization of the natural environment, while Musca domestica Linnaeus may be an indicator of the anthropic environment. The study thus presented many species of potential forensic indicators in rural areas of this region.


Use of genetic programming, logistic regression, and artificial neural nets to predict readmission after coronary artery bypass surgery.
As many as 14 % of patients undergoing coronary artery bypass surgery are readmitted within 30 days. Readmission is usually the result of morbidity and may lead to death. The purpose of this study is to develop and compare statistical and genetic programming models to predict readmission. Patients were divided into separate Construction and Validation populations. Using 88 variables, logistic regression, genetic programs, and artificial neural nets were used to develop predictive models. Models were first constructed and tested on the Construction populations, then validated on the Validation population. Areas under the receiver operator characteristic curves (AU ROC) were used to compare the models. Two hundred and two patients (7.6 %) in the 2,644 patient Construction group and 216 (8.0 %) of the 2,711 patient Validation group were re-admitted within 30 days of CABG surgery. Logistic regression predicted readmission with AU ROC = .675 ± .021 in the Construction group. Genetic programs significantly improved the accuracy, AU ROC = .767 ± .001, p < .001). Artificial neural nets were less accurate with AU ROC = 0.597 ± .001 in the Construction group. Predictive accuracy of all three techniques fell in the Validation group. However, the accuracy of genetic programming (AU ROC = .654 ± .001) was still trivially but statistically non-significantly better than that of the logistic regression (AU ROC = .644 ± .020, p = .61). Genetic programming and logistic regression provide alternative methods to predict readmission that are similarly accurate.


Zolpidem use and hip fractures in older people.
The widespread use of sedative-hypnotics in older populations makes it imperative to identify hazardous regimens that should be avoided and safer regimens that may be used preferentially by older people. Although benzodiazepines have been shown to increase fall and fracture risk, zolpidem, a nonbenzodiazepine hypnotic, has been advocated as a safer alternative. Case-control study of hip fracture cases and controls in 1994. All subjects were age 65 and older and enrolled in Medicare, and in Medicaid or the Pharmaceutical Assistance to the Aged and Disabled program of New Jersey. Cases (n=1,222) were patients who underwent surgical repair of a hip fracture. They were frequency-matched to four controls (n=4,888) based on age and gender. Use of sedative-hypnotics and other medications was assessed in the 180 days before the index event. We assessed other covariates, including demographic, clinical, and healthcare utilization variables in the prior 180 days. Zolpidem use was associated with a significant increased risk of hip fracture (adjusted odds ratio (AOR) 1.95; 95% confidence interval (CI)=1.09-3.51). Other psychotropic medication classes with significantly increased risks included benzodiazepines (AOR 1.46; 95% CI=1.21-1.76), antipsychotic medications (AOR 1.61; 95% CI=1.29-2.01), and antidepressants (AOR 1.46; 95% CI=1.22-1.75). In subanalyses, preferential use of zolpidem by subjects at greater risk of hip fracture did not appear to explain the apparent risk of hip fracture with zolpidem use. Use of zolpidem by older people was associated with nearly twice the risk of hip fracture, even after controlling for possible demographic and clinical confounders. Rather than being a safer alternative, zolpidem may be associated with risks that are as great as those seen with conventional benzodiazepines in older patients.


Bioartificial liver with reprogrammed hepatocytes ready for prime time.
In this issue, Wang et al.1 provide evidence of the pre-clinical as well as the clinical utility of in vitro-generated directly reprogrammed human hepatocytes in bioartificial liver. This approach will help offer patients a more curative surgical therapy for liver cancer and improve survival rates.


The interactions between chromatic aberration, defocus and stimulus chromaticity: implications for visual physiology and colorimetry.
It has long been recognised that chromatic aberration can introduce luminance artifacts into nominally isoluminant colour stimuli. In this study the effects of chromatic aberration (along with those of defocus and stimulus spatial frequency) on the chromaticity of the retinal image are considered. Such optical effects have important methodological and functional implications for visual physiology. The "Silent Substitution" principle is a fundamental feature of modern colorimetry, being employed in both psychophysical and electrophysiological approaches to the visual system. The theoretical colour spaces introduced by MacLeod and Boynton (1979) and Derrington et al. (1984) are also ultimately based on this principle. All such applications of the silent substitution principle are sensitive to the optical effects of chromatic aberration, defocus, spatial frequency and stimulus chromaticity. The spatial acuity of the mechanisms of colour vision are appreciably lower than those of the luminance system (Mullen, 1985). In addition chromatic aberration has been shown to be a cue to ocular accommodation (Fincham, 1951). The analysis presented in this study suggests a possible explanation for these findings in terms of the ecological and computational constraints placed on the visual system by chromatic aberration.


Integrative analysis of scRNA-seq and GWAS data pinpoints periportal hepatocytes as the relevant liver cell types for blood lipids.
Liver, a heterogeneous tissue consisting of various cell types, is known to be relevant for blood lipid traits. By integrating summary statistics from genome-wide association studies (GWAS) of lipid traits and single-cell transcriptome data of the liver, we sought to identify specific cell types in the liver that were most relevant for blood lipid levels. We conducted differential expression analyses for 40 cell types from human and mouse livers in order to construct the cell-type specifically expressed gene sets, which we refer to as construction of the liver cell-type specifically expressed gene sets (CT-SEGS). Under the assumption that CT-SEGS represented specific functions of each cell type, we applied stratified linkage disequilibrium score regression to determine cell types that were most relevant for complex traits and diseases. We first confirmed the validity of this method (of delineating functionally relevant cell types) by identifying the immune cell types as relevant for autoimmune diseases. We further showed that lipid GWAS signals were enriched in the human and mouse periportal hepatocytes. Our results provide important information to facilitate future cellular studies of the metabolic mechanism affecting blood lipid levels.


Optimized intermolecular potential for nitriles based on Anisotropic United Atoms model.
An extension of the anisotropic united atoms intermolecular potential model is proposed for nitriles. The electrostatic part of the intermolecular potential is calculated using atomic charges obtained by a simple Mulliken population analysis. The repulsion-dispersion interaction parameters for methyl and methylene groups are taken from transferable AUA4 literature parameters [Ungerer et al., J. Chem. Phys., 2000, 112, 5499]. Non-bonding Lennard-Jones intermolecular potential parameters are regressed for the carbon and nitrogen atoms of the nitrile group (-C[triple bound] N) from experimental vapor-liquid equilibrium data of acetonitrile. Gibbs Ensemble Monte Carlo simulations and experimental data agreement is very good for acetonitrile, and better than previous molecular potential proposed by Hloucha et al. [J. Chem. Phys., 2000, 113, 5401]. The transferability of the resulting potential is then successfully tested, without any further readjustment, to predict vapor-liquid phase equilibrium of propionitrile and n-butyronitrile.


Transcriptome coexpression analysis using ATTED-II for integrated transcriptomic/metabolomic analysis.
Transcriptome coexpression analysis is an excellent tool for predicting the physiological functions of genes. It is based on the "guilt-by-association" principle. Generally, genes involved in certain metabolic processes are coordinately regulated. In other words, coexpressed genes tend to be involved in common or closely related biological processes. Genes of which the metabolic functions have been identified are preselected as "guide" genes and are used to check the transcriptome coexpression fidelity to the pathway and to determine the threshold value of correlation coefficients to be used for subsequent analysis. The coexpression analysis provides a network of the relationships between "guide" and candidate genes that serves to create the criteria by which gene functions can be predicted. Here we describe a procedure to narrow down the number of candidate genes by means of the publicly available database, designated Arabidopsis thaliana trans-factor and cis-element prediction database (ATTED-II).


Usefulness of the Japan narrow-band imaging expert team classification system for the diagnosis of sessile serrated lesion with dysplasia/carcinoma.
Sessile serrated lesion (SSL) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSL can be difficult to diagnose with conventional endoscopy, because most SSLs with dysplasia/carcinoma have subtle mucosal features. Many studies have indicated that narrow-band imaging (NBI) observations of colorectal polyps are very useful, accurate predictors of histology. We aimed to verify the usefulness of the Japan NBI Expert Team (JNET) classification system for the diagnosis of SSLs with dysplasia/carcinoma. We examined 709 endoscopically or surgically resected lesions that were pathologically diagnosed as SSL, including 647 with no dysplasia, 37 with low-grade dysplasia, 15 with high-grade dysplasia, and 10 with submucosal invasive carcinoma. We retrospectively evaluated their clinicopathologic characteristics and conventional endoscopic and magnifying NBI endoscopic findings using the JNET system. Cases in all groups were more frequently located in the proximal colon. Submucosal invasive carcinomas were significantly larger than no dysplasia and low-grade dysplasia lesions. Almost all studied lesions (96.3%) were covered with a mucus cap. Five hundred and eighty (81.8%) lesions exhibited dark spots inside the crypts, which are NBI findings' characteristic of SSL. As for the JNET classification of magnifying NBI endoscopic findings, all 709 lesions showed Type 1. Six hundred and eighteen (95.5%) SSLs with no dysplasia lesions exhibited Type 1 only, whereas 52 (83.9%) SSLs with dysplasia/carcinoma had a combination of Type 1 and Type 2A, 2B, or 3, corresponding to SSL and dysplasia/carcinoma, respectively. The JNET classification had high sensitivity (83.9%), specificity (95.5%), and overall diagnostic accuracy (94.5%) for diagnosing SSLs with dysplasia/carcinoma. Use of magnifying NBI endoscopy with the JNET classification might be useful for diagnosing SSLs with dysplasia/carcinoma. This increased awareness may also improve the recognition of SSLs with dysplasia/carcinoma.


Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations.
Here we summarized what is known at the present about function, structure and effect of mutations in the human prolidase. Among the peptidases, prolidase is the only metalloenzyme that cleaves the iminodipeptides containing a proline or hydroxyproline residue at the C-terminal end. It is relevant in the latest stage of protein catabolism, particularly of those molecules rich in imino acids such as collagens, thus being involved in matrix remodelling. Beside its intracellular functions, prolidase has an antitoxic effect against some organophosphorus molecules, can be used in dietary industry as bitterness reducing agent and recently has been used as target enzyme for specific melanoma prodrug activation. Recombinant human prolidase was produced in prokaryotic and eukaryotic hosts with biochemical properties similar to the endogenous enzyme and represents a valid tool both to better understand the structure and biological function of the enzyme and to develop an enzyme replacement therapy for the prolidase deficiency (PD). Prolidase deficiency is a rare recessive disorder caused by mutations in the prolidase gene and characterized by severe skin lesions. Single amino acid substitutions, exon splicing, deletions and a duplication were described as causative for the disease and are mainly located at highly conserved amino acids in the sequence of prolidase from different species. The pathophysiology of PD is still poorly understood; we offer here a review of the molecular mechanisms so far hypothesized.


Disturbances in glomerular basement membrane glycosaminoglycans in experimental diabetes.
Glycosaminoglycans (GAGs) were purified from basement membranes isolated from glomeruli of control and streptozocin-induced diabetic rats and were quantitatively analyzed with a recently described competitive binding assay that is specific for and sensitive to microgram amounts of chondroitin and heparan sulfate. Total GAG content in glomeruli from diabetic rats and in the basement membranes prepared from these samples (17.22 +/- 1.45 and 6.56 +/- 0.49 micrograms/10(5) glomeruli, respectively was significantly less than that found in comparable control preparations (43.71 +/- 3.35 and 16.05 +/- 1.41 micrograms/10(5) glomeruli, respectively). The portion of total GAG in the water-soluble fraction recovered after osmotic lysis of isolated glomeruli was also markedly decreased in diabetic samples (26.11 +/- 4.55 vs. 3.30 +/- 0.32 micrograms/10(5) glomeruli, control vs. diabetic). Treatment of lysed glomeruli with the ionic detergent deoxycholate, required for liberation of the extracellular matrix from plasma membrane lipoproteins and purification of the insoluble glomerular basement membrane (GBM), resulted in solubilization of approximately 10% of the water-insoluble GAG in control samples but greater than 50% in diabetic membranes. Heparan sulfate comprised greater than 90% of the GAGs in both control and diabetic GBM, defined as the water- and detergent-insoluble matrix. The findings clearly demonstrate that the GAG content of GBM is diminished in experimental diabetes and provide evidence that the reduction in GBM anionic sites associated with diabetes derives from a decrease in the constituent GAGs of this extracellular matrix. The results further suggest that the interaction between GBM and populations of GAG associated with the surface of plasma membranes of adjacent cells is disturbed in diabetes.


Cohesion and adherence in exercise groups of patients with chronic heart diseases - a prospective study.
Objective: In cardiac rehabilitation, long-term adherence to exercise prescription is an important prerequisite to reduce mortality and the risk of recurrent cardiac events. Cohesion seems to be an important predictor of adherence when exercise is conducted in prevention settings, but in clinical settings, this relationship is currently unknown. To address this gap, the goal of this study was to determine the relationship between group cohesion and adherence in cardiac rehabilitation programs considering the duration of membership as a moderator.Design: The study was conducted with 474 participants (21.7% women), in three rehabilitation centres in North Rhine Westphalia, Germany, assessing cohesion, adherence and group membership in outpatient cardiac exercise groups.Main Outcome Measures: Cohesion was assessed using the KIT-FG and adherence was operationalized as the total number of sessions attended over a 7-week period.Results: Moderated hierarchical stepwise regression analyses revealed that perceptions of the social dimension of group cohesion significantly predicted adherence behaviour only for members with a rather long duration of membership.Conclusion: Our findings suggest that cohesion might have a differential effect on an individual's decision to regularly participate in exercise, depending on the duration of membership in the group.


Long-term albumin administration in patients with cirrhosis and ascites: A meta-analysis of randomized controlled trials.
Ascites is a common complication of cirrhosis, and it is associated with increased mortality. The aim of this study was to evaluate the efficacy of long-term albumin administration in decreasing mortality and other complications of patients with cirrhosis and ascites. A systematic review was performed using MEDLINE and Embase databases. Randomized controlled trials evaluating long-term albumin administration in patients with cirrhosis and ascites were considered eligible, as long as at least one of the following outcomes was evaluated: mortality, recurrence of ascites/need for paracentesis, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. Meta-analysis was performed using the random-effects model, through the Mantel-Haenszel method. The study protocol was registered at PROSPERO platform (CRD42019130078). The literature search yielded 1517 references. Five randomized controlled trials fulfilled the selection criteria and were included in this meta-analysis, involving 716 individuals. Patients receiving long-term albumin had significantly lower risk of recurrence of ascites/need for paracentesis when compared with controls (risk ratio = 0.56, 95% confidence interval = 0.48-0.67, P < 0.00001). There was no evidence of significant difference between the long-term albumin and control groups regarding mortality, refractory ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, gastrointestinal bleeding, or adverse events. Long-term albumin administration in patients with cirrhosis and ascites decreases recurrence of ascites/need for paracentesis. At this point, there is no evidence of significant benefits of long-term albumin administration regarding mortality or other complications of cirrhosis.


Age and domestic migration effects on workers' commuting distance.
Do older workers, including those that work beyond age 65, have different commuting patterns than their younger counterparts? With a focus on older working adults, including those that continue to work beyond age 65, this paper examines the relationship between migration, residential location, and commute distance within Toronto's commuter shed. The study utilizes data from the master file of the 2016 Canadian Census, allowing migrants to be disaggregated by duration of residence. Results indicate that living in rural areas and being a recent migrant are significantly associated with longer commutes. Furthermore, findings demonstrate that the commute distance of very recent migrants (those who migrated in the year immediately prior to the census) and individuals who moved to rural areas have the longest commute distances. As residential duration increases, commute distance decreases. Older workers have similar commuting behaviors as younger workers, although older workers who recently migrated have some of the longest commute distances as well. The online version contains supplementary material available at 10.1007/s11116-022-10341-5.


Fluoride increases rat osteoblast function and population after in vivo administration but not after in vitro exposure.
The effects of fluoride on bone tissue are now well documented by in vivo histological studies performed on both human and animal bone biopsies and demonstrating an increase in osteoblast (OB) population. In order to elucidate whether the mechanism of action of fluoride on osteoblasts was direct or indirect, 14 three-week-old Sprague-Dawley rats were selected. Seven animals received 100 ppm fluoride as sodium fluoride (NaF) in drinking water for one month. The other animals, which did not receive fluoride, were considered as controls. At the end of the experiment, femurs and vertebrae were excised and osteoblastic cells were obtained after collagenase digestion separately from each animal. The osteoblastic cells derived from control and NaF-treated rats were exposed in vitro to 10(-5) M NaF. Alkaline phosphatase (AP) activity was measured, and the cellular proliferation was assessed by 3H-thymidine incorporation. Thymidine incorporation and AP activity were significantly higher in osteoblastic cells derived from NaF-treated rats than in cells obtained from control rats (p = 0.05 and p < 0.01, respectively). In contrast, the osteoblast proliferation and activity were not modified after in vitro exposure to NaF in cells derived from control and NaF-treated rats. In conclusion, the function of osteoblasts was not modified after in vitro exposure to fluoride. In contrast, given in vivo to rats for one month, fluoride has a mitogenic effect on osteoblasts and stimulates their activity. These data emphasize the hypothesis that fluoride may act either on osteoprogenitor cells or through an indirect mechanism mediated by a cofactor.


Motor impairment in children with anxiety disorders.
This study examined the frequency and degree of motor impairment in referred children with anxiety disorders (AnxDs), compared with children with attention deficit/hyperactivity disorder (ADHD), children with comorbid AnxDs and ADHD, and nonreferred controls. All participants (n=141; 90 males, 51 females; mean age: 10 years, 1 month; range: 7-13 years) had an IQ greater than 70. Diagnoses of mental disorders were established using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (Kiddie-SADS). Motor ability was assessed using the Movement Assessment Battery for Children (M-ABC). We found that children with AnxDs exhibited significantly higher total impairment scores on the M-ABC than controls, but were not significantly different from children with ADHD or children with comorbid AnxDs and ADHD. All clinical groups exhibited similar profiles of motor impairment. A total of 19 (46%) children with AnxDs scored below the 5th percentile on the M-ABC, indicating that motor function is impaired in many children with AnxDs to a degree that probably interferes with their activities of daily living. These results support the notion that assessment of motor function is important in understanding the daily challenges of children with AnxDs.


Application of 2- and 3-Dimensional Sonography Using the Virtual Organ Computer-Aided Analysis Technique to Measure the Hippocampal Formation and Its Correlation With Corrected Gestational Age in Neonates.
The purpose of this study was to use transcranial 2- and 3-dimensional sonography with the Virtual Organ computer-aided analysis (GE Healthcare, Milwaukee, WI) technique to observe the morphologic characteristics of the hippocampal formation and to analyze its correlation with the corrected gestational age. Transcranial sonography was performed from the sagittal plane of the anterior fontanel to the sagittal plane of the posterior horn of the lateral ventricle. The morphologic characteristics of the hippocampal formation in 183 singleton neonates with a corrected gestational age of 32 to 43 weeks were observed. The long diameter, short diameter, area, and perimeter of the hippocampal formation were all quantitatively measured. The volume of the hippocampal formation was measured by 3-dimensional sonography using the Virtual Organ computer-aided analysis technique. The correlation between the corrected gestational age and each parameter was analyzed. The display rate of the hippocampal formation was 100% in the neonates with a typical hippocampus shape. In healthy neonates with a corrected gestational age of 32 to 43 weeks, the long and short diameters, area, perimeter, and volume of the hippocampal formation were all positively correlated with the gestational age. Transcranial sonography could be used as a conventional approach for evaluation of the development of the hippocampal formation in neonates.


Reconstruction of stenotic or nonconfluent pulmonary arteries simultaneously with a Blalock-Taussig shunt.
Stenosis or discontinuity of the pulmonary arteries associated with congenital cardiac defects was repaired in 12 patients, in conjunction with the Blalock-Taussig shunt. This approach was based on the following concepts: (1) The shunted blood is more uniformly distributed to both lungs, which avoids predominance of flow to the ipsilateral lung and long-term pulmonary vascular damage; (2) because adequate blood flow is maintained, the contralateral lung growth will be near normal; (3) the possibility of future surgical correction is enhanced. The ages of the patients ranged from 2 to 24 months. Five had a primary diagnosis of tetralogy of Fallot, three had double outlet of the right ventricle, three had single ventricle, and one had a truncus type anomaly. All operations were performed without cardiopulmonary bypass. Dilation of the stenotic segment was performed in two patients, enlargement of the stenotic segment in three, and resection of the segment and end-to-end anastomosis in four. Nonconfluent pulmonary arteries were corrected in three patients. In one, the stenotic segment was resected and an anastomosis was made between the left pulmonary artery and pulmonary trunk. In another patient, a segment of the right subclavian artery was interposed between the pulmonary trunk and intrahilar left pulmonary artery. In the third patient, the right pulmonary artery was disconnected from the aorta and a tube was interposed between the right and left pulmonary arteries. There were no intraoperative or late deaths, and postoperative angiographic evaluations were satisfactory. We believe that in infants needing a Blalock-Taussig shunt the pulmonary artery anomalies, if present, should be corrected simultaneously.


Orientation and depth of surfactant protein B C-terminal helix in lung surfactant bilayers.
SP-B(CTERM) is a cationic amphipathic helical peptide and functional fragment composed of residues 63 to 78 of surfactant protein B (SP-B). Static oriented and magic angle spinning solid state NMR, along with molecular dynamics simulation was used to investigate its structure, orientation, and depth in lipid bilayers of several compositions, namely POPC, DPPC, DPPC/POPC/POPG, and bovine lung surfactant extract (BLES). In all lipid environments the peptide was oriented parallel to the membrane surface. While maintaining this approximately planar orientation, SP-B(CTERM) exhibited a flexible topology controlled by subtle variations in lipid composition. SP-B(CTERM)-induced lipid realignment and/or conformational changes at the level of the head group were observed using (31)P solid-state NMR spectroscopy. Measurements of the depth of SP-B(CTERM) indicated the peptide center positions ~8Å more deeply than the phosphate headgroups, a topology that may allow the peptide to promote functional lipid structures without causing micellization upon compression.


Cell type-specific expression of nuclear lamina proteins during development of Xenopus laevis.
The cell type-specific expression of the major nuclear lamina polypeptides ("lamins") during development of Xenopus was studied using two monoclonal antibodies (L(0)46F7: specific for LIII, the single lamin of oocytes; PKB8: specific for LI and LII of some somatic cells). In the oocyte, LIII localizes in the nuclear polymer, but upon nuclear envelope breakdown it is solubilized to a form sedimenting at 9 S. In early embryos, LIII contributes to nuclear lamina formation until its depletion. Correspondingly, LI and LII begin to be expressed at a specific point in embryogenesis and appear to be integrated with LIII into a common lamina structure. Later in development, LIII reappears as a prominent nuclear lamina protein but only in certain cells (neurons, muscle cells, and diplotene oocytes). We conclude that amphibian lamins represent a family of proteins expressed in relation to certain programs of cell differentiation.


Correction: Real-world comparison of clopidogrel, prasugrel and ticagrelor in patients undergoing primary percutaneous coronary intervention.
[This corrects the article DOI: 10.1136/openhrt-2018-000951.].


Inhibition of platelet-derived growth factor (PDGF) receptor affects follicular development and ovarian proliferation, apoptosis and angiogenesis in prepubertal eCG-treated rats.
The platelet-derived growth factor (PDGF) system is crucial for blood vessel stability. In the present study, we evaluated whether PDGFs play a critical intraovarian survival role in gonadotropin-dependent folliculogenesis. We examined the effect of intrabursal administration of a selective platelet-derived growth factor receptor (PDGFR) inhibitor (AG1295) on follicular development, proliferation, apoptosis and blood vessel formation and stability in ovaries from rats treated with equine chorionic gonadotropin (eCG). The percentages of preantral follicles (PAFs) and early antral follicles (EAFs) were lower in AG1295-treated ovaries than in control ovaries (p < 0.01-0.05). The percentage of atretic follicles (AtrFs) increased in AG1295-treated ovaries compared to control (p < 0.05). The ovarian weight and estradiol concentrations were lower in AG1295-treated ovaries than in the control group (p < 0.01 and p < 0.05, respectively), whereas progesterone concentrations did not change. AG1295 decreased the proliferation index in EAFs (p < 0.05) and increased the percentage of nuclei positive for cleaved caspase-3 and apoptotic DNA fragmentation (p < 0.01-0.05). AG1295 increased the expression of Bax (p < 0.05) without changes in the expression of Bcl-2 protein. AG1295-treated ovaries increased the cleavage of caspase-8 (p < 0.05) and decreased AKT and BAD phosphorylation compared with control ovaries (p < 0.05). AG1295 caused a decrease not only in the endothelial cell area but also in the area of pericytes and vascular smooth muscle cells (VSMCs) in the ovary (p < 0.05). Our findings suggest that the local inhibition of PDGFs causes an increase in ovarian apoptosis through an imbalance in the ratio of antiapoptotic to proapoptotic proteins, thus leading a larger number of follicles to atresia. PDGFs could exert their mechanism of action through an autocrine/paracrine effect on granulosa and theca cells mediated by PDGFRs. In conclusion, these data clearly indicate that the PDGF system is necessary for follicular development induced by gonadotropins.


Adapting the chronic disease model in the treatment of dually diagnosed patients.
This article suggests that while the focal point of inpatient treatment in the field of addiction should continue to be abstinence and 12-step programs, there should be considerable modification of the process of treatment. Many of the present inpatient psychiatric hospitals that treat addiction seem to be largely unaware of the biochemistry and physiology of early recovery. A model of treatment is proposed that takes into account the neurocognitive impairment and emotional augmentation that is present in early recovery. The focus of active treatment in this program is the treatment of the addictive process. The psychiatric diagnosis is managed through supportive psychotherapy and/or education if appropriate. Active treatment of the psychiatric diagnosis is deferred to outpatient treatment.


A Vascular Centered Surgical Approach to Radical Hysterectomy: Laparoscopic Anatomy of Pelvic Vascular System Revisited.
As a standard therapy for locally invasive cervical cancer, radical hysterectomy (RH) has been in routine medical practice for more than a century [1]. However, challenges still exist due to the troublesome bleeding during parametrium dissection and resection, which could increase the risk of surgical complications and may probably affect surgical outcomes ultimately [2]. This video illustrated the three-dimensional anatomy of the pelvic vascular system with particular emphasis on "deep uterine vein" and further introduced a vascular-centered surgical approach to performing RH, which could facilitate parametrium dissection with less blood loss and obtain enough resection margins. A step-by-step, narrated video demonstration SETTING: A university hospital INTERVENTIONS: After systemic pelvic lymphadenectomy, ureter was then identified along the medial leaf of the broad ligament. By continuously exploring the pelvic cavity along the ureter, communicating branches of the uterine artery to the ureter, urinary bladder, corpus uteri, uterine cervix, and upper vagina were clearly identified in a cranial to caudal direction, demonstrating the arterial network surrounding the urinary system. Coagulating and cutting these blood vessels could free the ureter from retroperitoneum and subsequently excavate the ureteral tunnel easily. Next, a precise dissection of the area below the ureter revealed the whole distribution of currently named "deep uterine vein". Originated from an internal iliac vein, it is much more like a venous confluence than an accompanying vein, with branches crossing directly into the bladder, dorsally to the rectum, and traveling caudally to the anterolateral side of the uterus and vagina in a crisscross fashion, which mandates us to describe it as pampiniform-like venous plexus instead of "deep uterine vein" due to its anatomical distribution and function. Finally, after complete exposure of venous network, enough extent of parametrium could be adequately separated and resected by accurate coagulation of blood vessels on an individualized requirement. Recognizing the precise anatomy of pelvic vascular system, especially the entire distribution of currently named "deep uterine vein" and isolating the venous branches connecting to all three parts of parametrium, are key to the RH procedure. Careful attention to the complex vascular anatomy is critical to reducing intraoperative bleeding and avoiding complications in RH.


Improvement of long-term preservation of isolated arrested rat heart: beneficial effect of the antiischemic agent trimetazidine.
Rat hearts, arrested in situ after intracaval injection of a simple mineral cardioplegic solution (St. Thomas), were preserved for 15 h at 4 degrees C either by simple immersion in the cardioplegic solution or low-flow perfusion by the same liquid (0.3 ml/min). Trimetazidine (TMZ) was added to the cardioplegic solution at a concentration of 10(-6) M in two additional groups corresponding to both preservation conditions. The biochemically determined ventricular ATP content was increased in immersed hearts by TMZ (+ 78%). The [ATP]/[Pi] ratio, as calculated from 31P nuclear magnetic resonance (NMR) spectroscopy, was significantly increased in both preservation conditions by TMZ: 0.08 +/- 0.03 versus 0.04 +/- 0.01 in immersed hearts and 0.53 +/- 0.13 versus 0.26 +/- 0.16 in perfused hearts (mean +/- SD). Intracellular pH was increased when TMZ was administered in perfused hearts (7.02 +/- 0.14 vs. 6.67 +/- 0.14, mean +/- SD). Functional recovery, estimated by the pressure developed by the left ventricle (intraventricular isovolumic balloon) when hearts were reperfused with a physiologic solution, was improved by TMZ in both preservation conditions: +137% in immersed hearts and +54% in perfused hearts. These results demonstrate that both the bioenergetic status of the myocardial cell and the functional capabilities of isolated, arrested, stored rat heart can be significantly improved by addition of the antiischemic drug TMZ to the preservation solution.


Taxonomic studies on the genus Ectatosticta (Araneae, Hypochilidae) from China, with descriptions of two new species.
Species of the spider family Hypochilidae Marx, 1888 from China are studied, including two known species and two new species of the genus Ectatosticta Simon, 1892. The new species are E. wukong sp. nov. (♂♀) from Sichuan and E. xuanzang sp. nov. (♀) from Tibet.