K-Mer-Based Genome Size Estimation in Theory and Practice.
Recent advances in sequencing technologies have made genome sequencing of non-model organisms with very large and complex genomes possible. The data can be used to estimate diverse genome characteristics, including genome size, repeat content, and levels of heterozygosity. K-mer analysis is a powerful biocomputational approach with a wide range of applications, including estimation of genome sizes. However, interpretation of the results is not always straightforward. Here, I review k-mer-based genome size estimation, focusing specifically on k-mer theory and peak calling in k-mer frequency histograms. I highlight common pitfalls in data analysis and result interpretation, and provide a comprehensive overview on current methods and programs developed to conduct these analyses.


NUDT6 and NUDT9, two mitochondrial members of the NUDIX family, have distinct hydrolysis activities.
The 22 members of the NUDIX (NUcleoside DIphosphate linked to another moiety, X) hydrolase superfamily can hydrolyze a variety of phosphorylated molecules including (d)NTPs and their oxidized forms, nucleotide sugars, capped mRNAs and dinucleotide coenzymes such as NADH and FADH. Beside this broad range of enzymatic substrates, the NUDIX proteins can also be found in different cellular compartments, mainly in the nucleus and in the cytosol, but also in the peroxisome and in the mitochondria. Here we studied two members of the family, NUDT6 and NUDT9. We showed that NUDT6 is expressed in human cells and localizes exclusively to mitochondria and we confirmed that NUDT9 has a mitochondrial localization. To elucidate their potential role within this organelle, we investigated the functional consequences at the mitochondrial level of NUDT6- and NUDT9-deficiency and found that the depletion of either of the two proteins results in an increased activity of the respiratory chain and an alteration of the mitochondrial respiratory chain complexes expression. We demonstrated that NUDT6 and NUDT9 have distinct substrate specificity in vitro, which is dependent on the cofactor used. They can both hydrolyze a large range of low molecular weight compounds such as NAD+(H), FAD and ADPR, but NUDT6 is mainly active towards NADH, while NUDT9 displays a higher activity towards ADPR.


Stroke Prevention in Atrial Fibrillation: A Scientific Statement of JACC: Asia (Part 1).
Atrial fibrillation is the most common sustained cardiac arrhythmia and is associated with substantial increases in the risk of stroke and systemic thromboembolism. With the successful introduction of the first non-vitamin K antagonist direct oral anticoagulant (NOAC) in 2009, the role of vitamin K antagonists has been replaced in most clinical settings except in a few conditions when NOACs are contraindicated. Data for the use of NOACs in different clinical scenarios have been accumulating in the recent decade, and a more sophisticated strategy for atrial fibrillation patients is now warranted. JACC: Asia recently appointed a working group to summarize the most updated information regarding stroke prevention in AF. This statement aimed to provide possible treatment option in daily practice. Local availability, cost, and patient comorbidities should also be considered. Final decisions may still need to be individualized and based on clinicians' discretion. This is the part 1 of the whole statement.


Interfused semiconductor nanocrystals: brilliant blue photoluminescence and electroluminescence.
We describe a method for producing blue light-emitting interfused CdSe//ZnS (QE up to 60%) nanocrystals and report the good performance of an electroluminescent device which uses them (external quantum efficiency approximately 1.5 cd A(-1)).


What is the value of third-line chemotherapy in advanced gastroesophageal cancer? A 5-year retrospective analysis at a single center.
The survival benefit of using a non-cross resistant second-line chemotherapy in the third-line setting in metastatic gastroesophageal cancer is unproven. We evaluated the utility of third-line chemotherapy in patients treated at a single institution. Between 2010 and 2014, efficacy and toxicity data of patients who received three or more lines of systemic therapies for metastatic gastroesophageal adenocarcinoma at the National Cancer Centre Singapore was retrospectively analyzed. Thirty-two (6%) patients received three or more lines of chemotherapy. The median age and ECOG performance status were 59 years (36-82) and 1 (0-2), respectively. Majority of patients (88%) had tumor located in the stomach and 13 patients (41%) had diffuse histology or poorly cohesive or signet ring cells. Four (12%) patients had HER2-positive disease. Prior therapy was platinum (100%), fluoropyrimidine (97%), taxane (63%), irinotecan (28%), anthracycline (13%) and ramucirumab (3%). Third-line therapy consisted of 24 (75%) monotherapy, 6 (19%) doublet, 1 (3%) triplet chemotherapy and 1 (3%) clinical trial. Monotherapy irinotecan (44%) was most common, followed by docetaxel (19%) and paclitaxel (9%). Of 22 patients evaluable for response, there was 1 (5%) partial response, 9 (41%) stable disease. Median overall survival was 18.3 weeks (4.3-65.1). Of 30 patients evaluable for toxicities, 17 (57%) experienced at least one grade 3 or 4 toxicities. The benefit of using non-cross resistant second-line regimens as third-line chemotherapy was small with moderate toxicity. Newer agents such as nivolumab or TAS-102 or clinical trial may be preferred.


Severe influence of early pregnancy on newly reconstructed breast.
Since mastectomy may have a devastative effect on the patient's appearance, body image and psychology, especially in young women, immediate breast reconstruction is widely preferred to avoid the unpleasant results caused by the defect of mastectomy. Presented here is the case of a 33-year-old patient. Considering her fibrocystic mastopathy, atypical ductal hyperplasia and a history of familial breast cancer, subcutaneous mastectomy and breast reconstruction using an implant was planned with skin reduction and repositioning of the areola-nipple complex. During her postoperative follow-up examinations which were conducted periodically, it was expected that the formation of the breasts in relation to the prosthesis would take place in the healing time. In contrast, an increase in the skin thickness and breast fullness, massive filling in the submammary fold, a vertical suture depression and consolidation were observed. These unexpected deformities were based on a pregnancy beginning just after the last operation. Later, the breast findings were followed both clinically and photographically. After termination of the pregnancy, reduction in the skin thickness, involution of the glandular tissue and changes in the shape of the breasts were observed to continue for 6 months. The end result was the development of an unacceptable breast appearance which required a major revisional surgery. Early pregnancy after subcutaneous mastectomy with reconstruction severely affects development leading to distortions in the shape of the breast during pregnancy. Additionally, involution after delivery is not also good enough to provide acceptable outcomes.


Evolution of neuropsychological changes after partial callosotomy in intractable epilepsy.
Early neuropsychological changes following partial anterior callosotomy were evaluated in 15 patients with epilepsy (10 secondary generalized and 5 Lennox-Gastaut syndromes) by comparing their performances 1 month before surgery and then 15-20 and 90-100 days postoperatively without modifying the anticonvulsant treatment. The following neuropsychological and motor functions were tested: memory, attention, visuo-motor ability, posture, motor dexterity, language, praxis and gnosis. Social behaviour was also investigated. The main results are as follows: (i) most cognitive functions showed no significant variation; (ii) motor organization was still slightly impaired at the second check-up after the surgery; (iii) improvements in social behaviour and posture were frequently observed at the final evaluation. The analysis of individual cases highlights the influence of the extent of commissurotomy, lesions related to the surgical procedure and preoperative brain damage in determining the post-surgical profile. On this basis, the short-term neuropsychological cost of partial callosotomy appears to be low and seems to depend mostly on surgical parameters and brain conditions before the operation.


Topical Selenium Sulfide for the Treatment of Hyperkeratosis.
Hyperkeratosis presents as thickened skin. It can be congenital or acquired. Typically, it affects the palms and soles; the distribution of epidermal involvement is either diffuse, focal, or punctate. Microscopically, the pathologic signature of hyperkeratosis is marked orthokeratosis of the stratum corneum. Topical treatments provide the mainstay of therapy for hyperkeratosis. These include keratolytics (such as urea, salicylic acid, and lactic acid) and retinoids; physical debridement, topical corticosteroids, and phototherapy (using topical psoralen and ultraviolet A phototherapy) are other local therapeutic modalities. Selenium is a non-metallic essential element; its water-insoluble salt, selenium sulfide, is an active ingredient that is used (in either a foam, lotion, or shampoo) to treat not only seborrheic dermatitis but also tinea versicolor. Three individuals with hyperkeratosis involving their palms and/or soles are described; the hyperkeratosis was successful treated with topical selenium sulfide in either a 2.5% lotion/shampoo or a 2.75% foam. The response to topical selenium sulfide was not only rapid but also complete and sustained; none of the patients experienced any adverse events secondary to the therapy. In conclusion, we recommend that topical selenium sulfide be added to the therapeutic armamentarium for congenital or acquired hyperkeratosis-particularly for those patients with involvement of their palms and soles.


N-alpha-acetylation of Huntingtin protein increases its propensity to aggregate.
Huntington's disease (HD) is a neurodegenerative disorder caused by a poly-CAG expansion in the first exon of the HTT gene, resulting in an extended poly-glutamine tract in the N-terminal domain of the Huntingtin (Htt) protein product. Proteolytic fragments of the poly-glutamine-containing N-terminal domain form intranuclear aggregates that are correlated with HD. Post-translational modification of Htt has been shown to alter its function and aggregation properties. However, the effect of N-terminal Htt acetylation has not yet been considered. Here, we developed a bacterial system to produce unmodified or N-terminally acetylated and aggregation-inducible Htt protein. We used this system together with biochemical, biophysical, and imaging studies to confirm that the Htt N-terminus is an in vitro substrate for the NatA N-terminal acetyltransferase and show that N-terminal acetylation promotes aggregation. These studies represent the first link between N-terminal acetylation and the promotion of a neurodegenerative disease and implicates NatA-mediated Htt acetylation as a new potential therapeutic target in HD.


Discrepant Outcomes between National Kidney Transplant Data Registries in the United States.
Effects of reduced access to external data by transplant registries to improve accuracy and completeness of the collected data are compounded by different data management processes at three US organizations that maintain kidney transplant-related datasets. This analysis suggests that the datasets have large differences in reported outcomes that vary across different subsets of patients. These differences, along with recent disclosure of previously missing outcomes data, raise important questions about completeness of the outcome measures. Differences in recorded deaths seem to be increasing in recent years, reflecting the adverse effects of restricted access to external data sources. Although these registries are invaluable sources for the transplant community, discrepancies and incomplete reporting risk undermining their value for future analyses, particularly when used for developing national transplant policy or regulatory measures. Central to a transplant registry's quality are accuracy and completeness of the clinical information being captured, especially for important outcomes, such as graft failure or death. Effects of more limited access to external sources of death data for transplant registries are compounded by different data management processes at the United Network for Organ Sharing (UNOS), the Scientific Registry of Transplant Recipients (SRTR), and the United States Renal Data System (USRDS). This cross-sectional registry study examined differences in reported deaths among kidney transplant candidates and recipients of kidneys from deceased and living donors in 2000 through 2019 in three transplant datasets on the basis of data current as of 2020. We assessed annual death rates and survival estimates to visualize trends in reported deaths between sources. The UNOS dataset included 77,605 deaths among 315,346 recipients and 61,249 deaths among 275,000 nonpreemptively waitlisted candidates who were never transplanted. The SRTR dataset included 87,149 deaths among 315,152 recipients and 60,042 deaths among 259,584 waitlisted candidates. The USRDS dataset included 89,515 deaths among 311,955 candidates and 63,577 deaths among 238,167 waitlisted candidates. Annual death rates among the prevalent transplant population show accumulating differences across datasets-2.31%, 4.00%, and 4.03% by 2019 from UNOS, SRTR, and USRDS, respectively. Long-term survival outcomes were similar among nonpreemptively waitlisted candidates but showed more than 10% discordance between USRDS and UNOS among transplanted patients. Large differences in reported patient outcomes across datasets seem to be increasing, raising questions about their completeness. Understanding the differences between these datasets is essential for accurate, reliable interpretation of analyses that use these data for policy development, regulatory oversight, and research. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_10_24_JASN0000000000000194.mp3.


SUMO3 modification by PIAS1 modulates androgen receptor cellular distribution and stability.
Abnormal reactivation of androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) mainly results from overexpression and down-regulation of AR. Sumoylation of AR can influence its function. However, regulation of AR sumoylation by SUMO E3 ligases PIASs to modify AR distribution and stability are not well understood. We assessed the potential effect of SUMO3 modification on AR intracellular localization by immunostaining in AR-negative prostate cancer DU145 cells, and detected the effect of PIAS1/SUMO3 overexpression on AR sumoylation related degradation. Then we characterized AR sumoylation sites involved modified by SUMO3, and the key residue of PIAS1 involved in itself sumoylation and further mediated AR sumoylation (sumo3-conjugated), translocation and degradation. Finally we detected the recognition of PIAS1 (sumoylation ligase) to MDM2, a ubiquin ligase mediated AR degradation. We demonstrate that SUMO E3 ligase PIAS1, along with SUMO3, mediates AR cytosolic translocation and subsequent degradation via a ubiquitin-proteasome pathway. Although AR sumoylation occurs prior to ubiquitination, the SUMO-acceptor lysine 386 on AR, together with ubiquitin-acceptor lysine 845, contribute to PIAS1/SUMO3-induced AR nuclear export, ubiquitination and subsequent degradation. Moreover, PIAS1 itself is modified by SUMO3 overexpression, and mutation of SUMO-acceptor lysine 117 on PIAS1 can impair AR cytoplasmic distribution, demonstrating the essential role of sumoylated PIAS1 in AR translocation. We further determine that sumoylated PIAS1 interacts with AR lysine 386 and 845 to form a binary complex. Consistent with the effect on AR distribution, SUMO3 modification of PIAS1 is also required for AR ubiquitination and degradation by recruiting ubiquitin E3 ligase MDM2. Taken together, SUMO3 modification of PIAS1 modulates AR cellular distribution and stability. Our study provided the evidence the crosstalk between AR sumoylation and ubquitination mediated by PIAS1 and SUMO3.


[Chronic hemolysis and mitral insufficiency after surgical mitral valvuloplasty. Treatment by valve replacement, a case report].
The authors report a case featuring a chronic increase in lactic dehydrogenase (LHD) levels, 8 years after surgical mitral valvuloplasty with residual mitral regurgitation. This increase in LDH levels was the sign of chronic haemolysis and disappeared after valve replacement with a mechanical prosthesis. This rare complication was attributed to contact between the sutures and the teflon used for mitral valvuloplasty and turbulence created by the mitral regurgitation.


Connection between cardiac vascular permeability, myocardial edema, and inflammation during sepsis: role of the α1AMP-activated protein kinase isoform.
As adenosine monophosphate (AMP)-activated protein kinase both controls cytoskeleton organization in endothelial cells and exerts anti-inflammatory effects, we here postulated that it could influence vascular permeability and inflammation, thereby counteracting cardiac wall edema during sepsis. Controlled animal study. University research laboratory. C57BL/6J, α1AMPK, and α1AMPK mice. Sepsis was triggered in vivo using a sublethal injection of lipopolysaccharide (O55B5, 10 mg/kg), inducing systolic left ventricular dysfunction. Left ventricular function, edema, vascular permeability, and inflammation were assessed in vivo in both wild-type mice (α1AMPK) and α1AMP-activated protein kinase-deficient mice (α1AMPK). The 5-aminoimidazole-4-carboxamide riboside served to study the impact of AMP-activated protein kinase activation on vascular permeability in vivo. The integrity of endothelial cell monolayers was also examined in vitro after lipopolysaccharide challenge in the presence of aminoimidazole-4-carboxamide riboside and/or after α1AMP-activated protein kinase silencing. α1AMP-activated protein kinase deficiency dramatically impaired tolerance to lipopolysaccharide challenge. Indeed, α1AMPK exhibited heightened cardiac vascular permeability after lipopolysaccharide challenge compared with α1AMPK. Consequently, an increase in left ventricular mass corresponding to exaggerated wall edema occurred in α1AMPK, without any further decrease in systolic function. Mechanistically, the lipopolysaccharide-induced α1AMPK cardiac phenotype could not be attributed to major changes in the systemic inflammatory response but was due to an increased disruption of interendothelial tight junctions. Accordingly, AMP-activated protein kinase activation by aminoimidazole-4-carboxamide riboside counteracted lipopolysaccharide-induced hyperpermeability in wild-type mice in vivo as well as in endothelial cells in vitro. This effect was associated with a potent protection of zonula occludens-1 linear border pattern in endothelial cells. Our results demonstrate for the first time the involvement of a signaling pathway in the control of left ventricular wall edema during sepsis. AMP-activated protein kinase exerts a protective action through the preservation of interendothelial tight junctions. Interestingly, exaggerated left ventricular wall edema was not coupled with aggravated systolic dysfunction. However, it could contribute to diastolic dysfunction in patients with sepsis.


Pull through for Hirschsprung disease without planned rectal decompression is safe.
Definitive surgery for Hirschsprung disease (HD) is typically deferred to allow rectal washouts. In contrast, we have performed pull through on the next available operating list following diagnostic biopsy. Our aims are to compare outcomes of surgery without planned decompression vs. surgery where the timing of pull through was deferred. A consecutive series undergoing pull-through. Timing of surgery was at surgeon's discretion and classified as either no planned decompression surgery or other. Outcomes were i) complications graded >3b Clavien-Dindo (CD) within 30d, or ii) a need for a revisional pull through or iii) a post-pull-through stoma. We excluded total colonic aganglionosis. 156 children (116 boys) underwent pull-through. 71 had surgery without planned decompression. The indications for timing in the other 85 were: planned after home washouts (n = 28), planned after stoma (n = 29), diagnostic error (n = 19), prematurity (n = 3), late presentation (n = 2) and other (n = 4). The mean age at surgery in the surgery without planned decompression group was 18 days (range 1-49 days) vs. 310 days (range 14-4084 days). 5/72 (7%) undergoing surgery without planned decompression experienced a complication of ≥CD 3b, compared to 7/85 (8%) of delayed surgery (p = 0.8). 3/71 (4%) of the surgery without planned decompression group required a stoma following pull through compared to 11/83 (13%) of the delayed group (p = 0.059). 5/71 (7%) of the surgery without planned decompression group required revisional pull through compared to 13/85 (15%) of the delayed surgery group (p = 0.1). Surgery without planned rectal decompression for HD leads to no increase in significant complications, requirement for stoma or revision. Early definitive surgery is safe, and the use of pre-operative stoma or rectal washouts is not always necessary. III.


The physical assessment of the patient with arterial disease.
Utilizing techniques of inspection, palpation, and auscultation the complete arterial system of a patient should be examined when arterial insufficiency is suspected. Examination of pulses of the upper part of the body is important not only in localizing disease but also in indicating diffuse disease. Although described separatley in this article, the examination of the arterial system can be integrated in a complete physical examination when the examiner is assessing the extremities, the abdomen, and the cardiovascular system.


An overview of sexual harassment.
A few widely publicized cases have made sexual harassment a salient subject in the 1990s. This article reviews the topic in a comprehensive manner, with particular attention to demographic information, psychosocial consequences, appropriate therapeutic interventions, and related psychological issues. Computerized literature searches were used to identify research and review papers from psychiatry and psychology journals. Nonscientific works that provide additional information are also cited. The literature suggests that sexual harassment is a widespread phenomenon, affecting 42% of women and 15% of men in occupational settings, 73% of women and 22% of men during medical training, and lower percentages in other educational settings. Despite the pervasive nature of this problem, only 1%-7% of victims file formal complaints. Sexual harassment produces an array of psychological and physical symptoms in over 90% of victims, and 12% seek help from mental health care professionals. Self-doubt is a central issue regardless of gender, but in instances where the perpetrator is male and the victim is female, there are ramifications unique to the trauma of gender-based abuse. It is critical that therapists avoid contributing to the process of "second injury" and not imply that patients have brought their troubles on themselves. Key therapeutic tasks include empathy, validation, and empowerment. Few experimental studies have focused on the victims of sexual harassment, and none have focused on the perpetrators. Psychiatry can play an invaluable role in the assessment and treatment of victims, the fostering of education and research in this area, and the understanding of underlying psychological and gender issues.


Response time of mitochondrial oxygen consumption following stepwise changes in cardiac energy demand.
We determined the speed with which mitochondrial oxygen consumption and therefore the mitochondrial ATP-synthesis adapted to changes in metabolic demand in the rabbit heart. This was done by measuring the oxygen uptake of the whole heart during a stepwise change in heart rate and correcting for the time taken by diffusion and by convective transport in the blood vessels. Data for the correction for transport time were obtained from the response of venous oxygen concentration to a stepwise change of arterial oxygen concentration. The time constant of the response of mitochondrial oxygen consumption to a step change in heart rate was found to be 4-8 s.


Reduced nocturnal blood pressure dip and sustained nighttime hypertension are specific markers of secondary hypertension.
To investigate with the use of ambulatory blood pressure (BP) monitoring whether nocturnal BP dip and nighttime BP values are different in children with untreated primary and secondary hypertension. Ambulatory BP monitoring studies from 145 children with untreated hypertension were retrospectively analyzed. Forty-five children had primary hypertension and 100 children had secondary hypertension. Children with secondary hypertension had lower nocturnal BP dip for systolic and diastolic BP in comparison to children with primary hypertension (8% +/- 5% vs 14% +/- 4% for systolic and 14% +/- 7% vs 22% +/- 5% for diastolic BP, P < .0001 for both). Eleven percent of children with primary hypertension were classified as nondipper (BP dip <10%) for systolic BP and no child for diastolic BP; on the contrary, in children with secondary hypertension, 65% were nondippers for systolic and 21% for diastolic BP. Nocturnal systolic and diastolic BP loads were significantly greater in children with secondary hypertension than in those with primary hypertension. Reduced nocturnal BP dip and sustained nighttime BP elevation are specific markers of secondary hypertension in children with untreated hypertension. Children with blunted nocturnal BP dip or sustained nighttime hypertension should be thoroughly investigated searching for the underlying cause of hypertension.


Reversible inhibition of the in vitro coagulation of human plasma by lectins.
Wheat germ agglutinin (WGA) and concanavalin A (Con-A) (also red kidney bean agglutinin, PHA) have been found to be inhibitors of plasma clotting in vitro. At 40 micrograms/ml and 250 micrograms/ml (4.4 MicroM and 10 microM in carbohydrate binding sites, final concentrations) respectively, WGA and Con-A are able to double the activated partial thromboplastin time of normal human control plasma. Their inhibitory effect is due to their capacity to interact with the carbohydrate portion of blood clotting factors. It is totally abolished in the presence of specific saccharides for WGA or Con-A and is attenuated in the presence of 4% (v/v, final concentration) of human erythrocytes. The action of WGA is mediated by its ability to interact with N-acetylneuraminic acid. When purified phospholipid vesicles plus kaolin are used as an activator instead of cephalidin, this effect persists to the same extent. These two lectins also prolong the plasma clotting time using Russell's viper venom plus purified phospholipid vesicles as an activator. Quick's time was also prolonged by WGA and Con-A but to a lesser extent in this case. WGA can interact directly with some purified blood clotting factors (IX, X and II) in a classical lectin-glycoprotein precipitin reaction. When assessed at individual factors level in whole plasma using clogging assays, direct inhibitions by WGA are only apparent.


Leptomeningeal involvement by epithelial ovarian carcinoma: a case report.
A patient with epithelial ovarian carcinoma, who developed meningeal carcinomatosis, is hereby presented. A review of the literature revealed that only a few cases of this entity have been reported. With the prolonged survival of ovarian cancer patients treated by combination chemotherapy, it is expected that meningeal involvement will be found more often.


Prospective evaluation of selective criteria for imaging among children with suspected blunt renal trauma.
The evaluation of children with suspected blunt renal injury relies mainly on clinical assessment, urinalysis, and imaging studies. Because imaging studies rarely influence management, yet entail both risk and expense, we investigated a protocol to define their appropriate use. During a one-year period, children seen in the emergency department underwent a mandated radiographic evaluation for renal injury only if they had (a) severe injuries or (b) a urinalysis with greater than 20 RBC/hpf. Thirty-two children were enrolled; 16 had imaging studies that detected four abnormalities, ie, three contusions and one incidental finding of renal papillary necrosis. All children with abnormal imaging studies had greater than 20 RBC on urinalysis. None of the 16 children who were not studied radiographically developed complications related to renal trauma during short-term follow-up. Our findings support earlier recommendations for limiting the use of imaging for suspected blunt renal trauma in children with minor to moderate injuries and hematuria of less than or equal to 20 RBC/hpf.


Outcomes and survival rates of childhood osteosarcoma in Iran, A report from MAHAK Pediatric Cancer Treatment and Research Center, from 2007 to 2020.
Osteosarcoma is one of the most common childhood bone malignancies. Although chemotherapy protocol including methotrexate is an effective treatment for osteosarcoma, some other regimens have excluded it because of its complications. This retrospective study was conducted on 93 children younger than 15 years old who were diagnosed with osteosarcomafrom March 2007 to January 2020. Two chemotherapy protocols were administrated for patients, namely, DCM protocol (Doxorubicin-Cisplatin-Methotrexate) and German protocol (excluding methotrexate). All statistical analysis was conducted using SPSS-25 software. Among patients, 47.31% were male. Patients' age ranged from 3 to 15 with the mean of 10.41 ± 0.32 years. Femur was the most frequent primary tumor site (59.14%), followed by tibia (22.58%). Metastasis rate at diagnosis was 17.20% in our study. Furthermore, the 5-year overall survival (OS) of total patients was 37.3 ± 7.5%, whereas the 5-year OS of males and females was 33.6 ± 10.9% and 39.8 ± 10.6%, respectively. The 5-year OS of methotrexate regimen was 15.6 ± 9.6%, whereas that of methotrexate-free protocol was 50.2 ± 9.0%. Female patients had better survival rates than males. In addition, the chemotherapy protocol excluding methotrexate significantly increased the overall and event free survival of patients.


Significant Prognostic Factors Influencing the Survival Difference of Oral Tongue Squamous Cell Carcinoma.
Oral tongue squamous cell carcinoma is the most common malignancy in the oral cavity. Overall survival varies across many countries, and poor prognosis is prevalent in developing countries, including Thailand. Our study aimed to identify prognostic factors that affected survival for oral tongue cancer in Thailand. We performed a retrospective study of 183 patients diagnosed with oral tongue squamous cell carcinoma between January 2012 and December 2016 and who underwent multidisciplinary treatment. The disease stage was classified by tumor-nodes-metastasis (TNM) staging system. The survival outcome was calculated and represented in median survival time. Univariate and multivariate Cox proportional hazards models were used to identify factors that impacted survival outcomes. A clear margin was achieved in 88.8% of the 125 operated patients. Radiotherapy was given to 115 patients (62.84%). The survival shown in Kaplan-Meier curves was significantly lower according to advanced TNM stage, poor histologic grade, nonsurgical treatment, and patients treated with radical neck dissection. Radiotherapy was a good prognostic factor [hazard ratio (HR) 0.25, P = 0.022]. Poor prognostic factors were body mass index less than 18.5 kg per m2 (HR 3.03), vertical tumor dimension 20 mm or more (HR 5.84), non-well-differentiated grade tumor (HR 3.09), and operated cases with radical neck dissection (HR 4.29). Surgical treatment can improve the survival outcome, whereas advanced stage and poor histological grading can worsen the overall survival. For oral tongue squamous cell carcinoma, radiotherapy was a good prognostic factor. On the contrary, a tumor with large vertical size, closed surgical margin, poor histologic grade, and radical neck dissection in the operated group were poor prognostic factors.


Experience in diagnosis and treatment of impotence caused by cavernosal leak syndrome.
To delineate neural, arterial, and venous components contributing to impotence, we used a previously described noninvasive screening sequence combined with stimulation of artificial erection with papaverine injection, selective pudendal arteriography (SPA), and dynamic cavernosography (DC). Among 572 men with impotence, age range 17 to 78 years (average age 54.8 years), 26 men with potential cavernosal leaks in absence of other factors were identified; 16 underwent DC; among these five had normal cavernous venous drainage. Eight men with abnormal cavernosal venous drainage required cavernous infusion flow rates higher than 120 ml/min to obtain erection and higher than 40 ml/min to maintain erection. Radiographic studies showed cavernosal leakage in all eight patients. Eight men, ages 39 to 61 years, underwent surgical ablation of abnormal cavernosal venous drainage. Among these, five men have had excellent results for up to 3 years. One failure was related to unrecognized penile arterial disease later shown by SPA. In two men small doses of papaverine now induce erection. We now recommend SPA before DC to rule out an arterial abnormality. Accurate identification of factors contributing to erectile failure is critical for successful treatment; in this experience candidates for correction of cavernosal leak syndrome were uncommon.


The effect of corona discharge on Der p 1.
Reduction of house dust mite allergens in the domestic environment can play an important part in reducing sensitization and in the amelioration of symptoms in atopic individuals. Chemical and physical methods have been tried with varied levels of success. The present paper presents a novel electrostatic way of destroying Der p 1, the major mite allergen. To assess the efficacy of negative Trichel, negative continuous glow, positive pulse and positive continuous glow corona in destroying Der p 1. To determine whether ozone has any effect on the integrity of Der p 1 in the experimental conditions present. A simple point-to-plane apparatus was used to irradiate samples of Der p 1 for periods of 1, 15, 30, 45, 60, 120, 180, 240 and 300 min. Controls were exposed to the atmosphere with no corona products present for the equivalent time. The effect of the corona by-product ozone was investigated alone by exposing samples of Der p 1 to molecular ozone for 60 min. Der p 1 concentration was quantified by two-site monoclonal antibody ELISA. High current negative glow resulted in a 67.37% reduction in Der p 1 concentration after 300 min compared with a 50.5% reduction from a low current Trichel regime. High current positive glow corona gave a reduction of 25.22% while a low current positive pulse corona caused a 13.72% reduction after 300 min. All these reductions were statistically significant (P < 0.05) compared with unexposed controls. Negative corona always gave greater percentage reductions in Der p 1 concentration for each time exposure investigated. The pattern of percentage reduction follows an exponential rise to maximum relationship in respect to time. Samples of Der p 1 were not affected by exposure to molecular ozone. These data indicate corona products to be a powerful new method of destroying Der p 1 allergen that is not dependent on the presence of the oxidizing corona product ozone.


Proton tunneling in the A∙T Watson-Crick DNA base pair: myth or reality?
The results and conclusions reached by Godbeer et al. in their recent work, that proton tunneling in the A∙T(WC) Watson-Crick (WC) DNA base pair occurs according to the Löwdin's (L) model, but with a small (~10(-9)) probability were critically analyzed. Here, it was shown that this finding overestimates the possibility of the proton tunneling at the A∙T(WC)↔A*∙T*(L) tautomerization, because this process cannot be implemented as a chemical reaction. Furthermore, it was outlined those biologically important nucleobase mispairs (A∙A*↔A*∙A, G∙G*↔G*∙G, T∙T*↔T*∙T, C∙C*↔C*∙C, H∙H*↔H*∙H (H - hypoxanthine)) - the players in the field of the spontaneous point mutagenesis - where the tunneling of protons is expected and for which the application of the model proposed by Godbeer et al. can be productive.


Changes in the lymphoreticular system of Swiss mice subjected to antigenic stimulation, immunosuppression, or both.
The influence of chronic antigenic stimulation, immunosuppression with azathioprine, or both acting simultaneously on the lymphoreticular system in Swiss mice was studied. The response consisted of abnormal hyperplasia of the lymphoreticular system with the character of malignant lymphoma. On the basis of the microscopic pattern of the changes, three types were distinguished. Chronic immunization by humoral-cellular dysregulation, can cause abnormal hyperplasia of the lymphatic system.


Men and women affected by Sars-CoV-2 pneumonia: same CT features but different outcome.
To compare the computed tomography (CT) features of Sars-CoV-2 pneumonia between the two sexes and among different age groups. Consecutive patients (n=331) who presented to the emergency department and underwent chest CT and reverse transcription polymerase chain reaction (RT-PCR) with a time interval <7 days, which were subsequently found to be consistent with Sars-CoV-2 infection, were enrolled retrospectively. Two experienced radiologists evaluated the images in consensus, recording the number of pulmonary lobes with ground-glass opacities and with consolidation. A CT score was subsequently calculated based on the percentage involvement of each lobe. Clinical symptoms, comorbidities, and level of required hospitalisation were noted. In-hospital mortality was recorded and analysed via the Kaplan-Meier estimator. Males and females had the same age distribution. No statistically significant difference was found in the analysed CT features and in the CT score (p=0.31) between the sexes. More females were affected by two or more comorbidities (17.1% versus 7.5%, p=0.024), all comorbidities except diabetes were more prevalent in females. Women had a higher probability to be discharged home and a lower probability to be admitted to the intensive care unit (ICU; p=0.008), in-hospital mortality was inferior (13.5% versus 22%). Despite more comorbidities, women had lower hospital admission and mortality, which was independent of CT findings between both sexes.


Stapling techniques for easy construction of an ileal J-pouch.
A technique for the extended use of GIA and EEA or ILS staplers in the easy construction of an ileal J-pouch and mucosal proctectomy has been described herein. The technique for construction of the J-pouch involves the almost exclusive multiple use of a GIA stapling device. The described mucosal proctectomy techniques use the EEA stapler for good traction and visualization for everted electrocautery suction mucosal dissection. With the use of these techniques, the integrity of the patient's tissue is preserved, suture lines are stronger, and the operating time is greatly reduced.


Vasovagal reactions in blood donors during or immediately after blood donation.
The aim of the study was to estimate the type, incidence and causes of donor adverse reactions during and after blood donation in a Greek Blood Bank, where medical staff is responsible for donor selection. 12 173 blood donors were studied for adverse reactions. One-hundred and seven (0.87%) donors had a vasovagal reaction during or after blood donation. Donors who gave blood occasionally had a significant greater incidence of reactions compared with volunteer donors (1.15 versus 0.53%) (P < 0.001). There was no significant difference between men and women (0.85 versus 0.95%). First-time donors (1.7 versus 0.68%) and those under 30 years (1.15 versus 0.71%] had a significant greater possibility to have a reaction (P < 0.001). Twenty-two of 107 (20.5%) donors had a syncopal reaction. There was not a causative correlation of haematocrit, haemoglobin, systolic and diastolic blood pressure, pulse rate and weight in women (except weight in men) in developing a reaction. The stressing experience of phlebotomy was the reason for the higher frequency of a reaction. The incidence of reactions in our donors is lower than in other studies, and the possible reason for this is that only physicians are responsible for the selection of donors and trained personnel are careful of them during the donation process.


Continuous in situ cold perfusion with histidine tryptophan ketoglutarate solution in nephron sparing surgery for renal tumors.
In transplantation medicine the superiority of Bretschneider's histidine tryptophan ketoglutarate solution has been demonstrated in various animal investigations and in donor organs under clinical conditions. Because of the wide use of ultrasound scans and computerized tomography there has been a sharp increase in the number of small renal tumors detected. Therefore, efficient protection methods designed to conserve kidney tissues are attracting growing attention. We report on 11 patients with space-occupying lesions involving a solitary kidney. All tumor resections were performed under continuous in situ perfusion with Bretschneider's solution. Even when dealing with extensive tumors involving the hilum, complete resection and reconstruction of the kidney in situ proved feasible. The mean cold ischemia time was 62.1 minutes (range 18 to 88) and mean Bretschneider's perfusion volume was 2,875 cc. The kidneys resumed excretion within an average of 16.8 minutes (range 0 to 60) and no patient required dialysis. Apart from temporary elevation of serum creatinine levels, postoperative renal function was unimpaired. There were no changes in serum electrolyte levels and no disorders of cardiac conduction. One kidney was lost postoperatively due to renal artery embolism. Continuous in situ perfusion with Bretschneider's solution is a new and interesting method for patients undergoing partial nephrectomy. Particularly for locally extended tumors, this procedure is highly efficient for intrarenal surgery.


Oviposition by Plagiodera versicolora on Salix matsudana cv. 'Zhuliu' alters the leaf transcriptome and impairs larval performance.
Insect egg deposition can induce plant defenses against their larvae. Previous studies have primarily focused on herbaceous plant defenses; however, little is known about how the Salicaceae respond to insect egg deposition and defend themselves against herbivores. By combining plant defense gene studies and bioassays, we investigated the effect of the coleoptera Plagiodera versicolora egg deposition on willow (Salix matsudana cv. 'Zhuliu') and examined the interactions at the plant resistance and transcriptome levels. RNA-seq data were utilized to analyze changes in the leaf transcriptome with and without oviposition, and also the changes in the leaf transcriptome of feeding-damaged leaves with and without prior oviposition. P. versicolora oviposition on willow leaves resulted in altered expression levels of transcripts associated with plant stress and metabolic responses. Compared with leaves with no oviposition, leaves with egg deposition showed a slight increase in phenylpropanoid biosynthesis and phytohormone signaling genes after larval feeding. The RNA-seq analysis revealed alterations in willow transcripts in response to leaf beetle infestations. Bioassays indicated that oviposition by P. versicolora on willows reduced subsequent larvae performance, suggesting that prior oviposition by P. versicolora could increase willows' resistance to larvae. This study advances our knowledge of how oviposition by coleoptera insects induces changes in the resistance of leaves to herbivory in the Salicaceae family.


Cation transport and membrane potential properties of primary astroglial cultures from neonatal rat brains.
This paper describes K+ and Na+ content and transport in primary monolayer cultures from dissociated newborn rat brains, considered to consist predominantly of astroglial cells. Net changes in cation content after addition of ouabain, and steady state fluxes using 86Rb+ as a marker for K+ and 22Na+ as a marker for Na+, were measured. The results found indicate that the cells maintained a conventional pattern of cation homeostasis with net efflux of K+ being balanced by its active uptake and net uptake of Na+ balanced by active extrusion mediated by a ouabain sensitive (Na+K) pump. These processes maintained internal measured K+:Na+ ratios of 12--25:1. The cells were normally flat but addition of DBcAMP caused them to round up and form numerous processes, an appearance resembling that of astroglial cells in vivo. DBcAMP treatment also reduced the steady state levels of K+ measured with 86Rb+ by 15--30%, and had no effect on initial rates of 86Rb+ and 22Na+ uptake. The membrane potentials of cells treated with DBcAMP were studied, since only these were easily impaled. The membrane potentials of separate groups of cells gave means ranging from --65 to --75 mV at 35 degrees C, at an external K+ concentration ([K+]o) of 4.5 mM. The dependence of the membrane potentials of individual cells and groups of cells on [K+]o was studied. The slope of the potential per 10-fold change in [K+]o was 55--57 mV, at concentrations of K+ greater than 10--20 mM K+, and diverged from this slope at concentrations below this. This shows that these cells had some permeability to ions other than K+. Assuming that Na+ was the only other ion affecting the membrane potential, it was calculated that the permeability to Na+ was about 30 times less than K+. A similar result was obtained based on estimates of Na+ and K+ permeability from transport experiments on cells also treated with DBcAMP. The results obtained from these cells are compared to those found for other cultured glial cells and glial cells in vivo. We conclude that the membrane potentials of the cultured cells used in the present study show the closest resemblance so far to glia in vivo, since they are large and negative and are determined mainly by K+. However, the cultured cells have different properties from those reported in some studies for glial cells in vivo by showing free permeability to ions other than K+.


Peptide-directed self-assembly of hydrogels.
This review focuses on the self-assembly of macromolecules mediated by the biorecognition of peptide/protein domains. Structures forming alpha-helices and beta-sheets have been used to mediate self-assembly into hydrogels of peptides, reactive copolymers and peptide motifs, block copolymers, and graft copolymers. Structural factors governing the self-assembly of these molecules into precisely defined three-dimensional structures (hydrogels) are reviewed. The incorporation of peptide motifs into hybrid systems, composed of synthetic and natural macromolecules, enhances design opportunities for new biomaterials when compared to individual components.


Quantum Chemistry on Graphical Processing Units. 1. Strategies for Two-Electron Integral Evaluation.
Modern videogames place increasing demands on the computational and graphical hardware, leading to novel architectures that have great potential in the context of high performance computing and molecular simulation. We demonstrate that Graphical Processing Units (GPUs) can be used very efficiently to calculate two-electron repulsion integrals over Gaussian basis functions [Formula: see text] the first step in most quantum chemistry calculations. A benchmark test performed for the evaluation of approximately 10(6) (ss|ss) integrals over contracted s-orbitals showed that a naïve algorithm implemented on the GPU achieves up to 130-fold speedup over a traditional CPU implementation on an AMD Opteron. Subsequent calculations of the Coulomb operator for a 256-atom DNA strand show that the GPU advantage is maintained for basis sets including higher angular momentum functions.


The crosstalk between LINC01089 and hippo pathway inhibits osteosarcoma progression.
Osteosarcoma is the most common malignancy in children, with high morbidity worldwide. Researches indicated that long non-coding RNAs (lncRNAs) played crucial roles in various cancers. Nevertheless, study investigating lncRNA long intergenic non-protein coding RNA 1089 (LINC01089) in osteosarcoma is extremely rare. Thus, the research of LINC01089 is of great significance. qRT-PCR and western blot were done to test the expression of RNAs and proteins in osteosarcoma cells. Functional assays were carried out to evaluate biological behaviors of hFOB1.19 and osteosarcoma cells with or without LINC01089 knockdown and overexpression. In vitro and in vivo experiments in a rescue manner were performed to reveal the influences of LINC01089 and Hippo pathway on osteosarcoma cell phenotype and tumor growth. LINC01089 was down-regulated in osteosarcoma cells and overexpressing LINC01089 was validated to restrain cell growth in vitro and tumor growth in vivo. Additionally, silencing LINC01089 could exacerbate cell malignant behaviors. Correlation of LINC01089 and Hippo pathway was proved. Overexpressing LINC01089 could activate Hippo pathway to exert antitumor effects. LINC01089 could restrain the progression of osteosarcoma through activating Hippo pathway.


Isolation and characterization of Enterobacter cloacae capable of metabolizing asparagine.
A gram-negative, rod-shaped bacterium capable of utilizing L-asparagine as its sole source of carbon and nitrogen was isolated from soil and identified as Enterobacter cloacae. An intracellularly expressed L-asparaginase was detected and it deaminated L-asparagine to aspartic acid and ammonia. High-pressure liquid chromatography analysis of a cell-free asparaginase reaction mixture indicated that 2.8 mM L-asparagine was hydrolyzed to 2.2 and 2.8 mM aspartic acid and ammonia, respectively, within 20 min of incubation. High asparaginase activity was found in cells cultured on L-fructose, D-galactose, saccharose, or maltose, and in cells cultured on L-asparagine as the sole nitrogen source. The pH and temperature optimum of L-asparaginase was 8.5 and 37-42 degrees C, respectively. The half-life of the enzyme at 30 degrees C and 37 degrees C was 10 and 8 h, respectively.


Rationale and design of the Early Sleeve gastrectomy In New Onset Diabetic Obese Patients (ESINODOP) trial.
No randomized clinical trials (RCTs) have yet evaluated the bariatric surgery's efficacy and safety in patients newly diagnosed with type 2 diabetes mellitus (T2DM). The aim of this multicenter RCT is to compare bariatric surgery, particularly laparoscopic sleeve gastrectomy (LSG), with conventional medical therapy (CMT) in obese patients (body mass index between 30 and 42 kg/m2) newly diagnosed with T2DM and without any diabetes-related complications at any stage. A total of 100 eligible patients will be randomized at a 1:1 ratio to undergo one of the two planned treatments and will be followed for at least 6 years after randomization. The main objective of the ESINODOP trial is to investigate the efficacy of LSG compared with CMT alone in inducing and maintaining a remission of T2DM (defined as HbA1c levels ≤6.0 %, without active pharmacologic therapy after 1 year). The remission of T2DM will also be evaluated with the criteria provided by the American Diabetes Association (ADA), and the additional parameters such as adverse event rates, micro- and macrovascular complications, weight loss, gastrointestinal hormones, and quality of life will be compared. The study started on September 2015 and the planned recruitment period is 3 years. Patient recruitment and follow-up take place in the two diabetology and nutrition centers participating in the study, which are performed on a national basis. The ESINODOP trial is designed with the intent of comparing the efficacy of CMT alone to that of CMT in conjunction with LSG performed at the time of diabetes diagnosis in mildly obese diabetic patients. Currently, patients with these characteristics are not eligible for bariatric/metabolic surgery.


Medium-term survival after primary angioplasty for myocardial infarction complicated by cardiogenic shock after the age of 75 years.
To assess mortality in people > or =75 years of age 6 months after myocardial infarction complicated by cardiogenic shock and treated by angioplasty with complete revascularisation and optimal anti-thrombotic treatment; to compare results to those of younger patients with or without shock and to analyse predictive factors for death. The study is based on 1011 consecutive patients with myocardial infarction admitted for primary angioplasty, subdivided into four groups by age and the presence or absence of cardiogenic shock: group 1 (<75 years of age without shock, n=733), group 2 (<75 years of age with shock, n=49), group 3 (> or =75 years of age without shock, n=208) and group 4 (> or =75 years of age with shock, n=20). These four patient groups were compared for mortality rates and predictive factors for in-hospital and 6 month mortality. In-hospital mortality in groups 1 to 4 was 1.7%, 30.6%, 9.1%, and 70% (p<0.0001) respectively and 6-month mortality was 3.1%, 40%, 16% and 78% (P<0.0001). By univariate analysis renal failure was a predictive factor for death at 6 months in patients without cardiogenic shock (groups 1 and 3), and left ventricular function in patients in group 2. No predictive factors were found in group 4 patients. The independent predictive factors for death at 6 months were: age >75 years of age (P<0.0003), cardiogenic shock (P<0.0001), triple vessel lesions (P<0.01) and creatinine clearance (P=0.004). Mortality after angioplasty remains high in people > or =75 years with cardiogenic shock despite all the advances in the management of myocardial infarction. These disappointing results should encourage us to assess the role of surgical revascularisation and circulatory assistance.


Combination of Amoxicillin 3000 mg and Probenecid Versus 1500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients With Human Immunodeficiency Virus: An Open-Label, Randomized, Controlled, Non-Inferiority Trial.
Amoxicillin plus probenecid is an alternative to intramuscular benzathine penicillin G for treating syphilis in the United Kingdom. Low-dose amoxicillin is an alternative treatment option used in Japan. We conducted an open-label, randomized, controlled, non-inferiority trial between 31 August 2018, and 3 February 2022, to compare 1500 mg low-dose amoxicillin monotherapy with the combination of 3000 mg amoxicillin and probenecid (non-inferiority margin 10%). Patients with human immunodeficiency virus (HIV) infection and syphilis were eligible. The primary outcome was the cumulative serological cure rate within 12 months post-treatment, measured using the manual rapid plasma reagin card test. Secondary outcomes included safety assessment. A total of 112 participants were randomized into 2 groups. Serological cure rates within 12 months were 90.6% and 94.4% with the low-dose amoxicillin and combination regimens, respectively. Serological cure rates for early syphilis within 12 months were 93.5% and 97.9% with the low-dose amoxicillin and combination regimens, respectively. Non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid overall and for early syphilis was not confirmed. No significant side effects were detected. This is the first randomized controlled trial to demonstrate a high efficacy of amoxicillin-based regimens for treating syphilis in patients with HIV infection, and the non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid was not seen. Therefore, amoxicillin monotherapy could be a good alternative to intramuscular benzathine penicillin G with fewer side effects. However, further studies comparing with benzathine penicillin G in different populations and with larger sample sizes are needed. (UMIN000033986).


Impact of hot temperatures on death in London: a time series approach.
This study investigated the relation between heat and mortality in London to determine the temperature threshold at which death rates increase and to quantify the effect of extreme temperatures on mortality. Daily data on all cause mortality and temperature were obtained for a 21 year period and the relation between them investigated both graphically and by using non-parametric time series methods of analysis. Greater London. Daily mortality counts in Greater London between January 1976 and December 1996. A plot of the basic mortality-temperature relation suggested that a rise in heat related deaths began at about 19 degrees C. Average temperatures above the 97th centile value of 21.5 degrees C (excluding those days from a 15 day "heatwave" period in 1976) resulted in an increase in deaths of 3.34% (95% CI 2.47% to 4.23%) for every one degree increase in average temperature above this value. It was found that the 1976 heatwave resulted in a particularly large number of deaths in comparison with other hot periods. These results suggest that heat related deaths in London may begin at relatively low temperatures. Hot days occurring in the early part of any year may have a larger effect than those occurring later on; and analysis of separate heatwave periods suggest that episodes of long duration and of highest temperature have the largest mortality effect.


Staging laparoscopy in gastric cancer surgery. A population-based cohort study in patients undergoing gastrectomy with curative intent.
Studies on the value of a staging laparoscopy in detecting metastases in gastric cancer patients show great variation. This study investigates the avoidable surgery rate in patients with and without a staging laparoscopy scheduled for surgery with curative intent. This population-based cohort study included all patients with an intentional resection for a potentially curable gastric adenocarcinoma, between 2011 and 2016, registered in the Dutch Upper GI Cancer audit. Patients with and without a staging laparoscopy were compared. The primary outcome was the avoidable surgery rate (detection of metastases and/or locoregional non-resectable tumor during intentional gastrectomy). Secondary outcomes were the negative predictive value, postoperative morbidity and pathology parameters. 2849 patients who underwent an intentional gastrectomy were included. 414 of 2849 (14.5%) patients underwent a staging laparoscopy before initiation of treatment. The avoidable surgery rate was 16.2% in the staging laparoscopy group, compared to 8.5% in the non-staging group (P < 0.001), resulting in a negative predictive value of 83.8%. The avoidable surgery rate remained significantly different after correction for possible confounders. The main reason for not executing the gastrectomy was the presence of distant metastasis in both groups. cT and cN stage were significantly higher in patients who underwent a staging laparoscopy. The staging laparoscopy group had a higher cTN and pTN stage, implicating selection of patients with more advanced disease for a staging laparoscopy. Despite the staging laparoscopy, a higher rate of avoidable surgery was found, suggesting a low sensitivity for detecting metastases or locoregional non-resectability in this patient group.


Integrated Treatment at the First Stage: Increasing Motivation for Alcohol Patients with Comorbid Disorders during Inpatient Detoxification.
Co-occurring mental disorders can complicate the detoxification treatment process and outcome. The aim of this study is to examine whether a brief psychoeducational group counseling session during detoxification treatment can increase the motivation for and utilization of subsequent treatments. Interventions increased utilization of post-detoxification treatment and reduced alcohol-related readmissions. Higher depression or trauma scores were associated with higher rates of utilization of treatment. Patients received either a brief manualised group intervention on the interrelation of alcohol use disorder (AUD) and major depression (MD) or AUD and post-traumatic stress disorder (PTSD) or a cognitive training session (control group). Of the 784 patients treated in the study period, 171 participants were quasi-randomly allocated to groups. Self-reported motivation was measured before and after intervention, transition into AUD treatment and readmissions were collected after detoxification treatment. Participating in any of the intervention groups increased the utilization of AUD treatment after inpatient detoxification (χ2 = 6.15, P = 0.02) and decreased readmissions 6 months after discharge (χ2 = 7.46, P = 0.01). Depression and trauma scores moderated the effect: associations with the utilization of post-detoxification treatment were found in participants with higher depression (OR = 5.84, 95% CI = 1.17-29.04) or trauma scores (OR = 10.17, 95% CI = 1.54-67.1). An integrated intervention approach for dual diagnosis at the beginning of the treatment can increase motivation for continued AUD treatment. Especially affected dual diagnosis patients can benefit from this treatment.


Breeding site fidelity in willow ptarmigan: the influence of previous reproductive success and familiarity with partner and territory.
Breeding site fidelity is high in willow ptarmigan: only 9% of males and 31% of females switched territories between years. Unpaired males were more likely to switch territories than paired males. For paired males, survival of their previous partner and reproductive success in year x did not influence probability of switching in year x+1. A female was more likely to switch territories if her previous partner disappeared. If her partner returned, she had a higher probability of switching if she did not produce chicks the previous year. Most hens moved to the territories of older males, although hens paired with unfamiliar older males did not have higher reproductive success than those paired with yearlings. Individuals that paired with their previous partner laid earlier and produced heavier chicks than those paired with unfamiliar partners. Excluding birds paired with familiar partners, survival and reproductive success in year x+1 was similar for males and females that did or did not switch territories. Males had a higher probability of producing chicks after switching than before, but females were more likely to lose their clutch after switching. For both sexes, birds that switched territories were as successful as the birds that replaced them on their former territories. We conclude that high site fidelity in willow ptarmigan is maintained because of the benefits of pairing with a familiar partner.


Spironolactone in Dermatology: Uses in Acne, Hidradenitis Suppurativa, Female Pattern Baldness, and Hirsutism.
Spironolactone is an economical potassium-sparing diuretic with an anti-androgenic effect and a good safety profile. Our experience suggests that this diuretic is underexploited in dermatology even though there is evidence supporting its use in several skin conditions. When prescribed for acne in female patients (level 1-2 evidence; strength of recommendation, B), for example, it can reduce the need for antibiotics and possibly isotretinoin. Other diseases in which spironolactone is potentially useful are hidradenitis suppurativa and female androgenetic alopecia. We discuss the indications for spironolactone, dosing in dermatology, precautions to consider, and adverse effects. We also review new evidence that stresses the safety of long-term therapy and supports the use of this drug without the need for complementary testing in young women. We think that spironolactone merits a place among the medications commonly used in routine clinical practice.


Audiologic and vestibular assessment in patients with β-thalassemia major receiving long-term transfusion therapy.
Life-long transfusion therapy with chelators is a treatment choice for patients with β-thalassemia major. Some investigators have proposed auditory impairment related to the use of deferoxamine, but the mechanisms remain unclear and whether or not deferiprone has similar side effects needs to be evaluated. Thirty-seven patients with β-thalassemia major who received regular transfusion in our hospital were enrolled. Chelation agents, including deferoxamine and deferiprone, were used. To assess audiologic function, otoscopy, pure tone audiometry (PTA), tympanometry, transient evoked oto-acoustic emission (TEOAE), and auditory brainstem response (ABR) were conducted. Bithermal caloric test was performed to evaluate vestibular function. All of the 37 patients had normal findings on otoscopic evaluation and their tympanograms were type A. Thirteen patients (35.1%) had hearing impairment at one or more frequencies as detected by PTA. Compared to those without hearing impairment, patients with hearing impairment had lower serum ferritin levels (P = 0.01). Seven of 21 patients (33.3%) failed to pass the TEOAE, while 13 (61.9%) had abnormal ABR findings. Sixteen patients (80%) had canal paresis in the caloric test. The incidence of auditory impairment and vestibular dysfunction was high in patients with β-thalassemia major receiving long-term transfusion therapy. Potential lesions of auditory impairment may exist anywhere along the auditory pathway, from the inner ear to the brainstem. Lower serum ferritin levels may be associated with hearing impairment. Therefore, regular check-ups of serum ferritin levels and periodic audiologic assessment are mandatory.


Immunohistopathological characterizatin of spontaneous metastases in a human lung mucoepidermoid adenocarcinoma (HLMC) xenograft.
The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.


Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles.
Liver fibrosis results from the hepatic accumulation of the extracellular matrix accompanied by a failure of the mechanisms responsible for matrix dissolution. Pathogenesis of liver fibrosis is associated with many proteins from different cell types. In the present study, in silico molecular docking analysis revealed that curcumin may inhibit the fibrosis-mediating proteins PDGF, PDGFRB, TIMP-1, and TLR-9 by direct binding. Nano-formulation can overcome curcumin problems, increasing the efficacy of curcumin as a drug by maximizing its solubility and bioavailability, enhancing its membrane permeability, and improving its pharmacokinetics, pharmacodynamics and biodistribution. Therefore, green silver nanoparticles (AgNPs) were synthesized in the presence of sunlight by means of the metabolite of Streptomyces malachiticus, and coated with curcumin-chitosan mixture to serve as a drug delivery tool for curcumin to target CCl4-induced liver fibrosis mouse model. Fibrosis induction significantly increased hepatic gene expression of COL1A1, α-SMA, PDGFRB, and TIMP1, elevated hepatic enzymes, increased histopathological findings, and increased collagen deposition as determined by Mason's trichrome staining. Treatment with naked AgNPs tended to increase these inflammatory effects, while their coating with chitosan, similar to treatment with curcumin only, did not prevent the fibrogenic effect of CCl4. The induction of liver fibrosis was reversed by concurrent treatment with curcumin/chitosan-coated AgNPs. In this nano form, curcumin was found to be efficient as anti-liver fibrosis drug, maintaining the hepatic architecture and function during fibrosis development. This efficacy can be attributed to its inhibitory role through a direct binding to fibrosis-mediating proteins such as PDGFRB, TIMP-1, TLR-9 and TGF-β.


Pneumatic separation for crushed spent lithium-ion batteries.
Pneumatic separation was used to separate the valuable current collectors and harmful separators in spent lithium-ion batteries (LIBs) to avoid the plastic pollution caused by the separators in this study. Theoretical calculations for suspension velocities of the current collectors and separators indicate that they could be separated under special conditions. Furthermore, a special Z-shaped pneumatic separator was used to separate the current collectors and separators for the first time. Experiments for manually cut samples indicate that the efficiency of pneumatic separation is approximately 100% with the sizes and airflow velocities in the range of 3-4 cm and 6.96-7.8 m/s, respectively. Furthermore, industrial experiments of pneumatic separation indicate that the recoveries of the current collectors and separators are approximately 99.23% and 98.64%, respectively. Computer simulations of the separation process indicate that the turbulence and the changes in high-speed zones in the pneumatic separator benefit the separation of current collectors and separators. In conclusion, pneumatic separation is a promising technology to separate crushed current collectors and separators.


The role of geography and distance on physician follow-up after a first hospitalization with a diagnosis of a schizophrenia spectrum disorder: A retrospective population-based cohort study in Ontario, Canada.
Timely follow-up after hospitalization for a schizophrenia spectrum disorder (SSD) is an important quality indicator. We examined the proportion of individuals who received physician follow-up within 7 and 30 days post-discharge by health region and estimated the effect of distance between a person's residence and discharging hospital on follow-up. We created a retrospective population-based cohort of incident hospitalizations with a discharge diagnosis of a SSD between 01/01/2012 and 30/03/2019. The proportion of follow-up with a psychiatrist and family physician within 7 and 30 days were calculated for each region. The effect of distance between a person's residence and discharging hospital on follow-up was estimated using adjusted multilevel logistic regression models. We identified 6,382 incident hospitalizations for a SSD. Only 14.2% and 49.2% of people received follow-up care with a psychiatrist within 7 and 30 days of discharge, respectively, and these proportions varied between regions. Although distance from hospital was not associated with follow-up within 7 days of discharge, increasing distance was associated with lower odds of follow-up with a psychiatrist within 30 days. Post-discharge follow-up is poor across the province. Geospatial factors may impact post-discharge care and should be considered in further evaluation of quality of care.


Application of gap-constraints given sequential frequent pattern mining for protein function prediction.
Predicting protein function from the protein-protein interaction network is challenging due to its complexity and huge scale of protein interaction process along with inconsistent pattern. Previously proposed methods such as neighbor counting, network analysis, and graph pattern mining has predicted functions by calculating the rules and probability of patterns inside network. Although these methods have shown good prediction, difficulty still exists in searching several functions that are exceptional from simple rules and patterns as a result of not considering the inconsistent aspect of the interaction network. In this article, we propose a novel approach using the sequential pattern mining method with gap-constraints. To overcome the inconsistency problem, we suggest frequent functional patterns to include every possible functional sequence-including patterns for which search is limited by the structure of connection or level of neighborhood layer. We also constructed a tree-graph with the most crucial interaction information of the target protein, and generated candidate sets to assign by sequential pattern mining allowing gaps. The parameters of pattern length, maximum gaps, and minimum support were given to find the best setting for the most accurate prediction. The highest accuracy rate was 0.972, which showed better results than the simple neighbor counting approach and link-based approach. The results comparison with other approaches has confirmed that the proposed approach could reach more function candidates that previous methods could not obtain.


Prediction of cure and risk of hypothyroidism in patients receiving 131I for hyperthyroidism.
There is little consensus regarding the most appropriate dose of radioiodine ((131)I) to be administered to patients with hyperthyroidism. To compare the efficacy of fixed dose regimens of (131)I in curing hyperthyroidism and to define simple clinical and biochemical factors that predict outcome in individual patients. Consecutive series of hyperthyroid subjects treated with (131)I. Single Secondary/Tertiary Care Hospital Clinic. A total of 1278 patients (1013 females and 262 males, mean age 49.7 years) presenting with hyperthyroidism between 1984 and 2006. Treatment with (131)I using a fixed dose regimen. Probability of cure and risk of development of hypothyroidism following a single dose of (131)I. Patients given a single dose of (131)I of 600 MBq (n = 485) had a higher cure rate (84.1%) compared with those receiving either 370 MBq (74.9%, P < 0.001) or those given 185 Bq (63%, P < 0.001). An increased incidence of hypothyroidism by 1 year was evident with higher doses (600 MBq: 60.4%; 370 MBq: 49.2%, P = 0.001; 185 Bq: 38.1%, P < 0.001). Binary logistic regression analysis identified a 600 Bq dose of (131)I [adjusted odds ratio, AOR 3.33 (2.28-4.85), P < 0.001], female gender [AOR 1.75 (1.23-2.47), P = 0.002], lower presenting serum free T4 concentration [AOR 1.01 (1.01-1.02), P < 0.001] and absence of a palpable goitre [AOR 3.33 (2.00-5.56), P < 0.001] to be independent predictors of cure. Similarly, a 600 MBq dose [AOR 3.79 (2.66-5.38), P < 0.001], female gender [AOR 1.46 (1.05-2.02), P = 0.02], younger age [AOR 1.03 (1.02-1.04), P < 0.001], absence of a palpable goitre [AOR 3.85 (2.38-5.88), P < 0.001] and presence of ophthalmopathy [AOR 1.57 (1.06-2.31), P = 0.02] were identified as independent factors predicting the probability of development of hypothyroidism at one year. Based on these findings, formulae to indicate probability of cure and risk of hypothyroidism for application to individual patients were derived. Simple clinical/biochemical criteria can be used to predict outcome after (131)I treatment. These factors determine that males, those with severe biochemical hyperthyroidism, and those with a palpable goitre require larger doses (600 MBq) in order to achieve cure.


Post-exercise diastolic stunning detected by velocity vector imaging is a useful marker for induced ischemia in ischemic heart disease.
Recently, post-exercise diastolic stunning (PES) has been reported as a new clinical marker of induced ischemia. Velocity vector imaging (VVI) has been developed to visualize regional wall motion abnormalities based on vectors detected by the tissue tracking technique, which has the potential to visualize PES. Thus, the aim of this study was to evaluate the usefulness of PES detection by VVI as an objective marker of ischemia compared to stress thallium-201 (Tl-201) single photon emission computed tomography (SPECT). We studied consecutive patients who were scheduled to undergo exercise stress Tl-201 SPECT for the diagnosis of ischemic heart disease. Transthoracic echocardiography was recorded digitally before and 20 min after exercise for Tl-201 SPECT, and the data were used subsequently for VVI analysis. We defined PES regions as those with new abnormal vectors observed during isovolumic relaxation. After excluding 14 patients with old myocardial infarction and/or atrial fibrillation, echocardiograms suitable for VVI analysis were obtained from 62 of 65 patients (feasibility, 95 %; 44 men; mean age, 64 ± 11 years). SPECT revealed induced ischemia in 20 patients, whereas VVI identified PES in 18 patients. VVI detected inducible ischemia with 85 % sensitivity and 98 % specificity compared to SPECT. VVI detection of PES is a new clinical tool for induced ischemia. Regional diastolic wall motion abnormalities following induced ischemia can be noninvasively detected by VVI.


Plasmodium falciparum: red blood cell binding studies using peptides derived from rhoptry-associated protein 2 (RAP2).
Plasmodium falciparum rhoptry-associated proteins 1 (RAP1) and 2 (RAP2) are antigens presenting themselves as candidates for a subunit malaria vaccine. RAP2 protein, non-overlapping, consecutive peptides were synthesised and tested in red blood cell (RBC) binding assays to identify their receptor-ligand interaction in recognising RAP2 regions involved in the in vitro merozoite invasion process. Four high activity binding peptides (HABPs) were identified in the resulting 20 peptides. Peptides 26220 ((61)NHFSSADELIKYLEKTNINT(80)), 26225 ((161)IKKNPFLRVLNKASTTTHAT(180)) and 26229 ((241)RSVNNVISKNKTLGLRKRSS(260)) were located in the amino terminal and central part of the protein and HABP 26235 ((361)FLAEDFVELFDVTMDCYSRQ(380)) was located at the carboxy terminal. All these HABPs showed saturable binding and presented dissociation constants between 500 and 950 nM; the number of binding sites per RBC ranged from 48,000 to 160,000. High binding peptides' critical amino acids involved in RBC binding were determined by competition binding assays; their amino acids appear in bold in the sequences shown above. SDS-PAGE results showed that peptides 26220, 26225 and 26229 had at least two different sets of 62 and 42 kDa HABP receptors on RBCs and that peptide 26235 had at least two different sets of 77 and 62 kDa. HABPs inhibited in vitro merozoite invasion by between 54% and 94% at 200 microM, suggesting that these RAP2 peptides are involved in the in vitro P. falciparum invasion process.


Restraint, disinhibition and food-related processing bias.
This study examined associations between restraint, disinhibition and food-related processing bias (FPB, assessed by the emotional Stroop task) in males and females in the UK, Greece and Iran. Results showed high restraint was associated with higher FPB. However, high restrained current dieters showed lower FPB that high restrained non-dieters. There was no significant difference in FPB for those showing high versus low disinhibition. Results are discussed in relation to theories of incentive salience and current concerns.


Lewis Basicity of Nitrogen-Doped Graphite Observed by CO2 Chemisorption.
The characteristics of CO2 adsorption sites on a nitrogen-doped graphite model system (N-HOPG) were investigated by X-ray photoelectron and absorption spectroscopy and infrared reflection absorption spectroscopy. Adsorbed CO2 was observed lying flat on N-HOPG, stabilized by a charge transfer from the substrate. This demonstrated that Lewis base sites were formed by the incorporation of nitrogen via low-energy nitrogen-ion sputtering. The possible roles of twofold coordinated pyridinic N and threefold coordinated valley N (graphitic N) sites in Lewis base site formation on N-HOPG are discussed. The presence of these nitrogen species focused on the appropriate interaction strength of CO2 indicates the potential to fine-tune the Lewis basicity of carbon-based catalysts.


Excessive gestational weight gain over multiple pregnancies and the prevalence of obesity at age 40.
Although several studies have found an association between excessive gestational weight gain (GWG) and obesity later in life, to the best of our knowledge, no studies have explored the role of GWG events across the life course. We describe how the prevalence of midlife obesity (BMI⩾30 at age 40 or 41) among women varies by life course patterns of GWG (using 2009 IOM guidelines) in the USA's National Longitudinal Survey of Youth 1979 cohort. Among women who reported 1-3 births before age 40, the prevalence of midlife obesity increased with a rising number of excessive GWG events: from none (23.4%, n=875) to one (37.6%, n=707), from none (23.4%, n=875) to two (46.8%, n=427) and from none (23.4%, n=875) to three (54.6%, n=108), P<0.00005 for trend. Obesity prevalence was similar for the same number of excessive GWG events, regardless of parity. No clear pattern emerged for the sequencing of excessive GWG event(s) and later obesity. In our descriptive exploratory study, excessive GWG events appear to be associated with increased prevalence of obesity for parous women, suggesting the importance of preventive interventions regardless of timing of pregnancy-related weight changes over the life course.


Hemostatic response to acute physical exercise in healthy adolescents.
The chronic and immediate post-exercise responses in the hemostatic and fibrinolytic systems have been shown to be variable and reflect differing adaptations with ageing and responses to exercise protocols. This study investigated the effects of acute and exhaustive exercise on the amplitude and duration of hemostatic and fibrinolytic responses in young adolescent males. The sample comprised 10 sedentary boys (13.2+/-0.5 years, 55.8+/-11.3kg, 165.7+/-7.4cm), who had not exercised or received any medication for at least 2 weeks before the experiments. The subjects performed exhaustive stepping exercise, consisting of 1s up and down cycles to fatigue. When the subjects were unable to maintain the required stepping rhythm, they were given a 30s recovery period. Following each 30s recovery participants recommenced the stepping cadence until fatigue prevented them continuing. Venous blood samples were drawn before and immediately, 1 and 24h after exercise to assess the following coagulation and fibrinolytic parameters: Platelet counts, activated partial thromboplastin time (aPTT), prothrombin time (PT), coagulation factor VIII (FVIII:C), von Willebrand factor (vWF), fibrinogen concentration, thrombin-antithrombin complex (TAT), D-dimer, plasminogen activator inhibitor (PAI-1), and tissue-type plasminogen activator (t-PA). Immediately following exercise, platelet counts, aPTT, FVIII, vWF and t-PA were significantly elevated in contrast to PAI-1, which decreased significantly until 1h after exercise. FVIII and platelet counts were elevated at 1 and 24h after exercise, respectively. Only the parameters FVIII and PAI-1 did not return to baseline values during the first hour after physical exercise. When compared to adults the results revealed different rates and ranges of coagulation and fibrinolysis parameters being activated by exhaustive exercise in this group of adolescents.


Nonoperative Management of Traumatic Aortic Pseudoaneurysms.
Current blunt thoracic aortic injury (BTAI) guidelines recommend early repair of traumatic pseudoaneurysms (PSAs) due to risk for subsequent aortic rupture. Recent analyses indicate that early repair is required only in the setting of high-risk features, while delayed repair is safe and associated with lower morbidity and mortality in appropriately selected patients. To evaluate the appropriate indications for nonoperative management (NOM) of traumatic PSAs, we performed a systematic review of studies reporting outcomes for this management strategy. We hypothesized that NOM is safe in appropriately selected patients with traumatic aortic PSAs. English language single- and multi-institutional series reporting NOM of traumatic thoracic aortic PSAs were identified by systematic literature search and review. A descriptive analysis was performed of NOM, with stratification by lesion size and patient follow-up. The primary outcomes were late aortic intervention, aortic-related death, and all-cause mortality. Eighteen studies, which included 937 patients with traumatic PSAs, were analyzed. One hundred ninety-one patients were managed nonoperatively. The primary indication for NOM was prohibitive risk for aortic repair due to severe comorbidities or concurrent injuries. Where reported, PSAs with <50% circumferential involvement accounted for 88% of lesions selected for NOM. Late interventions were required in 4% of patients. Inpatient aortic-related mortality was 2%, and all-cause inpatient mortality was 32%. Although survival at up to 4-7 years was reported, postdischarge follow-up after PSA NOM was limited to <1 year in most studies. NOM of traumatic aortic PSAs is a common practice in BTAI series reporting lesion-specific management, and is associated with low rates of treatment failure. These findings suggest that routine early repair may not be required for traumatic PSAs, particularly for lesions limited to <50% of the aortic circumference. Definitive repair can be delayed until patient stability and repair timing can be guided by assessment of lesion stability on follow-up imaging.


Surgery for pulmonary metastases from colorectal cancer: the importance of prethoracotomy serum carcinoembryonic antigen as an indicator of prognosis.
Several investigators have analyzed prognostic factors of surgical treatment for pulmonary metastases from colorectal cancer, but the results remain inconclusive. This study was performed to determine the prognostic implications of the prethoracotomy serum level of carcinoembryonic antigen (CEA) in relation to the postthoracotomy recurrent pattern among patients with this disease. A retrospective analysis of prognostic factors was undertaken in 100 patients who had consecutively undergone initial surgical resection for pulmonary metastases of colorectal origin. The overall 3- and 5-year survival rates were 62.2% and 49.4%, respectively. Univariate analysis revealed that the prethoracotomy serum CEA level and operative curability were strongly associated with prognosis, while in multivariate analysis, only the prethoracotomy serum CEA level was a significant prognostic indicator. Patients with a high level of prethoracotomy serum CEA more frequently exhibited recurrence in extrathoracic sites, especially in the brain. Before thoracotomy for pulmonary metastases from colorectal cancer, the serum CEA level was the most useful prognostic factor. Patients with elevated serum CEA level should undergo a careful prethoracotomy systemic survey and postthoracotomy follow-up for extrathoracic metastases, in particular brain metastases, and an appropriate combined therapeutic modality should be considered.


Effects of adding methods and modification types of cellulose on the physicochemical properties of starch/PBAT blown films.
This study revealed the relationship between cellulose types/adding methods and film properties, in which sodium carboxymethyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC), and microcrystalline cellulose (MCC) were added into starch/PBAT blown films in powder, aqueous solution, and emulsion forms, respectively. Cellulose interacted with starch networks via hydrogen bonds, and those added in emulsion form made more homogeneous film morphologies. MCC emulsion enhanced the film strength (40%) and modulus (149%) to the greatest extent, while comprehensively, HPMC emulsion possessed better reinforcement effects on the films, which increased mechanical properties (31% ~ 100%), moisture barrier (20%), oxygen barrier (93%), surface hydrophobicity (20%), as well as water resistance (12% ~ 76%). Findings supported the application of cellulose in high-throughput biodegradable films, and the high-content starch/PBAT blown films reinforced by HPMC emulsion had great potential in commercial packaging fields.


An online escape room used to support the growth of teamwork in health professions students.
Effective teamwork in the online environment is essential to patient care and safety. The need for training health professionals to work together on a virtual interprofessional team has become even more important since the start of the COVID-19 pandemic as telehealth, or the provision of virtual healthcare to patients, has become more common. This resource describes the development of an online escape room activity using free online resources. The activity aimed to enhance health profession students' abilities to communicate effectively, work together to complete a task, and develop knowledge of the unique roles of healthcare team members in a course dedicated to interprofessional education. Teams of five to seven students met online and completed seven puzzles to escape a virtual room. Results obtained from the pre-post surveys of 176 students across six disciplines showed the activity aided in increasing participants perceptions of their ability to communicate respectfully and work together to complete a task, while developing knowledge of the unique roles of members of the healthcare team, all components of the Interprofessional Education Collaborative (IPEC) Core Competencies. This activity lays the groundwork for collaborative, interprofessional activities, such as telehealth, which students will be exposed to in their futures, and the results infer that the activity can help to build collaboration among team members, even team members that are not in the same physical space.


Matrix metalloproteinase release from placental explants of pregnancies complicated by intrauterine growth restriction.
There is evidence of impaired placental development in intrauterine growth restriction (IUGR). Matrix metalloproteinases (MMPs) are extracellular matrix-degrading enzymes that are released by placental cells during tissue remodeling processes. We hypothesized 1) that release of MMP-2 and -9 is decreased and/or release of tissue inhibitors of metalloproteinases (TIMPs) is increased from placental explants in pregnancies complicated by IUGR and 2) that oxygen levels affect such release. Placental villous explants from normal (n = 7) and IUGR (n = 7) pregnancies were cultured at high (20%) and low (3%) oxygen levels for 24 hours. Supernatants were analyzed for MMP-2 and MMP-9 by zymography and for TIMP-1 and -2 by western blot analysis. : At 20% oxygen there was significantly reduced MMP-2 (P < .05) and TIMP-1 (P < .01) release and a trend for decreased MMP-9 release (P = .07) in explants from IUGR pregnancies compared with normal pregnancies; however, there were no differences at 3% oxygen. TIMP-2 was below detectable levels in all samples. Although MMP-2 and TIMP-1 release was significantly reduced at 3% compared with 20% oxygen in explants from both normal (P < .001; P < .05) and IUGR (P < .05) pregnancies, MMP-2 release changed less in IUGR compared with normal explant cultures. There were no significant effects of oxygen on MMP-9 release. Placental explants from IUGR pregnancies demonstrated reduced MMP-2, MMP-9, and TIMP-1 release compared with explants from normal pregnancies at high (20%) but not low (3%) oxygen.


Parents voice their experiences of caring for children with special healthcare needs amid the COVID-19 pandemic.
The purpose of this study was to understand the experiences of parents and caregivers of children with special healthcare needs during the COVID-19 pandemic. In this descriptive phenomenological study, the researchers used purposive and snowball sampling to recruit nineteen participants, ranging in age from 21 to 55 years of age until saturation was established. Colaizzi's method guided data analysis. Iterative examination of the interview transcripts, an audit trail, bracketing, and validation of findings with a subset of participants established trustworthiness. Navigating the COVID-19 Pandemic was the overarching theme. Four major themes emerged under Navigating the COVID-19 Pandemic as follows: Disruptions in Daily Life, Shifts in Daily Life, Innovations in Daily Life, and Surprising Silver Linings. This study elucidated an in-depth understanding of the positive and negative impacts of the pandemic on the lives of families living with a child with special needs. The COVID-19 pandemic profoundly affected families and parenting approaches. Parents of children with special healthcare needs in this study found day-to-day living especially difficult in similar and unique ways. For virtually all parents the pandemic added new challenges in meeting their child's physical, mental, social, and educational needs. Parents and caregivers revealed innovative ways of maintaining a sense of normalcy during the height of the pandemic. These findings demonstrate the importance of developing interventions and creating public health policies as we move beyond the current pandemic and plan for potential outbreaks in the future.


Reconstruction of the heart and the aorta for radical resection of lung cancer.
We report a single-center experience of resection and reconstruction of the heart and aorta infiltrated by lung cancer in order to prove that involvement of these structures is no longer a condition precluding surgery. Twenty-seven patients underwent surgery for lung cancer presenting full-thickness infiltration of the heart (n = 6) or the aorta (n = 18) and/or the supra-aortic branches (subclavian n = 3). Cardiac reconstruction was performed in 6 patients (5 atrium, 1 ventricle), with (n = 4) or without (n = 2) cardiopulmonary bypass, using a patch prosthesis (n = 4) or with deep clamping and direct suture (n = 2). Aortic or supra-aortic trunk reconstruction (n = 21) was performed using a heart-beating crossclamping technique in 14 cases (8 patch, 4 conduit, 2 direct suture), or without crossclamping by placing an endovascular prosthesis before resection in 7 (4 patch, 3 omental flap reconstruction). Neoadjuvant chemotherapy was administered in 13 patients, adjuvant therapy in 24. All resections were complete (R0). Nodal staging of lung cancer was N0 in 14 cases, N1 in 10, N2 in 3. No intraoperative mortality occurred. Major complication rate was 14.8%. Thirty-day and 90-day mortality rate was 3.7%. Median follow-up duration was 22 months. Recurrence rate is 35.4% (9/26: 3 loco-regional, 6 distant). Overall 3- and 5-year survival is 60.9% and 40.6%, respectively. Cardiac and aortic resection and reconstruction for full-thickness infiltration by lung cancer can be performed safely with or without cardiopulmonary bypass and may allow long-term survival of adequately selected patients.


Comparison of clinical and paraclinical characteristics of patients with urge, mixed, and passive fecal incontinence: a systematic literature review.
Two subgroups of fecal incontinence (FI) are described in literature and used in clinical practice. However, the pertinence of this classification of FI is still unknown as there are no clear established guidelines. To a better understanding, we performed a systematic review to characterize the different types of FI (active, passive, or mixed) on the basis of clinical presentation and complementary explorations. This systematic literature review was performed in reference to recommendations for systematic review using PRISMA guidelines without date restriction, until May 2020. This systematic review was performed without temporal limitation using MEDLINE-PubMed, Cochrane Library, and Google Scholar databases. Six hundred nine unique citations were identified from all the databases combined. Of those, 21 studies met the inclusion criteria, with 8 retrospective observational studies and 13 prospective observational studies. There was a lack of homogeneity in definitions of passive and urge (active) FI among studies. Prevalence of passive and urge FI was respectively of 4.0-5.0 and 15.0-35.0%. Clinical characteristics, physical examination, and endoanal imaging were not evaluated in most studies. In anorectal manometry, maximal squeeze pressure was higher in passive FI subgroup in most studies and results regarding maximal resting pressure remain discordant. There seemed to be no difference regarding first sensation volume and maximal tolerable volume among subgroups. A few studies evaluated pudendal terminal nerve motor latency with no difference among subgroups. There is a lack of well-conducted prospective studies comparing the different subtypes of FI with validated definitions in both clinical and paraclinical examinations.


Spatial proteomic characterization of HER2-positive breast tumors through neoadjuvant therapy predicts response.
The addition of HER2-targeted agents to neoadjuvant chemotherapy has dramatically improved pathological complete response (pCR) rates in early-stage, HER2-positive breast cancer. Nonetheless, up to 50% of patients have residual disease after treatment, while others are likely overtreated. Here, we performed multiplex spatial proteomic characterization of 122 samples from 57 HER2-positive breast tumors from the neoadjuvant TRIO-US B07 clinical trial sampled pre-treatment, after 14-21 d of HER2-targeted therapy and at surgery. We demonstrated that proteomic changes after a single cycle of HER2-targeted therapy aids the identification of tumors that ultimately undergo pCR, outperforming pre-treatment measures or transcriptomic changes. We further developed and validated a classifier that robustly predicted pCR using a single marker, CD45, measured on treatment, and showed that CD45-positive cell counts measured via conventional immunohistochemistry perform comparably. These results demonstrate robust biomarkers that can be used to enable the stratification of sensitive tumors early during neoadjuvant HER2-targeted therapy, with implications for tailoring subsequent therapy.