Some determinants of the time course of saccharin ingestion in hungry rats.
In rats that are food- but not water-deprived, a saccharin "meal" is characterized by a progressive decrease in lap rate as the bout progresses. However, saccharin does not trigger a fixed rate of lapping at any point in the sequence. When rats have only intermittent access to saccharin early in the session, they increase their rates of lapping so that, within each few minutes, the amount of lapping (or some correlate such as volume drunk) is held constant. This happens over a wide range of restriction conditions. And if compensation cannot occur during a period of constraint, then it occurs afterward, promptly and precisely. When constraint is withdrawn, rats drink amounts such that the total amount of drinking (or its correlate), through that point in the ingestive bout, is defended. These findings imply that the controlling system includes (1) an integrator that keeps track of the amount of drinking that has occurred, even across interruptions; and (2) a short-term feedback loop that operates minute by minute within the bout. This loop regulates, not the rate of lapping to be emitted, but the amount of lapping to be done (or its correlate); Thus the decline in responsiveness to saccharin as drinking progresses reflects a depression of this regulated value, not of lap rate per se.


Whole exome sequencing identified a novel LAMA2 frameshift variant causing merosin-deficient congenital muscular dystrophy in a patient with cardiomyopathy, and autism-like behavior.
Muscular dystrophy (MD) is a group of multiple muscle diseases, which causes severely impaired motor ability, degeneration and dysfunctions in the musculoskeletal system, respiratory failure and feeding difficulties. LAMA2-related MD is caused by pathogenic variants in the LAMA2 gene, encoding laminin a2 chain, a component of the skeletal muscle extracellular matrix protein laminin-α2β1γ1. We performed clinical examination and molecular genetic analysis in a patient with congenital MD (CMD), and autism-like phenotype. We performed whole exome sequencing (WES) to find possible genetic etiology of CMD in an Iranian non-consanguineous patient. The pathogenicity of the variants was assessed using various Bioinformatics tools. American College of Medical Genetics and Genomics (ACMG) guidelines were used to interpret the variant and Sanger sequencing in the patient and her family was applied for the confirmation of the variant. WES results showed a novel frameshift homozygous variant (p.Tyr1313LeufsTer4) in the LAMA2 gene leading to the CMD phenotype. This variant resides in a highly conserved region and was found to be co-segregating in the family. It fulfils the criteria of being pathogenic. We successfully identified a novel LAMA2 pathogenic variant in an Iranian patient suffering from CMD and autism using WES. Identification of disease-causing variant in autosomal recessive disorders such as CMD can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of the disease.


Surgical anatomy of supratentorial midline lesions.
In this paper the authors correlate the surgical aspects of deep median and paramedian supratentorial lesions with the connective fiber systems of the white matter of the brain. The cerebral hemispheres of 10 cadaveric brains were dissected in a mediolateral direction by using the fiber dissection technique, corresponding to the surgical approach. This study illuminates the delicacy of the intertwined and stratified fiber laminae of the white matter, and establishes that these structures can be preserved at surgical exploration in patients.


Primary Prevention of Mood Disorders: A Primary Concern That Requires Urgent Action.
Among mental disorders in youth, mood disorders contribute the greatest burden. With a multifactorial etiology and a developmental trajectory, mood disorders have myriad manifestations; hence, preventative approaches have to be equally diverse.


Clandestine existences and secret research: eliminating official discrimination in the Canadian military and going public in academia.
The 1990s was a notable decade for lesbians and gays in the Canadian military. Two important changes were the 1992 elimination of the official policy permitting discrimination against homosexual service members, and the 1996 introduction of benefits to same-sex partners. These changes radically influenced the psychological day-to-day reality of lesbian and gay military members. Yet, given the military culture, lesbian and gay members only began to come out in significant numbers at the turn of the century. This article presents an overview of our experience with researching the history of lesbians and gays in the Canadian military during the late 1990s and early years of the new century. It reveals the early clandestine nature of our research, and recounts some of the trials, tribulations, resistance, and successes we encountered when dealing with ethics boards and funding sources. It also describes our relationship with the media and how the military actively took steps to stall our efforts. We draw parallels between our experiences as researchers, and those of the lesbian service-members we were interviewing.


Lack of effect of fluoride on urinary cAMP excretion in rats.
The urinary excretion of cyclic 3'5'-adenosine monophosphate (cAMP) was measured in rats provided a low fluoride diet (less than 0.5 ppm) and drinking water containing either 0 or 25 ppm of fluoride. The pMole cAMP/microgram creatinine ratio decreased with age but was not influenced by fluoride intake.


Comprehensive MR angiography of the lower limbs: a hybrid dual-bolus approach including the pedal arteries.
The purpose of this study was to include the pedal vasculature into the coverage of peripheral multistation magnetic resonance angiography (3DceMRA). A total of 216 patients suffering from peripheral vascular disease were examined with a modified hybrid dual-bolus technique. The cruropedal arteries were acquired first with two sagittal slabs and time-resolved 3D sequences. Then the aortofemoral vessels were visualized using the bolus-chase technique and a second contrast injection. Interventional procedures were performed in 104 patients, and in 69 of those, the cruropedal vessels were also examined with digital subtraction angiography (iaDSA). Using 3DceMRA, the cruropedal arteries were displayed with both excellent and good quality in 95% (205/216 cases), and without any venous overlay in 94% (203/216 cases). The aortofemoral vessels were not jeopardized by the first contrast injection. With iaDSA as the standard of reference, observed sensitivity of 3DceMRA was found in ranges from 80% (29%, 99%) to 100% (86%, 100%) for assessing significant stenoses, and observed specificity ranged between 93% [80%, 98%] and 100% (82%, 100%). In conclusion, hybrid dual-bolus 3DceMRA significantly reduces the limitations of standard single-bolus 3DceMRA in anatomic coverage and temporal resolution of the cruropedal arteries, thus providing high-quality images of the entire peripheral vasculature.


Role of genetics in infection-associated arthritis.
Genetic discoveries in arthritis and their associated biological pathways spanning the innate and adaptive immune system demonstrate the strong association between susceptibility to arthritis and control of exogenous organisms. The canonical theory of the aetiology of immune-mediated arthritis and other immune-mediated diseases is that the introduction of exogenous antigenic stimuli to a genetically susceptible host sets up the environment for an abnormal immune response manifesting as disease. A disruption in host-microbe homeostasis driven by disease-associated genetic variants could ultimately provide the source of exogenous antigen triggering disease development. We discuss genetic variants impacting the innate and adaptive arms of the immune system and their relationship to microbial control and arthritic disease. We go on to consider the evidence for a relationship between HLA-B27, infection and arthritis, and then emerging evidence for an interaction between microbiota and rheumatoid arthritis.


Relationships of practitioner communications and characteristics with women's mammography use.
Women have reported not seeking mammography because their practitioners do not recommend it. The purposes of this study were to delineate which dimensions of practitioner communications and characteristics predicted women's mammography use. In a longitudinal, correlational design, participants were 797 mid-western women, aged 51-80 years, who had not had mammograms in the prior 13 months. Practitioner communications and characteristics and women's subsequent mammography use were assessed through telephone interviews with participants. Controlling for pre-existing differences, communications and characteristics were entered in a hierarchical logistic regression on mammography use. Practitioner-specific communications predicted mammography use (e.g. endorsement, encouragement, and assistance with scheduling) as well as having internists as identified practitioners. Practitioners' mammography-specific communications can promote mammography among women who have not used it often in the past. Practitioners--especially those who are not internists--can examine whether their interactions are conducive to fostering mammography use.


Analysis of two minimally invasive procedures for osteoporotic vertebral compression fractures with intravertebral cleft: a systematic review and meta-analysis.
A systematic review and meta-analysis to assess the pros and cons of percutaneous vertebroplasty (PVP) versus kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) with intravertebral cleft (IVC) including all available evidence from controlled trials. Databases including Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched to identify relevant studies comparing PVP and PKP for OVCFs with IVC. The outcomes mainly included visual analog scale (VAS), Oswestry Disability Index (ODI), local kyphotic angle (LKA), rate of vertebral height (VH%), and adverse events. Nine studies enrolling 688 patients were eligible for meta-analysis. The results indicated no significant differences between the two groups in the short-and long-term VAS, ODI, LKA, or VH% (P > 0.05). Compared with PVP, PKP was associated with significantly longer operation time (P < 0.05), higher cost (P > 0.05), and more injected cement volume (P < 0.05). In terms of adverse events, PKP has a lower risk of cement leakage (P < 0.05), while with no significant difference in adjacent-level fracture rates (P > 0.05). The two procedures have similar short- and long-term pain relief, functional recovery, local kyphosis correction, and vertebral height maintenance in OVCFs with IVC. PKP is superior to PVP for the injected cement volume, and lower cement leakage rate, however, with longer operation time, more fluoroscopy times, and higher cost. Further randomized controlled trials (RCTs) should be conducted to confirm these results.


Ten-year results of a randomised trial comparing cisplatin with cisplatin and cyclophosphamide in advanced, suboptimally debulked ovarian cancer.
176 eligible patients with advanced suboptimally operated ovarian carcinoma were randomly allocated to receive either cisplatin 75 mg/m2 or cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 (CP) every 28 days for six courses. The overall clinical response rates (complete response plus partial response) were 52 and 63% for CP and cisplatin, respectively (non-significant). Including results obtained by second-look laparotomy, we did not observe a statistically significant difference in response rates in the two treatment groups. Median progression-free survival was 10 and 11.9 months for CP and cisplatin, respectively (non-significant). No significant difference was observed in overall survival, with a median of 19.4 and 21.5 months for CP and cisplatin, respectively. Thirty-seven platinum-resistant and 27 platinum-sensitive tumours were treated with carboplatin or cisplatin as second-line therapy. Response rates to platinum second-line therapy were 6 and 50% for resistant and sensitive tumours, respectively (P < 0.001). This difference in response rate was also confirmed by survival analysis. Patients with platinum-sensitive tumours survived longer when they were treated with platinum-containing chemotherapy (P = 0.005). Median survival was 22.8 and 8.5 months after initiation of second-line treatment for the platinum-containing and platinum-free regimens, respectively. In summary, we observed in suboptimally operated ovarian carcinoma patients similar response rates, progression-free interval, and overall survival for equitoxic cisplatin and CP. However, the doses of cisplatin and cyclophosphamide chosen were substantially lower than current standard doses of CP. Our study demonstrates, therefore, that a suboptimal dose of CP is as effective as optimal dose monotherapy cisplatin. Patients with recurrences considered as platinum-sensitive had a significantly higher response rate and improved survival when retreated with platinum-containing therapy.


Long-term outcomes of an integrated transfusion reduction initiative in patients undergoing resection for colorectal cancer.
Perioperative blood transfusion in patients with colorectal cancer has been associated with increased cost, morbidity, mortality, and decreased survival. Five years ago, a transfusion reduction initiative (TRI) was implemented. We sought to evaluate the 5-year effectiveness and patient outcomes before and after the TRI. Patients who underwent colorectal resection for adenocarcinomas before (January 2006 to October 2009) and after the TRI (November 2009 to December 2013) were reviewed. A total of 484 patients were included; 267 and 217 patients were in the pre- and post-TRI groups, respectively. Decreased overall transfusion rates were sustained throughout the entire post-TRI era (17% vs 28%, P = .006). Three-year colorectal cancer disease-free survival rates were similar in the pre- and post-TRI eras at 85.3% (95% confidence interval [CI]: 79.9 to 89.3) and 81.6% (95% CI: 71.9 to 88.2), respectively. Three-year disease-free survival rate was lower in those receiving BTs vs those without BTs at 78.4% (95% CI: 65.7 to 86.8) vs 85.3% (95% CI: 80.4 to 89.1), respectively. A TRI remains a safe, effective way to reduce blood utilization in colorectal cancer surgery.


Key Characteristics of Database Studies on Drug Effectiveness in the Postmarketing Stage: A Systematic Review.
In recent years, real-world data (RWD) have been actively used in the field of pharmaceutical research. Database (DB) study, one of the observational studies using RWD, is a comprehensive, continuous, and rapid research method that plays an important role in the postmarketing stage of drugs, although the interpretation of the results may be limited. DB studies are often focused on drug safety, and previous research reviewing DB studies on drug effectiveness across different disease areas have been limited. The objective of this review was to reveal the current status of DB studies on drug effectiveness in various therapeutic areas and to provide information that allows researchers to consider conducting appropriate DB studies on drug effectiveness in the postmarketing stage. For this systematic review, we searched Embase and MEDLINE for DB studies on drug effectiveness published between 1 January 2018 and 31 December 2019. We reviewed the title, abstract, and methods to identify studies on drug effectiveness using medical information DBs, and excluded non-medical studies, studies on non-drug, and studies on drug safety, actual use, or cost outcomes that did not include any effectiveness outcomes. The name and type of the DB (administrative claims DB, clinical DB, pharmacy DB, and DB linkage), study design, comparison group, type of outcome, and presence or absence of reference to the outcome definition were extracted and summarized according to disease areas. We obtained 225 articles on DB studies on drug effectiveness using DBs that integrate large-scale medical data for secondary use across different disease areas. Among the DB classifications, administrative claims DBs (70%, 158/225) were most commonly used, while pharmacy DBs were used in only three studies. The largest number of reported studies were associated with cardiovascular, respiratory, and infectious diseases. Outcomes were often inpatient diagnosis, and some ideas included defining effectiveness based on drug use. While various outcomes were uniformly used in studies for the treatment of infectious diseases and respiratory organs, death (overall survival [OS]) and drug continuation (progression-free survival [PFS]) in patients with cancer, laboratory values in the endocrine system (mainly diabetes) were used as the main outcomes. Outcome validation within the article was limited. New user design (32%, 73/225), propensity score analysis (58%, 131/225), and sensitivity analysis (40%, 90/225) were used as measures to reduce bias in these studies. Sixty-eight studies (30%, 68/225) were supported by pharmaceutical companies. This systematic review summarized the status of cross-disease research articles on DB studies on drug effectiveness. While considering the strengths and limitations of DB studies, we hope that our comprehensive results would help to promote appropriate DB studies on drug effectiveness in the postmarketing stage.


Clinical management and molecular cytogenetic characterization in a 45,X/46,X,idic(Yp) patient with severe hypospadia.
Cryptorchidism and proximal hypospadia in a newborn are highly suspicious for an intersex disorder, and proper investigations should be planned immediately after birth. In some hypospadic patients, the presence of a palpable gonad in the scrotum may induce to assign the male sex, whereas the anatomy of internal and external genitalia could be extremely complex, requiring an accurate evaluation before any definitive attribution of gender. The authors present a case of an infant, referred to the hospital for surgical treatment of a proximal hypospadia, who showed ambiguous external genitalia, absence of the right gonad, a partially dysgenetic left testis, and presence of both müllerian and wolffian structures. Cytogenetic analysis detected a mosaicism with a cell line showing an isodicentric Yp chromosome and a second one, a 45, X chromosomal complement. Because the baby had been assigned previously to male gender, he underwent a staged masculinizing correction of the genital anomalies. The authors discuss the necessity of a careful evaluation of these patients at birth by a multispecialistic team, for appropriate sex assignment and for the assessment of the risk of neoplastic degeneration.


10-Year Experience with the Modified Pectoralis Major Flap: The Use of the Deltopectoral Flap to Reduce Skin Tension.
Purpose: Pectoralis major myocutaneous flap has been the work horse flap for head and neck reconstruction. However, due to the bulky nature of the pedicle it is not uncommon to struggle to achieve tension free closure of the neck skin incision. This case series presents a modified pectoralis major flap technique to overcome the difficulty of tight closure or the need to graft the residual cutaneous defect. Method: This 10-year study includes 73 patients who underwent modified pectoralis major flap reconstruction for complex laryngo-pharyngeal defects following resection of tumours involving larynx, hypopharynx oropharynx and cervical oesophagus. The modified technique involves accommodating a deltopectoral fasciocutaneous flap which rotates over the pedicle to insert into the neck incision providing extra tissue to achieve a tension free closure. Results: 73 patients underwent the procedure, 80% were male. Mean age of patients was 62.8years. Larynx was the most common site and the average size of the tumour was 34.8 mm. 13 patients developed minor complications such as wound dehiscence out of which 10 were managed conservatively, 3 patients required additional reconstructive procedures. 13 patients developed pharyngocutaneous fistula and 6 developed Neopharyngeal stenosis. 51 patients achieved good swallowing and 55 developed intelligible speech following recovery. Conclusion: We recommend the use of this technique as an effective method to achieve tension free neck incision closure and improved cosmetic results especially in centres which do not have free flap facility readily available.


Mechanism of the association between sleep quality and mortality in middle-aged and older adults: A prospective study analysis of the UK Biobank.
Although sleep quality is known to be associated with mortality, how poor sleep quality contributes to an increased risk of mortality is still unknown. We aimed to examine whether lifestyle, psychosocial and biological factors mediate the association. 205,654 participants from UK Biobank were used for the analysis. The outcome was all-cause, cardiovascular disease (CVD) and cancer mortality by February 2022. Exposure was assessed by a sleep score consisting of five sleep behaviors at baseline. Lifestyle, psychosocial, and biological factors are regarded as potential mediators. Mediation analysis based on Cox proportional hazards models was performed. Poor sleep quality was associated with a higher risk of all-cause (Hazard Ratio [HR] = 1.098; 95% CI: 1.058-1.140), CVD (HR = 1.139; 95% CI: 1.045-1.243) and cancer mortality (HR = 1.095; 95% CI: 1.040-1.152). Lifestyle mediators (smoking, physical activity, sedentary, BMI and diet) could explain between 2.6% and 34.0% of the increased risk of all-cause mortality in individuals with poor sleep quality. Self-reported health, frailty, depression, and loneliness were significant psychosocial mediators of this association pathway. About one-fifth of the association can be explained by the biological role of CRP. Similar mediating patterns were observed for CVD and cancer mortality. Both exposure and mediators were measured at baseline, so the possibility of reverse causality cannot be ruled out. Poor sleep quality is associated with an increased risk of death through a combination of lifestyle, psychosocial and biological pathways. Adopting healthy lifestyles and staying psychosocial well-being are cost-effective interventions to lower the risk of death.


Structure of chromatin containing extensively acetylated H3 and H4.
I have grown HeLa cells in 5 mM sodium n-butyrate leading to extensive in vivo histone acetylation, and have characterized the structure of chromatin containing the modified histones. Nuclear DNA in butyrate-treated cells is digested 5-10 fold more rapidly by DNAase I than the DNA of control cells. Staphylococcal nuclease degrades the two nuclear samples to acid-soluble material with identical rates; this nuclease, however, does excise nucleosomes with extensively acetylated histones from the nucleoprotein chain preferentially. The physical properties of unsheared chromatin and isolated core particles from control and butyrate-treated cells are closely similar, as are the rates of digestion of core particles from the two cell preparations by DNAase I. Determination of the relative susceptibilities of cleavage sites for DNAase I demonstrates that the site 60 bases from the ends of the DNA resistant in control cells, becomes susceptible to the nuclease in core particles containing acetylated histones. Similarly, the 5' terminal phosphate at the end of DNA in core prticles is removed by staphylococcal nuclease 2-3 fold faster in particles containing acetylated histones than in particles from control cells.


Target-flow inspiratory muscle training at home and during pulmonary rehabilitation in COPD patients with a ventilatory limitation during exercise.
The effects of a 10-week inspiratory muscle training (IMT) program at home were compared to IMT during a 10-week pulmonary rehabilitation program (PR) in 40 COPD patients with a ventilatory limitation of the exercise capacity. IMT was performed with a target-flow resistive device; the generated mouth pressure as well as the duty cycle were imposed. The mean age of the patients was 59, the mean FEV1 was 48% of predicted. In the training period the inspiratory muscle strength improved in both groups to the same degree. EMG fatigability of the diaphragm improved in the PR+ IMT group, but not in the IMT group. In the IMT group, the 12-min walking distance increased after the training period, but maximal workload (Wmax), VO2,max, and ADL scores did not change. In the PR + IMT group, however, Wmax, VO2,max, walking distance, and ADL scores improved significantly after the training period. Walking distance and ADL scores showed a significantly greater improvement in the PR + IMT group than in the IMT group. It is concluded that both isolated IMT and PR + IMT in COPD patients with a ventilatory limitation have a beneficial effect on inspiratory muscle strength, but PR + IMT improves the physical exercise capacity significantly more than IMT alone.


The validity of 9 physical tests for full-thickness rotator cuff tears after primary anterior shoulder dislocation in ED patients.
This study was undertaken to validate the diagnostic values of 9 different physical tests in emergency department patients with primary anterior shoulder dislocation (PASD) to select the best screening test for full-thickness rotator cuff tear (FTRCT) after PASD. A prospective analysis of 49 consecutive patients with x-ray-confirmed PASD was performed. All patients were followed at an average of 6.9 days (ranged from 4 to 10 days) in the emergency department. On the day of follow-up, 9 physical tests (namely, Jobe test, external rotation lag sign test, infraspinatus muscle strength test, dropping test, drop test, liftoff test, internal rotation lag sign test, belly-press test, and belly-off test) followed by shoulder ultrasound scan were performed to detect FTRCT. The prevalence of FTRCT after PASD is 37% (95% confidence interval [CI], 24%-52%). Fourteen percent of the patients with PASD were complicated with isolated supraspinatus tendon tear, whereas 22% were complicated with supraspinatus tendon tear combined with subscapularis and/or infraspinatus tendon tear. Jobe test has the highest sensitivity among the 9 physical tests being evaluated. The sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for positive test, and likelihood ratio for negative test of Jobe test as a screening test for FTRCT after PASD are 89% (95% CI, 64%-98%), 55% (95% CI, 36%-72%), 53% (95% CI, 35%-71%), 89% (95% CI, 65%-98%), 1.97 (95% CI, 1.29-2.99), and 0.20 (95% CI, 0.05-0.79), respectively. The prevalence of FTRCT after PASD is 37% (95% CI, 24%-52%). Jobe test has the highest sensitivity (89% CI, 64%-98%) among the tests.


Pyogranulomatous panniculitis in a cat associated with infection by the Mycobacterium fortuitum/peregrinum group.
A 6-year-old, spayed female, American domestic shorthair was presented with a 10-month history of nodules on the dorsum. Diagnosis of pyogranulomatous panniculitis caused by Mycobacterium fortuitum/peregrinum group was achieved by using tissue culture, chromatography, and histopathologic examination. Pathological findings, diagnosis, and clinical management of the condition are discussed.


Management of small intestinal bacterial overgrowth.
Similar to that of all mammals, the human gastrointestinal tract is colonized by 100 trillion bacteria shortly after birth. Remarkably, in the open-tube arrangement of the intestine, this bacterial population is tightly compartmentalized to the distal gut. Contamination of the small intestine with colonic bacterial flora or small intestinal bacterial overgrowth (SIBO) has been understood previously as a complication of uncommon conditions associated with obvious intestinal stasis. However, SIBO has also been found in 78% to 84% of patients with the common condition of irritable bowel syndrome (IBS). In this paper, the diagnostic and treatment approaches to SIBO are reconsidered within the larger framework of the patient with IBS.


Characterisation of HlyC and mechanism of activation and secretion of haemolysin from E. coli 2001.
In this paper the DNA sequence of the cloned hlyC gene from E. coli 2001 is presented. The gene encodes a protein of 20 kDa which is able to activate the 107 kDa polypeptide encoded by hlyA. This gives rise to a haemolytically active protein which differs from the inactive form in stability and by its migration when analysed by polyacrylamide gel electrophoresis under non-denaturing conditions. We also show that the inactive form is secreted in the presence of the transport functions hlyB and hlyD. This result rules out any role for the hlyC gene product in the transport of HlyA across the inner membrane.


Fatty acid profile of beef from immunocastrated (BOPRIVA(®)) Nellore bulls.
Twenty Nellore bulls (ABW=357.7±9.65kg) were divided into 2 groups: intact and immunocastrated - Bopriva®. After the trial period, the cattle were slaughtered and carcass fat thickness was evaluated, ether extract and fatty acid composition of the longissimus thoracis analyses were performed, and the activity indices of relevant enzymes were calculated. The means were calculated and compared by Student's t-test and Pearson's correlation coefficients (p<0.05). The immunocastrated group showed higher back fat thickness, ether extract, monounsaturated fatty acids (MUFAs), and activity index of Δ(9) desaturase C18 and lower polyunsaturated fatty acids (PUFAs) and n-6 fatty acids when compared to the intact group. The correlations between ether extract and the saturated and monounsaturated fatty acids were positive, and negative with polyunsaturated, n-3, n-6 and PUFA/SFA. Therefore, immunocastration may improve the fatty acid profile in the longissimus thoracis by increasing MUFAs, mainly oleic acid that is the most representative fatty acid in the meat and is considered beneficial to health.


Superior vena cava syndrome associated with uterine serous carcinoma.
•Extensive nodal metastases from uterine serous carcinoma can lead to SVC syndrome.•Prevention of nodal metastases is an important goals of care discussion.•Radiation, steroids and/or chemotherapy must all be considered in this setting.


Wernicke Encephalopathy in a Pediatric Patient with Avoidant Restrictive Food Intake Disorder: A Rare Presentation of Thiamine Deficiency.
BACKGROUND Wernicke encephalopathy is traditionally associated with chronic alcoholism, nutritional imbalance, prolonged intravenous feeding, hyperemesis, anorexia nervosa, and malabsorption syndromes. We report a case of Wernicke's encephalopathy in a 12-year-old girl with avoidant restrictive food intake disorder. CASE REPORT The patient had lost 45.4 kg of body weight due to self-imposed changes to her diet, before presenting with decreased oral intake for 2-3 weeks, intermittent nausea, crampy epigastric pain, and post-prandial emesis. Her weight on admission was 78.2 kg. She received intravenous fluids of dextrose 5% with normal saline while she initially attempted to eat, but the post-prandial emesis persisted. She developed a fear of vomiting, which led to even more severe food intake restriction. After a week, she began to report double vision and blurred peripheral vision, with physical findings of nystagmus and an ataxic gait. She was empirically started on thiamine after negative neurology workup, with improvement of her gait, blurry vision, and nystagmus. Thiamine deficiency was later confirmed. CONCLUSIONS In patients with large amounts of weight loss presenting with neurological symptoms, Wernicke's encephalopathy must be considered in the differential diagnosis. Avoidant restrictive food intake disorder is rarely reported to cause Wernicke's encephalopathy. To the best of our knowledge, this is the first pediatric case demonstrating that Wernicke encephalopathy can occur in this type of eating disorder and not just in anorexia nervosa.


Flocculation, coagulation, and precipitation of manure affecting three separation techniques.
The effects of polymer flocculation before manure separation were investigated, through testing both a linear and a branched polymer. Centrifugation removed 60% of phosphorus from raw manure (control), whereas raw manure clogged the filters during gravity drainage and pressure filtration. At optimum flocculation, 95% of phosphorus was removed using any of the three methods. Optimum flocculation was achieved when 2.8meq of polymer charge was added per kg of manure, corresponding to 0.6g/kg of highly charged, branched polymer or 0.85g/kg of less-charged, linear polymer. If 10mmol of ferric chloride was added per kg of manure, 2% more phosphorus was precipitated and removed. The linear polymer formed loose flocs and was superior for reducing turbidity, whereas the branched polymer formed compact flocs that deflocculated at high polymer doses. The branched polymer, however, was best for pressure filtration, as overdosing with the linear polymer resulted in high resistance.


Epigenetic Modification-Associated Molecular Classification of Gastric Cancer.
Epigenetic modification is involved in tumorigenesis and cancer progression. We developed an epigenetic modification-associated molecular classification of gastric cancer (GC) to identify signature genes that accurately predict prognosis and the efficacy of immunotherapy. Least absolute shrinkage and selection operator and multivariate Cox regression analysis were conducted to develop an epigenetic modification-associated molecular classification. We investigated the significance of PIP4P2, an independent prognostic factor of the classification system, in predicting the prognosis and immunotherapy efficacy of patients with GC. The epigenetic modification-associated molecular classification was highly associated with the clinicopathological characteristics of patients and the existing classification of GC. PIP4P2 was highly expressed in GC tissue and tumor-associated macrophages. High PIP4P2 expression in GC tissue-induced tumor progression by activating PI3K/AKT signal transduction had a negative impact on immunotherapy efficacy. High expression of PIP4P2 in macrophages was correlated with poor prognosis in patients with GC. PIP4P2 is an independent unfavorable prognostic factor of epigenetic modification-associated molecular classification, is involved in tumorigenic progression, and is essential for assessing the prognosis and immunotherapy efficacy of GC.


Oxygen-selective adsorption on high-silica LTA zeolite.
The adsorption capacity of O2 and N2 on a LTA-type zeolite can be significantly affected by the change of its Si/Al ratio. With the increase in Si/Al ratio and the decrease in the amount of Na+, the protonated high-silica LTA zeolite changes from being a N2-selective sorbent to an O2-selective sorbent to reverse the O2 and N2 selectivity.


Medical liaisons for continuity of head and neck cancer care.
The role of assistance in coordinating treatment and follow-up on the effectiveness and reliability of long-term care of head and neck cancer patients was evaluated. A comparison between the Department of Radiation Oncology, where a liaison team assists cancer patients, and the Department of Otolaryngology, where there were no such personnel, was made. Of 124 consecutive patients with head and neck squamous cell carcinoma, 31 were treated with surgery alone and 93 had radiation therapy alone or in combination with surgery. Patients were nearly equally divided among stages, although a higher percentage receiving surgery were stage I and those receiving radiation were stage IV. Nineteen radiation patients and 1 surgery patient have died; this is consistent with the differences in stage distribution. Thirteen of 31 surgery patients had unreliable follow-up, with 7 lost to follow-up. Only 8 of 93 radiation patients were unreliable, with 4 lost. The difference is statistically significant. The importance of nursing/social work liaisons in coordinating treatment and follow-up of head and neck cancer patients is discussed.


A multimodal sensor dataset for continuous stress detection of nurses in a hospital.
Advances in wearable technologies provide the opportunity to monitor many physiological variables continuously. Stress detection has gained increased attention in recent years, mainly because early stress detection can help individuals better manage health to minimize the negative impacts of long-term stress exposure. This paper provides a unique stress detection dataset created in a natural working environment in a hospital. This dataset is a collection of biometric data of nurses during the COVID-19 outbreak. Studying stress in a work environment is complex due to many social, cultural, and psychological factors in dealing with stressful conditions. Therefore, we captured both the physiological data and associated context pertaining to the stress events. We monitored specific physiological variables such as electrodermal activity, Heart Rate, and skin temperature of the nurse subjects. A periodic smartphone-administered survey also captured the contributing factors for the detected stress events. A database containing the signals, stress events, and survey responses is publicly available on Dryad.


Long term expression of bicistronic vector driven by the FGF-1 IRES in mouse muscle.
Electrotransfer of plasmid DNA into skeletal muscle is a promising strategy for the delivery of therapeutic molecules targeting various muscular diseases, cancer and lower-limb ischemia. Internal Ribosome Entry Sites (IRESs) allow co-expression of proteins of interest from a single transcriptional unit. IRESs are RNA elements that have been found in viral RNAs as well as a variety of cellular mRNAs with long 5' untranslated regions. While the encephalomyocarditis virus (EMCV) IRES is often used in expression vectors, we have shown that the FGF-1 IRES is equally active to drive short term transgene expression in mouse muscle. To compare the ability of the FGF-1 IRES to drive long term expression against the EMCV and FGF-2 IRESs, we performed analyses of expression kinetics using bicistronic vectors that express the bioluminescent renilla and firefly luciferase reporter genes. Long term expression of bicistronic vectors was also compared to that of monocistronic vectors. Bioluminescence was quantified ex vivo using a luminometer and in vivo using a CCD camera that monitors luminescence within live animals. Our data demonstrate that the efficiency of the FGF-1 IRES is comparable to that of the EMCV IRES for long term expression of bicistronic transgenes in mouse muscle, whereas the FGF-2 IRES has a very poor activity. Interestingly, we show that despite the global decrease of vector expression over time, the ratio of firefly to renilla luciferase remains stable with bicistronic vectors containing the FGF-1 or FGF-2 IRES and is slightly affected with the EMCV IRES, whereas it is clearly unstable for mixed monocistronic vectors. In addition, long term expression more drastically decreases with monocistronic vectors, and is different for single or mixed vector injection. These data validate the use of bicistronic vectors rather than mixed monocistronic vectors for long term expression, and support the use of the FGF-1 IRES. The use of a cellular IRES over one of viral origin is of particular interest in the goal of eliminating viral sequences from transgenic vectors. In addition, the FGF-1 IRES, compared to the EMCV IRES, has a more stable activity, is shorter in length and more flexible in terms of downstream cloning of second cistrons. Finally, the FGF-1 IRES is very attractive to develop multicistronic expression cassettes for gene transfer in mouse muscle.


Inflammaging and the Skin.
As global life expectancy continues to rise, we are challenged with maintaining health into old age. One strategy is to target the chronic low-level inflammation associated with aging, termed inflammaging. This is characterized by increased levels of circulating proinflammatory cytokines and a shift toward cellular senescence, changes that are believed to drive many age-associated conditions, including dementia, arthritis, and type 2 diabetes. As with other organs, the skin undergoes functional decline during aging, becoming more fragile and susceptible to infection; however, the contribution of inflammaging is not well-understood. This review article describes the evidence for inflammaging in the skin, its relationship with senescence, and how this relates to declining skin structure and function.


[Substantiation of the use of pepsidil in secretory insufficiency of the digestive glands caused by antitubercular drugs].
The experiments on rats were undertaken to study the action of pepsidil to make up for the biosynthesis deficiency of digestive enzymes in the stomach and pancreas caused by antituberculous drugs (methazide + PAS, isoniazid + PAS, isoniazid + rifampicin + ethambutol). It was proved that pepsidil reduced an inhibiting action of antituberculous drugs on the activity of gastroenteric tract proteinases. The given condition should be taken into account when antituberculous treatment is conducted.


Characterization and measurement of immunoglobulins in the grey seal (Halichoerus grypus).
Immunoglobulin concentrations were measured in the serum and colostrum of adult and pup Grey seals from North Rona in the outer Hebrides and the Isle of May in the Firth of Forth. IgG was shown to be the main immunoglobulin and two subclasses were identified. Serum immunoglobulin content was low in the week-old pups and increased up to 5 weeks, although it remained substantially lower than in the adults. Colostral immunoglobulins were high and cannot explain the low values in the pup serum. It is considered that the increased opportunistic infections seen in Grey seal pups may be related to this low immunoglobulin status.


The relation of serum 25-hydroxyvitamin-D levels with severity of obstructive sleep apnea and glucose metabolism abnormalities.
Obstructive sleep apnea (OSA) and 25-hydroxyvitamin-D₃ (25-OH-D) deficiency are two separate disorders associating with obesity, inflammation, and impaired glucose metabolism. We aimed to investigate the vitamin D status of OSA patients regarding to potential links between lower vitamin D levels and abnormal glucose metabolism, which is one of the main adverse outcomes of OSA. Study group is composed of 190 non-diabetic subjects who were suspected of having OSA. Subjects undergone polysomnography and were grouped due to apnea-hypopnea indices (AHI) as controls (AHI < 5, n = 47), mild OSA (5 ≤ AHI < 15, n = 46), moderate OSA (15 ≤ AHI < 30, n = 47), and severe OSA (AHI ≥ 30, n = 50). Serum 25-OH-D, HbA₁c, insulin levels were measured and 75-g oral glucose tolerance test was performed. Serum 25-OH-D level (ng/ml) of OSA patients were lower than control subjects (17.4 ± 6.9 vs. 19.9 ± 7.8), and decrement was parallel to severity of OSA; as 18.2 ± 6.4 (5 ≤ AHI < 15), 17.5 ± 7.4 (15 ≤ AHI < 30), and 16.3 ± 6.9 (AHI > 30), respectively (P = 0.097, r = -0.13). However, severe female OSA patients had significantly lower 25-OH-D levels (11.55 ng/ml), while control males had the highest mean value (21.7 ng/ml) (P < 0.001). Frequency of insulin resistance (IR) was 48%, prediabetes 41%, diabetes 16% in OSA patients. Mean 25-OH-D level of insulin resistant subjects (HOMA-IR ≥ 2.7, n = 77, AHI = 35.5) was lower than non-insulin resistant subjects (HOMA-IR < 2.7, n = 113, AHI = 19.8) as 16.18 ± 7.81 versus 19.2 ± 6.6, respectively (P = 0.004). 25-OH-D level of 91 non-diabetic subjects (n = 91, AHI = 19.7) was 19.5 ± 7.4, prediabetics (n = 75, AHI = 28.7) was 17.45 ± 6.9, and diabetics (n = 24, AHI = 46.3) was 13.8 ± 5.3 (P = 0.02). We showed that subjects with more severe OSA indices (AHI ≥ 15) tended to present lower vitamin D levels correlated to increased prevalence of IR, prediabetes, and diabetes. Vitamin D deficiency may play a role and/or worsen OSA's adverse outcomes on glucose metabolism. OSA patients may be considered for supplementation treatment which was shown to ameliorate abnormal glucose metabolism and inflammation.


Anatomic considerations for posterior iliac crest bone procurement.
The aim of this study was to identify the relative anatomic locations of relevant vital structures at risk for injury during posterior iliac crest bone graft procurement. Twenty-one cadavers yielded 39 intact posterior ilia for dissection. The posterior superior iliac spine (PSIS) was used as the primary reference landmark. Measurements were made to the medial branch of the superior cluneal nerves, the superior branch of the middle cluneal nerves, the sciatic notch, and the superior gluteal vessels. Distances from the spinal midline to the superior cluneal nerves were recorded. The average distances from the PSIS to the superior and middle cluneal nerves, greater sciatic notch, and superior gluteal vessels were 5.7 cm (standard deviation, 1.22 cm), 6.55 cm (standard deviation, 1.53 cm), 5.3 cm (standard deviation, 0.71 cm), and 5.4 cm (standard deviation, 0.95 cm), respectively. The most medial superior cluneal nerve was identified at 3.0 to 4.9 cm from the PSIS in 23% of cases, at 5.0 to 6.9 cm from the PSIS in 61.5% of cases, and farther than 7.0 cm from the PSIS in 15.4% of cases. This study illustrates that the most medial superior cluneal nerve is often closer to the PSIS than previously described and the same holds true for the greater sciatic notch and superior gluteal vessels. Knowledge of the anatomic locations of these important structures should allow the surgeon to avoid or decrease the complication rate of bone procurement from the posterior ilium.


[Combined use of TUVP and TURP for prostate cancer with bladder outlet obstruction].
To investigate a new surgical method for the treatment of prostate cancer with bladder outlet obstruction. Forty-seven patients with prostate cancer complicated with bladder outlet obstruction were treated by combined use of transurethral electrovaporization ablation of the prostate (TUVP) and transurethral resection of the prostate (TURP). The operations were successful, with satisfactory results and no serious complication. IPSS decreased from (26.5 +/- 4.8) pre-operatively to (8.5 +/- 2.2) post-operatively (P < 0.05); Qmax increased from (4.6 +/- 1.5) ml/s to (14.5 +/- 3.6) ml/s (P < 0.05); and PSA decreased from (58.1 +/- 7.2) microg/L to (3.6 +/- 1.8) microg/L (P < 0.01). The combined use of TUVP and TURP is a safe and ideal method for the treatment of prostate cancer with bladder outlet obstruction.


Phenylalanine hydroxylase from Legionella pneumophila is a thermostable enzyme with a major functional role in pyomelanin synthesis.
Legionella pneumophila is a pathogenic bacterium that can cause Legionnaires' disease and other non-pneumonic infections in humans. This bacterium produces a pyomelanin pigment, a potential virulence factor with ferric reductase activity. In this work, we have investigated the role of phenylalanine hydroxylase from L. pneumophila (lpPAH), the product of the phhA gene, in the synthesis of the pyomelanin pigment and the growth of the bacterium in defined compositions. Comparative studies of wild-type and phhA mutant corroborate that lpPAH provides the excess tyrosine for pigment synthesis. phhA and letA (gacA) appear transcriptionally linked when bacteria were grown in buffered yeast extract medium at 37°C. phhA is expressed in L. pneumophila growing in macrophages. We also cloned and characterized lpPAH, which showed many characteristics of other PAHs studied so far, including Fe(II) requirement for activity. However, it also showed many particular properties such as dimerization, a high conformational thermal stability, with a midpoint denaturation temperature (T(m)) = 79 ± 0.5°C, a high specific activity at 37°C (10.2 ± 0.3 µmol L-Tyr/mg/min) and low affinity for the substrate (K(m) (L-Phe) = 735 ± 50 µM. lpPAH has a major functional role in the synthesis of pyomelanin and promotes growth in low-tyrosine media. The high thermal stability of lpPAH might reflect the adaptation of the enzyme to withstand relatively high survival temperatures.


Gut microbes regroup to aid defence after infection.
Resident gut microbes can help to block infection, but the mechanisms involved are not fully understood. It has now been found that changes in the microbial community after infection boost the level of a molecule that combats harmful bacteria.


Derivation of induced pluripotent stem cell SJTUi003-A from a 69-year-old Chinese Han Sporadic Alzheimer's disease patient with APOEε3/ε4 genetic background.
Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease. In this study, we generated an induced pluripotent stem cell (iPSC) line from the dermal fibroblasts of a 69-year-old female patient carrying APOEε3/ε4 allele and diagnosed with sporadic AD. The iPSC line will be a useful tool for investigating the pathogenesis mechanisms and for drug tests in AD.


A Case Report of a Rare Heterozygous Variant in the Desmin Gene Associated With Hypertrophic Cardiomyopathy and Complete Atrioventricular Block.
Hypertrophic cardiomyopathy (HCM) is the primary cause of sudden cardiac death in children and adolescents. Patients with HCM frequently have ventricular tachycardia and ventricular fibrillation, although complete atrioventricular block (CAVB) is very rare. We report a case of HCM with CAVB in an 8-year-old girl who underwent transvenous implantable cardioverter-defibrillator placement after resuscitation. In this patient, we identified a de novo heterozygous missense variant, Arg406Trp (c.1216C > T), in the desmin (DES) gene. Pathogenic variants in the DES gene result in cardiomyopathy, conduction disorders, and skeletal muscle weakness. This recently identified variant may cause HCM with CAVB.


Alzheimer' s disease, oxidative stress and gammahydroxybutyrate.
Although the cause of Alzheimer's disease is unknown, oxidative stress, energy depletion, excitotoxicity and vascular endothelial pathology are all considered to play a part in its pathogenesis. In reaction to these adverse events, the Alzheimer brain appears to deploy a highly conserved biological response to tissue stress. Oxidative metabolism is turned down, the expression of antioxidative enzymes is increased and intermediary metabolism is shifted in the direction of the pentose phosphate shunt to promote reductive detoxification, repair and biosynthesis. Gathering evidence suggests that the release of beta-amyloid and the formation of neurofibrillary tangles, the two hallmarks of Alzheimer's disease, are components of this protective response. Gammahydroxybutyrate (GHB), an endogenous short chain fatty acid, may be able to buttress this response. GHB can reduce glucose utilization, shift intermediary metabolism in the direction the pentose phosphate shunt and generate NADPH, a key cofactor in the activity of many antioxidative and reductive enzymes. GHB has been shown to spare cerebral energy utilization, block excitotoxicity and maintain vascular integrity in the face of impaired perfusion. Most important, GHB has repeatedly been shown to prevent the tissue damaging effects of oxidative stress. It may therefore be possible to utilize GHB to strengthen the brain's innate defences against the pathological processes operating in the Alzheimer brain and, in this way, stem the advance of Alzheimer's disease.


Residual control of isometric finger forces in hemiparetic patients. Evidence for dissociation of performance deficits.
Dissociation of performance in the control of isometric finger forces was observed in 6 patients with left-sided unilateral lesions involving sensorimotor areas. In a precision task subjects had to maintain, under visual feedback, a low constant force (2.5 N) while holding a force transducer between thumb and index finger. Performance was compared with that in a speed task, where changes had to be produced, as rapidly as possible, between two prescribed forces (6.25 and 18.75 N). While there were severe deficits in fast force changes corresponding to the functional impairment of the right hand in all patients, right hand maintenance of low isometric force remained intact in the same patients.


Regional changes in coaptation geometry after reduction annuloplasty for functional mitral regurgitation.
While it is known that band annuloplasty for functional mitral regurgitation (FMR) improves leaflet coaptation, the effect on regional coaptation geometry has not previously been well defined. We used three-dimensional transesophageal echocardiography (3D-TEE) to analyze the regional effects of semirigid band annuloplasty on annular geometry and leaflet coaptation zones of patients with FMR. Sixteen patients with severe FMR underwent a semirigid band annuloplasty. Intraoperative full volume 3D-TEE datasets were acquired pre valve and post valve repair. Offline analysis assessed annular dimensions and regional coaptation zone geometry. The regions were defined as R1 (A1-P1), R2 (A2-P2), and R3 (A3-P3); coaptation distance, coaptation depth, and coaptation length were measured in each region. Differences were analyzed with repeated measures within a general linear model. Band annuloplasty decreased mitral regurgitation grade from 3.7 to 0.1 (scale 0 to 4). Annular septolateral dimension (p<0.01) and coaptation distance (p<0.01) decreased significantly in all regions. Likewise, anterior and posterior leaflet coaptation lengths increased in all regions (p<0.01 and p=0.05, respectively), with region 2 showing the greatest increase (p=0.01). Changes in coaptation depth were not significant. Semirigid band annuloplasty for FMR produces significant regional remodeling of leaflet coaptation zones, with region 2 showing the greatest increase in leaflet coaptation length. This regional analysis of annular geometry and leaflet coaptation creates a framework to better understand the mechanisms of surgical success or failure of annuloplasty for FMR.


LOW BIRTH WEIGHT BABIES : INCIDENCE AND RISK FACTORS.
In a prospective hospital based study, during the period from Jan 95 to Dec 96, 3100 consecutively delivered live newborns were studied for the incidence of low birth weight neonates and to evaluate the associated risk factors. One thousand fourteen newborns were classified as low birth weight babies. The incidence expressed per 1000 live births was 327 (32.7%). Of these, 815 (80.4%) were small for gestational age neonates and 199 (19.6%) were preterm neonates. Five hundred seventy small for gestational age neonates (70%) were weighing between 2001 to 2500 gms. Mothers belonging to the age group of 19-25 years delivered the maximum number of low birth weight babies (618/1014) and of these 82.8% were small for gestational age neonates. There were 48 neonates with low birth weight born to mothers below the age of 18 years. Primiparous mothers were found to contribute higher number of low birth weight neonates (414/1014). Spacing as a factor did not show any major difference. Two hundred sixty two low birth weight neonates were born to mothers with significant obstetrical problems such as pregnancy induced hypertension, bad obstetrical history and premature rupture of membranes. The incidence of 32.7% of low birth weight babies is high enough to ring alarm bells.


Diagnostic challenges and forensic implications in a case of infantile fatal myocarditis.
We present the case of a 23-month-old child who died less than 24 h after the onset of cardiac symptoms, despite being admitted to the hospital 72 h earlier. Autopsy revealed no significant macroscopic changes, and histologic examination revealed focal lymphocytic myocarditis with myocyte disruption, diffuse alveolar damage in the exudative phase, and generalized lymphocytic immune activation in other organs. Ante-mortem and post-mortem microbiological exams did not clearly prove a causative role of infectious agents. The peculiarity of this case was characterized by the contrast between the severe clinical features and the mild cardiac histological findings. This discrepancy, coupled with the suspicion of a viral causative role based on both ante-mortem and post-mortem microbiological examinations, presented significant challenges in reaching an etiological diagnosis. This case also confirms that the diagnosis of myocarditis in children cannot be made solely on the basis of histological cut-offs or microbiological results. Using abductive reasoning, various diagnostic hypotheses were formulated and evaluated to arrive at the final diagnosis of fatal myocarditis of viral or post-viral origin. Data from post-mortem examination are often the only source of information that is available to the experts, especially in cases of sudden infant death syndrome. In such cases, the forensic pathologists should accurately evaluate findings that may appear to indicate a different etiology, and, in the absence of clinical or radiological data, interpret post-mortem data in a logically correct manner. The autopsy is the first essential step to evaluate the cause of death and must be integrated with the results of ante- and post-mortem diagnostic tests in a holistic approach, which is crucial to allow forensic pathologists to provide an appropriate and relevant opinion.


Comparison of gastric lavage and thoracic cavity lavage in the treatment of severe hypothermia in dogs.
A study was undertaken to compare warm gastric (Group 1) and closed thoracic cavity (Group 2) lavage for rewarming severely hypothermic dogs. Adult mongrel dogs were monitored by intra-arterial catheter, central venous catheter, and ECG, and by central venous, esophageal, and rectal temperature probes. Animals were externally cooled to an average of 21.2 C using ice bags. Eight Group 1 and eight Group 2 animals underwent continuous warm saline gastric or closed thoracic cavity lavage, respectively, using afferent and efferent nasogastric and thoracostomy tubes. No animal suffered ventricular fibrillation during tube placement. The closed lavage system consisted of a high-efficiency heat exchanger, a roller pump infusion device, and a heat exchange fluid bath. The lavage fluid circulated at a flow rate of 550 mL/min and a temperature of 39 C. Thoracic lavage animals were followed clinically for 24 hours for evidence of complications, then euthanized and autopsied. The mean time required to rewarm the animals 10 C by central venous temperature probe was 210.9 +/- 18.6 minutes for the gastric group and 99.3 +/- 23.0 minutes for the thoracic group (P less than .001). Rectal temperature consistently lagged behind central venous temperature during both the cooling and rewarming phases in both treatment groups. All of the thoracic lavage animals made an uneventful recovery. Continuous warm saline thoracic cavity lavage for core rewarming of severely hypothermic dogs is more effective than gastric lavage, and appears to be safe.(ABSTRACT TRUNCATED AT 250 WORDS)


Urological management of spina bifida (including management of urinary tract infections).
Active and ongoing surveillance for urological problems helps to minimize the impact of the major source of mortality and morbidity in spina bifida.


Bipartite synchronization in coupled delayed neural networks under pinning control.
This paper considers the bipartite leader-following synchronization in a signed network composed by an array of coupled delayed neural networks by utilizing the pinning control strategy and M-matrix theory, where the communication links between neighboring nodes of the network can be either positive or negative. Under the assumption that the node-delay is bounded and differentiable, a sufficient condition in terms of a low-dimensional linear matrix inequality is derived for reaching bipartite leader-following synchronization in the signed network, based on which a simple algebraic formula is further given to estimate an upper bound of the node-delay. When the node-delay is bounded and non-differentiable, some criteria are established by using the descriptor method and the reciprocally convex approach such that the bipartite leader-following synchronization problem for the signed network can be successfully solved. Finally, numerical simulations are provided to illustrate the effectiveness of theoretical analysis.


Therapeutic efficacy of infliximab on patients with short duration of Crohn's disease: a Japanese multicenter survey.
This study was designed to evaluate the efficacy of infliximab in patients with Crohn's disease of durations less than one year. Two nationwide surveys of 35 Japanese institutions majoring in inflammatory bowel disease identified 41 patients with active Crohn's disease who were treated by infliximab within 12 months after the diagnosis (E-group) and 97 patients treated later during their clinical course (L-group). Clinical features, responses to infliximab, and accompanying medications were compared between the two groups. A decrease in Crohn's disease activity index > or = 70 or the index < 150 two weeks after infliximab was regarded to be efficacious. The age was younger (24 vs. 33 years, median, P < 0.0001) and intestinal stricture (12 vs. 49 percent, P < 0.0001), internal fistula (0 vs. 26 percent, P = 0.0003), and previous intestinal resection (7 vs. 57 percent, P < 0.0001) were less frequent in the E-group than in the L-group. The efficacy of infliximab was different between the two groups with a significantly higher value in the E-group than in the L-group (90 vs. 61 percent, P = 0.0012). A multivariate logistic regression analysis revealed nonstricturing intestinal lesion to be a significant factor related to the efficacy of infliximab. Infliximab is more efficacious in Crohn's disease with short duration, probably because of less frequent stenosis.


Differentiation of pilocytic astrocytoma, medulloblastoma, and hemangioblastoma on diffusion-weighted and dynamic susceptibility contrast perfusion MRI.
This study aimed to evaluate the diagnostic performance of dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging and apparent diffusion coefficient (ADC) for differentiating common posterior fossa tumors, pilocytic astrocytoma (PA), medulloblastoma (MB), and hemangioblastoma (HB). Between January 2016 and April 2022, we enrolled 23 (median age, 7 years [range, 2-26]; 12 female), 13 (10 years [1-24]; 3 female), and 12 (43 years [23-73]; 7 female) patients with PA, MB, and HB, respectively. Normalized relative cerebral blood volume and flow (nrCBV and nrCBF) and normalized mean ADC (nADCmean) were calculated from volume-of-interest and statistically compared. nADCmean was significantly higher in PA than in MB (PA: median, 2.2 [range, 1.59-2.65] vs MB: 0.93 [0.70-1.37], P < .001). nrCBF was significantly higher in HB than in PA and MB (PA: 1.10 [0.54-2.26] vs MB: 1.62 [0.93-3.16] vs HB: 7.83 [2.75-20.1], all P < .001). nrCBV was significantly different between all 3 tumor types (PA: 0.89 [0.34-2.28] vs MB: 1.69 [0.93-4.23] vs HB: 8.48 [4.59-16.3], P = .008 for PA vs MB; P < .001 for PA vs HB and MB vs HB). All tumors were successfully differentiated using an algorithmic approach with a threshold value of 4.58 for nrCBV and subsequent threshold value of 1.38 for nADCmean. DSC parameters and nADCmean were significantly different between PA, MB, and HB. An algorithmic approach combining nrCBV and nADCmean may be useful for differentiating these tumor types.


The Femoral Sulcus Deepening Trochleoplasty of Lyon.
The sulcus deepening trochleoplasty procedure has been described for the management of patellofemoral instability in patients with severe trochlear dysplasia. Here, we describe the updated Lyon sulcus deepening trochleoplasty technique. This technique with a stepwise approach allows one to prepare the trochlea, remove the subchondral bone, osteotomize the articular surface, and fix the facets with 3 anchors while minimizing the risk of complications.


Environmental intervention in a university canteen with focus on decision guidance: An evaluation study regarding food consumption, nutrient intake, perception, and satisfaction by canteen users.
An environmental intervention with focus on Decision Guidance was implemented in a university canteen. It comprised the offer of a health promoting food option (HPFO), including a health promoting lunch option and health promoting snacks. Possible changes of food consumption and nutrient intake of student canteen users (substudy A), perception of the HPFO by canteen users (substudy B.1), and possible changes of their satisfaction regarding the canteen (substudy B.2) at least 10 weeks after the start of the intervention were examined. Substudy A used a controlled pretest-posttest-design (paired sample). The students were assigned to intervention group (canteen visits ≥ once/week, n = 27) or control group (canteen visits < once/week, n = 39). Substudy B.1 used a cross-sectional design, and substudy B.2 a pretest-posttest-design (paired sample). Only canteen users (≥once/week) were included (substudy B.1 n = 89, substudy B.2 n = 30). Food consumption and nutrient intake did not change (p > 0.05) in the intervention group versus control group (substudy A). In substudy B.1 canteen users were aware of the HPFO, appreciated it highly, and were satisfied with it. In substudy B.2 canteen users were at posttest more satisfied regarding service and health value of offered lunches (p < 0.05). Although the HPFO was positively percepted, no effects on the daily diet were observed. The offered proportion of the HPFO should be increased.


Attitudes of surgical nurses towards pressure ulcer prevention.
Nurses play the key role in prevention of pressure ulcers, and negative attitudes of them may affect preventive care strategies. This research aimed to identify surgical nurses' attitudes towards pressure ulcer prevention. A descriptive and cross-sectional study design was used to collect data between March 31-May 16, 2016 on 101 voluntary nurses (66.01% of all nurses) working in surgical units of a university hospital in Turkey. "Attitude towards Pressure Ulcer Prevention Instrument" and "Nurse Information Form" were used to investigate nurses' attitude toward preventing pressure ulcer. Descriptive statistics, Mann-Whitney U test, independent samples t-test, Pearson's chi-squared, and correlation tests were used to analyse the data. The mean age of nurses' was 32.0 ± 6.3 years and, the average duration of clinical experience was 72.3 ± 61 months. A total of 54.5% were working in surgical wards and, 40.6% gained additional education about pressure ulcer care. The mean total attitude score was found to be 80.5% (41.8 ± 4.8). Previous education significantly affected the total attitude score of nurses (p < 0.05). The total scale score showed that surgical nurses had a positive attitude towards pressure ulcer prevention and nurses who had previous education about pressure ulcer care has higher attitude score than who had not. It is recommended that effective in-service education programs be developed at hospitals or that nurses be required to attend courses to help them to improve their pressure ulcer care.


Metalloproteases and their inhibitors are altered in both torn and intact rotator cuff tendons.
We evaluated the role of matrix metalloproteases (MMPs) and their inhibitors which are involved in extracellular matrix remodeling and degradation, in the pathogenesis of chronic rotator cuff tears. Tendon samples were harvested from 13 patients who underwent arthroscopic repair of a rotator cuff tear. Supraspinatus biopsy specimens were harvested en bloc from the arthroscopically intact middle portion of the tendon more than 1 cm from the torn edge, from the lateral edge of the tear, and from the superior one third of the macroscopically intact subscapularis tendon used as control. Histological analysis and an evaluation of the activity of specific metalloproteases and the tissue inhibitors of metalloprotease (TIMP-1, TIMP-2) was done blindly by multiplex sandwich ELISA (Search-Light technology) in each specimen Histological evidence of tendinopathy was present in all patients with a tear of the rotator cuff, and not in the macroscopically intact subscapularis tendon. There was a significant increase in MMP 1, MMP 2, MMP 3 and in TIMP-1, TIMP-2 levels in all specimens examined, including the macroscopically intact portion of the supraspinatus tendon and in the control specimens The tissue in the ruptured area of the supraspinatus tendon undergoes marked rearrangement at molecular levels. This involves the activity of MMP 1, 2 and 3, and supports the critical role of MMPs in the tendon physiology. Seemingly intact parts of the injured supraspinatus tendon can present tendinopathic features, with altered cellular metabolism.


Heteromorphic sex chromosomes of lizardfish (Synodontidae): focus on the ZZ-ZW1W2 system in Trachinocephalus myops.
The karyotype and DNA content of four lizardfish species (family Synodontidae), that is, Saurida elongata, Synodus ulae, Synodus hoshinonis and Trachinocephalus myops, were analyzed. The karyotype of T. myops significantly differed from that of the other three species having diploid chromosome number of 48 with mainly acrocentric chromosomes and the ZZ-ZW sex chromosome system. The chromosome number of male T. myops was 2n = 26, while that of female T. myops was 2n = 27. The karyotype consisted of 11 pairs of metacentrics, one pair of acrocentrics and, in addition, two large metacentrics in the male and a single large metacentric, a distinctly small subtelocentric and a microchromosome in the female. C-banding demonstrated that in the female the subtelocentric chromosome and the microchromosome were heterochromatic. The karyotype of T. myops was thought to be derived from a 48 chromosome type synodontid fish through the involvement of Robertsonian rearrangement; the rearrangement of the sex chromosomes proceeded during karyotype evolution. Among the chromosomes, the large metacentrics were determined to be neo-Z (a fusion of the original Z and an autosome), the microchromosomes the W1 (originally W), and the subtelocentric chromosomes the W2 (derived from an autosome pair). The miniaturization of W1 and W2 chromosomes and their heterochromatinization suggested that sex chromosomes in this species have been already highly differentiated. The findings on DNA content implied that the karyotype of T. myops evolved by centric fusion events without loss in DNA amount.


Too much or too little step width variability is associated with a fall history in older persons who walk at or near normal gait speed.
Decreased gait speed and increased stride time, stride length, double support time, and stance time variability have consistently been associated with falling whereas step width variability has not been strongly related to falls. The purpose was to examine the linear and nonlinear associations between gait variability and fall history in older persons and to examine the influence of gait speed. Gait characteristics and fall history were obtained in 503 older adults (mean age = 79; 61% female) participating in the Cardiovascular Health Study who could ambulate independently. Gait characteristics were recorded from two trials on a 4 meter computerized walkway at the subject's self-selected walking speed. Gait variability was calculated as the coefficient of variation. The presence of a fall in the past 12 months was determined by interview. The nonlinear association between gait variability and fall history was examined using a simple three level classification derived from the distribution of the data and from literature based cut-points. Multivariate logistic regression was used to examine the association between step width variability (extreme or moderate) and fall history stratifying by gait speed (1.0 m/s) and controlling for age and gender. Step length, stance time, and step time variability did not differ with respect to fall history (p > .33). Individuals with extreme step width variability (either low or high step width variability) were more likely to report a fall in the past year than individuals with moderate step width variability. In individuals who walked > or = 1.0 m/s (n = 281), after controlling for age, gender, and gait speed, compared to individuals with moderate step width variability individuals with either low or high step width variability were more likely to have fallen in the past year (OR and 95% CI 4.38 [1.79-10.72]). The association between step width variability and fall history was not significant in individuals who walked < 1.0 m/s (n = 224). Extreme (either too little or too much) step width variability is associated with falls in the past year in older persons who walk at or near normal gait speed and not in older persons who walk slowly (< 1.0 m/s).


Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease.
To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting. A multicentre observational study investigated adverse events, treatment discontinuation, FEV1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV1 below 40% predicted. Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment. The mean absolute change in FEV1 was +2.06% after one month of treatment (P=0.086) and +3.19% after 3 months (P=0.009). BMI was unchanged. Treatment with lumacaftor/ivacaftor in patients with CF and severe lung disease was discontinued more frequently than reported in clinical trials, due to respiratory AEs. Nevertheless, the patients who continued treatment had an increase in lung function comparable to what was observed in pivotal trials.


Prospective intra-patient evaluation of a shoulder retraction device for radiotherapy in head and neck cancer.
Irradiation of tumors in the larynx and pharynx is often technically challenging in patients with a short neck or high shoulders. Shoulder retraction devices can sometimes resolve this problem and allow irradiation via lateral beam directions. This study aimed to measure the proportion of patients who would benefit from such an approach and to quantify the magnitude of the benefit obtained. Twenty patients were studied. Simulator images were obtained before and after intervention. The additional exposure of the cervical spine was measured. Patient comfort and acceptability were assessed with a questionnaire. Improvement of exposure of the cervical spine was observed in 80% of patients. In 20%, there was either no difference or the position was worse. Shoulder retraction exposed a mean of 8.4-10.2 mm more of the cervical spine. Patients in general reported the device as comfortable. The use of a shoulder retraction device produced clinically significant improvements in exposure of the tissues of the cervical spine and neck and should be considered in patients being irradiated for tumors arising in the larynx or hypopharynx.


Shear Wave Elastography on the Uterine Cervix: Technical Development for the Transvaginal Approach.
This research aimed to identify biological and technical confounders in the nonpregnant cervix when applying shear wave elastography with an endovaginal transducer. Cervical speed measurements were obtained at the internal and external os in the anterior and posterior portions of the cervix using a transvaginal approach in 69 nongravid patients. Reliable measurements were obtained at the external os and internal os, anteriorly and posteriorly, in 63, 55, 55, and 26 patients, respectively. The mean speed obtained at the external os, anteriorly and posteriorly, was 2.52 ± 0.49 m/s and 2.87 ± 0.63 m/s, respectively, and at the internal os, anteriorly and posteriorly, 3.29 ± 0.79 m/s and 4.10 ± 1.11 m/s, respectively. The difference in speed between all regions was statistically significant (P < .05). Ultrasound-induced artifacts appear to affect the transmission of the elastographic main pulse, with cervical position contributing to suboptimal shear wave production in the posterior cervix. Reliable shear wave propagation can be achieved in the anterior cervix in most patients.


The Gα-interacting vesicle-associated protein interacts with and promotes cell surface localization of GRP78 during endoplasmic reticulum stress.
Cell surface translocation of the chaperone glucose-regulated protein 78 kDa (GRP78) is a key event that promotes cancer cell survival during endoplasmic reticulum (ER) stress. Here, we identify Gα-interacting vesicle-associated protein (GIV) - an enhancer of prosurvival signaling during ER stress - as a binding partner of GRP78. We show that GIV and GRP78 interact in an ER stress-dependent manner through their respective carboxyl terminal domains and that GIV aids in the localization of GRP78 to the plasma membrane. Kaplan-Meier analysis of disease-free survival in cancer patients shows poor prognosis for patients with high expression of both GIV and GRP78, further suggesting a vital role for these two proteins in enhancing cancer cell viability.


Isoprene Reactivity on Water Surfaces from ab initio QM/MM Molecular Dynamics Simulations.
Isoprene is the most abundant volatile organic compound in the atmosphere after methane. While gas-phase processes have been widely studied, the chemistry of isoprene in aqueous environments is less well known. Nevertheless, some experiments have reported unexpected reactivity at the air-water interface. In this work, we have carried out combined quantum-classical molecular dynamics simulations of isoprene at the air-water interface, as well as ab initio and density functional theory calculations on isoprene-water complexes. We report the first calculation of the thermodynamics of adsorption of isoprene at the water surface, examine how hydration influences its electronic properties and reactivity indices, and estimate the OH-initiated oxidation rate. Our study indicates that isoprene interacts with the water surface mainly through H-π bonding. This primary interaction mode produces strong fluctuations of the π and π* bond stabilities, and therefore of isoprene's chemical potential, nucleophilicity and ionization potential, anticipating significant dynamical effects on its reactivity at the air-water interface. Using data from the literature and free energies reported in our work, we have estimated the rate of the OH-initiated oxidation process at the air-water interface (5.0×1012 molecule cm-3 s-1 ) to be about 7 orders of magnitude larger than the corresponding rate in the gas phase (8.2×105 molecule cm-3 s-1 ). Atmospheric implications of this result are discussed.


Vertical distribution of radionuclides in soil of a grassland site in Chernobyl exclusion zone.
Five soil profiles from a site about 8 km SE of the Chernobyl NPP were investigated for the vertical distribution of radionuclides. The average (137)Cs-inventory at the site is about 2.6 MBq/m(2) (reference date 1 May 1986). Apart from (137)Cs, the following radionuclides have been identified (their activity ratios to (137)Cs in brackets): (134)Cs (0.537), (125)Sb (0.068), (60)Co (0.0022), (154)Eu (0.016), (155)Eu (0.020), (94g)Nb (9.5E-5), (239/240)Pu (0.0088), (238)Pu (0.040), (90)Sr (0.30) and (241)Am (0.011). Apparent vertical migration velocities are between 0.14 and 0.26 cm/a, apparent dispersion coefficients range from 0.02 to 0.13 cm(2)/a. The rankings of the velocities v for different radionuclides are (Sr, Cs, Sb, Co, Pu)< Am < Eu and Sr < (Cs, Nb), for D, the following rankings have been found: (Nb, Sr, Cs) < Am < Eu, Cs<Sb and Nb<Co (all on p = 0.1 level).


Clinical Features of Patients With Acute Aortic Dissection After an Earthquake: Experience from the Kumamoto Earthquake 2016.
While there is a concern about the increase in the occurrence of acute aortic dissection (AAD) caused by the worsening of hypertension, mental stress, etc., there is a lack of data regarding the influence of disasters on this event. The aim of this study was to address this issue in the acute-subacute phase after the Kumamoto Earthquake occurred on 14 April 2016. We retrospectively investigated the impacts of the Kumamoto Earthquake on various cardiovascular diseases, including AAD, utilizing the medical records of patients in 16 hospitals in Kumamoto Prefecture during the period from 14 April to 30 June (78 days) in 2014, 2015, 2016, and 2017. The occurrence of heart failure and venous thromboembolism increased significantly in the acute-subacute phase after the earthquake. When comparing the earthquake year (2016) to the non-earthquake years (2014, 2015, and 2017), the difference in the occurrences and mortalities of AADs were not significant. When other characteristics of the patients were compared between the earthquake year and the non-earthquake years, there were no differences. It might be possible that the Kumamoto Earthquake did not affect the incidence of AAD or deaths from AAD, possibly because the climate was mild and the preventive efforts based on previous experience were successful. University Hospital Medical Information Network (UMIN)-CTR (http://www.umin.ac.jp/ctr/). UMIN000023864. Opt-out materials were available at the following website: http://www.kumadai-junnai.com/home/wp-content/uploads/shinsai.pdf.


Lattice calculation of the lowest-order hadronic contribution to the muon anomalous magnetic moment.
We present a quenched lattice calculation of the lowest order [O(alpha(2))] hadronic contribution to the anomalous magnetic moment of the muon which arises from the hadronic vacuum polarization. A general method is presented for computing entirely in Euclidean space, obviating the need for the usual dispersive treatment which relies on experimental data for e(+)e(-) annihilation to hadrons. While the result is not yet of comparable precision to those state-of-the-art calculations, systematic improvement of the quenched lattice computation to this level is straightforward and well within the reach of present computers. Including the effects of dynamical quarks is conceptually trivial; the computer resources required are not.


Effect of a nurse team coordinator on outcomes for hospitalized medicine patients.
Several randomized trials have found that discharge planning improves outcomes for hospitalized patients. We do not know if adding a clinical nurse specialist (CNS) to physician teams in hospitals that already have discharge planning services makes a difference. In 2 teaching hospitals, patients were randomly assigned to regular hospital care or care with a clinical nurse specialist. The clinical nurse specialist facilitated hospital care by retrieving preadmission information, arranging in-hospital consultations and investigations, organizing postdischarge follow-up visits, and checking up on patients postdischarge with a telephone call. In-hospital outcomes included mortality and length of stay. Postdischarge outcomes included time to readmission or death, patient satisfaction, and the risk of adverse event. Adverse events were poor outcomes due to medical care rather than the natural history of disease. A total of 620 sequential patients were randomized (CNS n = 307, control n = 313), of which 361 were followed after discharge from hospital (CNS n = 175, control n = 186). The groups were similar for the probability of in-hospital death (CNS 9.3% vs control 9.7%) or being discharged to the community (58.0% vs 60.0%). The groups did not differ for postdischarge outcomes including readmission or death (21.6% vs 15.6%; P = 0.16) or risk of adverse event (23.6% vs 22.8%). Mean [SD] patient ratings of overall quality of care on a scale of 10 was higher in the clinical nurse specialist group (8.2 [2.2] vs 7.6 [2.4]; P = 0.052). The addition of a clinical nurse specialist to a medical team improved patient satisfaction but did not impact hospital efficiency or patient safety.


Sleep Apnea Screening for Commercial Drivers: A Retrospective Comparison of the 2016 FMCSA MRB Recommendations and the 2006 Joint Task Force Consensus Guidelines.
Compare the 2016 Federal Motor Carrier Safety Administration (FMCSA) and 2006 Joint Task Force (JTF) Guidelines for commercial drivers' obstructive sleep apnea (OSA) screening. Retrospective review of all commercial driver medical examinations performed in 2017 at an academic occupational medicine clinic. Screening criteria from both the JTF and FMCSA were applied, separately, and jointly. Statistical tests were applied as appropriate. Applying the FMCSA or JTF criteria separately to 706 commercial drivers, the positive OSA screening yields were 15.7% and 16.9%, respectively. Using both criteria produced an overall positive OSA screen yield of 20.1%. Positive predictive values for applying both guidelines ranged from 72.7% to 95.5%. The combined use of the 2016 FMCSA and 2006 JTF OSA screening criteria in series has a higher screening yield than using either guideline individually.


Zerovalent Fe, Co and Ni nanoparticle toxicity evaluated on SKOV-3 and U87 cell lines.
We have considered nanoparticles (NPs) of Fe, Co and Ni, three transition metals sharing similar chemical properties. NP dissolution, conducted by radioactive tracer method and inductively coupled plasma mass spectrometry, indicated that NiNPs and FeNPs released in the medium a much smaller amount of ions than that released by Co NPs. The two considered methodological approaches, however, gave comparable but not identical results. All NPs are readily internalized by the cells, but their quantity inside the cells is less than 5%. Cytotoxicity and gene expression experiments were performed on SKOV-3 and U87 cells. In both cell lines, CoNPs and NiNPs were definitely more toxic than FeNPs. Real-time polymerase chain reaction experiments aimed to evaluate modifications of the expression of genes involved in the cellular stress response (HSP70, MT2A), or susceptible to metal exposure (SDHB1 and MLL), or involved in specific cellular processes (caspase3, IQSEC1 and VMP1), gave different response patterns in the two cell lines. HSP70, for example, was highly upregulated by CoNPs and NiNPs, but only in SKOV-3 cell lines. Overall, this work underlines the difficulties in predicting NP toxicological properties based only on their chemical characteristics. We, consequently, think that, at this stage of our knowledge, biological effects induced by metal-based NPs should be examined on a case-by-case basis following studies on different in vitro models. Moreover, with the only exception of U87 exposed to Ni, our results suggest that metallic NPs have caused, on gene expression, similar effects to those caused by their corresponding ions.


Anti-angiogenic properties of a sulindac analogue.
Angiopoietins (Ang) are crucial for new blood vessel formation and exert their effects by acting on the Tie2 receptor. We have recently described a sulindac analogue 2-((1E,Z)-1-benzylidene-5-bromo-2-methyl-1H-inden-3-yl)acetic acid; termed C-18 from now onwards) that inhibits Tie2 receptor activity in kinase assays in vitro. Here, we have assessed the ability of C-18 to inhibit angiogenesis-related properties of endothelial cells and tested its selectivity for the Tie2 receptor. For in vitro experiments human umbilical vein endothelial cells (HUVEC) were used. Proliferation was measured using the MTT assay; migration assays were performed in a modified Boyden chamber and tube-like structure formation was determined on matrigel. The effects of C-18 in vivo were evaluated in the chicken chorioallantoic membrane (CAM). Pre-treatment of HUVEC with C-18 blocked Ang-1-stimulated migration, but also abolished vascular endothelial cell growth factor (VEGF)- and fibroblast growth factor 2-induced responses. Incubation with C-18 inhibited serum-induced proliferation in a concentration-dependent manner; C-18 was, however, without effect on Ang-1-induced survival. In addition, we observed that C-18 did not inhibit ligand-induced receptor phosphorylation of Tie2 or VEGFR2. On the other hand, C-18 blocked activation of members of the mitogen-activated protein kinase family and of the Ser/Thr kinase Akt induced by both VEGF and Ang-1. Furthermore, incubation of CAMs with C-18 led to a dose-dependent inhibition of vascular length. C-18 did not act as a Tie2 inhibitor, as originally thought, but rather inhibited growth factor-stimulated signalling pathways that regulate endothelial cell migration and potently reduces neovascularization in vivo.


KIR2DS4, KIR2DL2, and KIR2DS4del are linked with basaloid tumors, lymph node metastasis, advanced stage and metastatic risk in head and neck squamous cell carcinoma.
Our previous study has suggested that KIR2DS1, 2DS5, 3DS1 and KIR2DL5 are associated with head and neck squamous cell carcinoma (HNSCC) development. The purpose of the current study was to investigate the possible association of killer cell immunoglobulin like receptors (KIRs) gene with the clinicopathological features of patients. We reviewed the pathological reports of 285 pathologically confirmed cases of HNSCC and analyzed the association of KIR system with pathological characteristics. A significant increase was demonstrated in the carrier frequency of KIR2DS4 in conventional than basaloid type and a higher frequency of lymph node metastasis (LNM) in carriers of KIR2DL2 and individuals possess 5 inhibitory KIRs (iKIRs). We also observed a higher proportion of patients with advanced stage of HNSCC in carriers of KIR2DL2 and deleted variant of KIR2DS4. In HNSCC, KIR2DL2 is positively while KIR2DS4 is negatively associated with advanced stage. The higher proportion of LNM in carriers of KIR2DL2 and carriers of 5 iKIRs, suggested that inhibitory KIRs are associated with metastatic risk.


Trends and outcomes of outpatient total shoulder arthroplasty after its removal from CMS's inpatient-only list.
In January 2021, the US Medicare program approved reimbursement of outpatient total shoulder arthroplasties (TSA), including anatomic and reverse TSAs. It remains unclear whether shifting TSAs from the inpatient to outpatient setting has affected clinical outcomes. Herein, we describe the rate of outpatient TSA growth and compare inpatient and outpatient TSA complications, readmissions, and mortality. Medicare fee-for-service claims for 2019-2022Q1 were analyzed to identify the trends in outpatient TSAs and to compare 90-day postoperative complications, all-cause hospital readmissions, and mortality between outpatients and inpatients. Outpatient cases were defined as those discharged on the same day of the surgery. To reduce the COVID-19 pandemic's impact and selection bias, we excluded 2020Q2-Q4 data and used propensity scores to match 2021-2022Q1 outpatients with inpatients from the same period (the primary analysis) and from 2019-2020Q1 (the secondary analysis), respectively. We performed both propensity score-matched and -weighted multivariate analyses to compare outcomes between the two groups. Covariates included sociodemographics, preoperative diagnosis, comorbid conditions, the Hierarchical Condition Category risk score, prior year hospital/skilled nursing home admissions, annual surgeon volume, and hospital characteristics. Nationally, the proportion of outpatient TSAs increased from 3% (619) in 2019Q1 to 22% (3456) in 2021Q1 and 38% (6778) in 2022Q1. A total of 55,166 cases were identified for the primary analysis (14,540 outpatients and 40,576 inpatients). Overall, glenohumeral osteoarthritis was the most common indication for surgery (70.8%), followed by rotator cuff pathology (14.6%). The unadjusted rates of complications (1.3 vs 2.4%, P < .001), readmissions (3.7 vs 6.1%, P < .001), and mortality (0.2 vs 0.4%, P = .024) were significantly lower among outpatient TSAs than inpatient TSAs. Using 1:1 nearest matching, 12,703 patient pairs were identified. Propensity score-matched multivariate analyses showed similar rates of postoperative complications, hospital readmissions, and mortality between outpatients and inpatients. Propensity score-weighted multivariate analyses resulted in similar conclusions. The secondary analysis showed a lower hospital readmission rate in outpatients (odds ratio: 0.8, P < .001). There has been accelerated growth in outpatient TSAs since 2019. Outpatient and inpatient TSAs have similar rates of postoperative complication, hospital readmission, and mortality.


Parkinson's disease pathogenesis, evolution and alternative pathways: A review.
Sporadic Parkinson's disease (PD) is one of the most common neurodegenerative diseases of the elderly. In the scientific literature, surveys aiming to investigate the potential diagnostic biomarkers for PD have focused on skin and intestinal tissue biopsies, whereas more recent studies have reported an association between PD and skin disorders, such as seborrheic dermatitis and rosacea. In addition, a connection between PD and Crohn's disease has been established. These data suggest the hypothesis of a possible link between the gastrointestinal tract and skin and the development of PD. In fact, the nervous system, gastrointestinal tract and skin are analogous in their embryological development and, therefore, have molecular networks and pathogenic pathways in common. Based on these data, it may be assumed that the gastrointestinal tract and skin might be implicated in the pathogenesis of PD. The evolutionary hypothesis might also be a useful tool for further investigations into the overlap across neurological, gastrointestinal and skin disorders.


The correlation between follicular measurements, oocyte morphology, and fertilization rates in an in vitro fertilization program.
To explore the relationship between follicle size and the morphology of the oocyte-cumulus-corona complex with fertilization rates in stimulated cycles of IVF. Retrospective comparison of measurements and observations of 2,429 oocytes from 215 patients undergoing 324 stimulated IVF cycles. A large hospital-based IVF program. Individual follicles were measured by ultrasound before transvaginal aspiration and the size was recorded. The oocyte-cumulus-corona complex from each follicle was examined and classified. The oocytes were checked for evidence of fertilization 17 to 22 hours after insemination. The fertilization rate of all oocytes regardless of morphological type revealed a positive linear correlation with increasing follicle diameter. The fertilization rates of type I oocytes was marginally higher than type II oocytes, controlling for follicle diameter; however, this difference did not achieve statistical significance. Oocytes from follicles with a mean diameter > or = 16 mm had significantly higher fertilization rates than did oocytes from follicles with a mean diameter < or = 14 mm. Follicle size is a better predictor of fertilization than is morphological characterization of the oocyte-cumulus-corona complex in IVF.


Use of procainamide with rapid atrial pacing for successful conversion of atrial flutter to sinus rhythm.
Rapid atrial pacing is a useful technique and often the therapy of choice to terminate atrial flutter in patients. However, interruption of atrial flutter by rapid atrial pacing may not always produce sinus rhythm, but rather may result in atrial fibrillation. Twelve patients with spontaneous atrial flutter that had been present for greater than 24 h were studied to assess the efficacy of atrial pacing, alone and in combination with procainamide, to convert atrial flutter to normal sinus rhythm. Rapid atrial pacing for greater than or equal to 15 s from selected atrial sites at selected pacing rates were performed during atrial flutter. The initial pacing rate was always at a cycle length 10 ms shorter than the atrial flutter cycle length. If atrial flutter persisted after cessation of pacing, it was repeated at progressively shorter cycle lengths until either a rate of 400 beats/min was achieved or atrial fibrillation was induced. In two patients, atrial flutter was converted to sinus rhythm with pacing alone. Three patients developed sustained atrial fibrillation as a result of the rapid atrial pacing, this rhythm ultimately reverting back to atrial flutter in two. Ten patients received procainamide and 9 of the 10 had lengthening of the atrial flutter cycle length by a mean of 68 ms (1 patient continued to have atrial fibrillation). Then, using the same atrial pacing protocol, high right atrial pacing alone at a mean cycle length of 227 ms interrupted atrial flutter in all these patients, returning their rhythm to sinus rhythm. It is concluded that intravenous procainamide effectively augments the efficacy of rapid atrial pacing to convert atrial flutter to sinus rhythm.


Tenosuspension of the Reflected Head of the Rectus Femoris in Hip Arthroscopy: Description of a Portal and a Surgical Maneuver.
Arthroscopy is a surgical technique useful in the treatment of intra- and extra-articular hip pathologies, including femoroacetabular impingement (FAI). In the arthroscopic treatment of pincer-type FAI, tendon interposition of the reflected head of the rectus femoris frequently hinders acetabular edge resection in the anterior-superior region (acetabuloplasty) and labrum repositioning, even causing tendon injury during the surgical procedure. Many surgeons do not give importance to the reflected head of the rectus femoris, and during the procedure they try to avoid it, giving 30° of flexion to the hip. However, this does not always prevent tendon injury caused by the instruments. Some surgeons even resect part of the tendon to improve visualization or to use it as a labral graft. The objective of this work is to describe a reproducible surgical maneuver that allows to perform the anterior-superior acetabular edge resection and chondrolabral union repair with less damage to the reflected head of the rectus femoris.