A man aged 60’s suffered nephrotic syndrome with IgM nephropathy seven years earlier. Four years later, immune-checkpoint inhibitors (ICPIs) were administered against metastasizing pulmonary adenocarcinoma. Sixty-two weeks after 21 ICPIs injections, the cancer vanished but nephrotic syndrome relapsed. Acute pancreatitis followed and usual interstitial pneumonia exacerbated, as late-onset immune-related adverse-events.

We present a case of Systemic capillary leak syndrome in a patient who underwent surgery for colon cancer perforating peritonitis. We treated the patient with plasma filtration with dialysis.

1.Ectomycorrhizal (ECM) roots are evolutionary strategies of plants for effective nutrient uptake under varying abiotic conditions. Formation and morphological differentiations of ECM roots are important strategies in foraging environments. However, little is known on how such strategies mediate the nutrients of the below- and aboveground tissues and the balances among nutrient elements across environmental gradients. 2.We studied the function of ECM symbiosis in Abies faxoniana across its distributional range in Southwest China. The effects of differential ECM strategies, i.e. the contact exploration type, the short-distance exploration type, and the medium-distance exploration type, and root tips functional traits, etc., on root and foliar N and P and N:P ratio were examined across natural environmental gradients. 3.The ECM symbionts preferentially facilitated P uptake in A. faxoniana under both N and P limitations. The uptakes of N and P were primarily promoted by the effectiveness of ECM roots, e.g. ECM root tips per unit biomass, superficial area of ECM root tips, the ratio of living and dead root tips, but negatively related to the ECM proliferations and morphological differentiations. Generally, plant N and P nutrients were always promoted by the contact exploration type, while negatively affected by the short-distance exploration type in A. faxoniana. Root and foliar N and P nutrients were expected to be affected by the medium-distance exploration type in dynamics. Especially, root P limitation could be relieved when the frequency of medium-distance exploration type up to c.15%, whilst root N limitation was strengthen when the frequency of medium-distance exploration type over 20%. 4.We suggest that both below- and above-ground nutritional traits of host tree species could be strongly affected by ECM symbiosis in natural environments. The ECM strategies responding to environmental conditions significantly affect the plant nutrient uptakes and trade-offs. ECM soil exploration types are the great supplementary mechanisms for plant nutrient uptake.

Background: The aim of this study includes to discuss the clinical, laboratory, and chest computed tomography (CT) in pediatric patients with 2019 novel coronavirus (COVID‐19) infection. Material and Methods: The clinical, laboratory, and chest CT features of 17 pediatric inpatients with COVID‐19 infection confirmed by pharyngeal swab COVID‐19 polymerase chain reaction(PCR). All clinical and laboratory data have been recorded and analyzed during march-june 2020 . Chest CT have been performed to all Covid 19 PCR confirmed patients and radiologicall view have been noted. Results: Seventeen pediatric patients with a history of close contact with COVID‐19 diagnosed family members included to the study. Fever (10/17, 58%) and cough (13/17, 76%) were the most common symptoms. For laboratory findings, c reactive protein elevation (15/17, 88%) seem to be the most finding. A total of 4 patients presented with unilateral pulmonary lesions (4/17, 23%), 9 with bilateral pulmonary lesions (9/17, 52%) and 13 cases showed bilateral diffuse covid pattern on chest CT (13/17, 76%). Non-spesific consolidation with was observed in 8 patients (8/17, 47%), ground‐glass opacities were observed in 11 patients (11/17, 64%), nodules were observed in 7 patients (7/17, 41%), and tiny nodules were observed in 2 patients (2/17, 11%). Conclusion: In pediatric patients with positive COVID‐19 nucleic acid test from pharyngeal swab samples; the early detection of lesions by CT can be efficient; in management and early treatment for pediatric patients. However; early chest CT screening and COVİD-19 PCR testing together can be more efficent in diagnose. Keywords: Covid-19, viral pneumenia, chest computed tomography (CT), childeren.

The novel coronavirus named SARS-CoV-2 caused human epidemic all over the world at breathtaking speed. It is of great concern for the research community to understand the evolutionary origin and molecular characteristics of this virus. With more and more isolates are sequenced, it is possible to estimate the genomic variation and evolution of SARS-CoV-2. In this study, 17,229 complete genomes of SARS-CoV-2 were analyzed to characterize the genomic diversity. Using Doc2vec algorithm, we got the the genome embeddings of SARS-CoV-2 isolates as well as its related virus species. The results showed that the distance estimated from genome embedding is different from sequence alignment. Additionally, a frequently happened mutations (C to T/U) in -25 upstream of the ORF1ab start codon were identified. On protein level, it seemed that the mutations appeared with unequal distribution among the proteins. ORF1ab, S, ORF3a, ORF8 and N proteins were easier to tolerate mutations while the other proteins showed high conservation among the isolates.

The sinoatrial node in medication-resistant inappropriate sinus tachycardia: to modify or to ablate?Khalil El Gharib1*1Hôtel-Dieu de France, Beirut, Lebanon*Author for correspondence: khalil.gharib@outlook.comKEYWORDS: IST, sinus node modification, sinus node ablation, radiofrequency ablation, surgical ablationNo conflict of interest to discloseFunding: noneInappropriate sinus tachycardia (IST) is defined as a resting heart rate >100 beats per minute (with a mean heart rate >90 beats per minute over 24 hours) associated with highly symptomatic palpitations(1). The syndrome is associated neither with structural heart disease nor with any secondary cause of sinus tachycardia(2) and evidence suggests that enhanced intrinsic automaticity of the sinoatrial node, which can be due to anti-β-adrenergic antibodies, is behind its genesis(3). However, it is benign in terms of clinical outcomes and echocardiographic evidence of ventricular dysfunction(4), being rarely associated with tachycardia-induced cardiomyopathy(3).Patients with IST are essentially treated with ß-blockers to alleviate their symptoms(5). Ivabradine, a drug that inhibits funny calcium channels, particularly abundant in the SA node, showed modest benefit, receiving class IIa recommen­dation in the treatment of IST(4). But, the duration of medical therapy might be indefinite, and, a considerable number of patients would respond inadequately, or have no response, even after prolonged therapy(5). Historically, such patients would have subtotal right atrial excision, atrioventricular junctional ablation with permanent pacemaker implantation, or chemical occlusion of the sinus node artery(6). These options are considered today unacceptable in this setting, and other therapeutic approaches should be unveiled when resistance to medical treatment appears.Electrophysiological study was initially purely diagnostic, but recent advances in technology have allowed us to intervene(7); patients with ventricular and supraventricular tachyarrhythmias are successfully treated with percutaneous catheter procedures. Of these, SA node ablation/ modification has been proposed as alternative approaches in IST that is not responding to medical treatment; trials reported auspicious results, highlighted here.Electrophysiologic mapping to the site of the earliest endocardial activation during either spontaneous sinus tachycardia or isoproterenol-induced sinus tachycardia has rendered these procedures feasible(8). Additionally, combination with intracardiac echocardiography permitted a more accurate electrophysiologic and anatomic localization of the sinoatrial node(9).Sinus node modification is not a focal ablation, but requires complete abolition of the cranial portion of the SA node complex, the one that exhibits the most of the autonomic activity(9). It is defined as successful when the heart rate decreases by 30 beats per minute (bpm) during isoproterenol infusion(8). Short-term success was also defined by other investigators when there was a reduction of the baseline sinus rate to less than 90 bpm and the sinus rate during isoproterenol infusion by more than 20% or by 25%(8). The acute success rate for modification has been varying between 76 and 100 % across trials, while long-term clinical outcomes are modest at best, with reported freedom from IST ranging from 23 to 85%(10).Complications specific to SA node modification include superior vena cava (SVC) syndrome, diaphragmatic paralysis, and sinus node dysfunction(10). And while modification with conventional methods has its setbacks, modification using laser energy can be considered in the setting of IST. This modality creates clear-cut homogenous transmural lesions of the myocardium that comprises the scattered “functional” SA node(11). The burnt myocardium will then heal into a dense fibrous scar, decreasing potential amplitudes. And when adapting laser energy settings to the thickness of the myocardial wall, collateral dam­ages such as esophageal fistulae, lung burns, and phrenic nerve palsy will be avoided(11); thus, this technique may prove itself as a new intriguing alternative for the safe and effective treatment of IST.SA node modification is apt in achieving acute reductions in postprocedural heart rate. However, and as aforementioned, success rates are suboptimal in terms of symptomatic control with a significant recurrence rate(12). Catheter ablation aiming at either total exclusion and obliteration of the SA node has been described and performed, success being defined as a slowing of >50% from the baseline rate of tachycardia along with a junctional escape rhythm(12). With radiofrequency (RF) applications, the earliest local atrial activation time would shift from a cranial location to a more caudal one, usually at the mid-lateral right atrium(5). Reviews have reported that acute success rates were consistently to be as high as 88.9%, with an overall frequency of recurrence of 19.6%, the latter occurring within a wide range of post-ablation intervals, anywhere from a few weeks to several months after the procedure(12). Additionally, Takemoto and colleagues documented a significant drop in B-type natriuretic peptide levels, 6 to 12 months after ablation, suggesting fewer stretching shears on cardiac muscle.Two types of response of the sinus tachycardia to RFA were observed across studies, whether a step-wise reduction in sinus rate accompanying migration of the site of earliest atrial activation in a cranial-caudal direction along the lateral right atrial wall, or an abrupt drop in heart rate in response to RFA at a focal site of earliest atrial activation(13).However, RFA of inappropriate sinus tachycardia requires a large number of applications of radiofrequency energy and is, as in SA node modification, associated with a high recurrence rate(13). Complete remission is achieved only in approximately 50% of patients in some studies(14); longer history of IST and those reporting near syncope/syncope having a higher probability of recurrence(15).While other studies have shown that RF ablation of the SA node can achieve even longer-term reductions in the sinus rate and relief of symptoms in two-thirds of patients with drug-refractory, inappropriate sinus tachycardia(13), aiming specific sites related to the SA node should be elaborated, for better and optimal outcomes Killu and colleagues created a lesion in the arcuate ridge resulting in complete abolition of the tachycardia, since arrhythmias arising in this region may exhibit both electrocardiographic and clinical similarities to IST(16). This has led to consider ablation of the arcuate ridge as a treatment of refractory IST, necessitating larger trials to confirm its potential role.Phrenic nerve injury is a severe and dreaded complication of SN ablation(12). Pericarditis, right diaphragmatic paralysis, and SVC syndrome are other undesirable side effects of the procedures, variously reported in studies. but a common complication was observed in them all, atrial tachyarrhythmias(12). It has been hypothesized that myocardial pathology, such as inflammation and fibrosis, considered iatrogenic due to the ablation procedures, may be promoting arrhythmias both in the region of the SA node, as well as in remote locations(12). Through multivariable analysis, higher resting heart rates post-ablation and smaller cranial-to-caudal shifts have been defined as predictors of atrial arrhythmias(15). In conclusion, catheter ablation could be considered an effective treatment for highly symptomatic, drug-refractory patients, even for those who did not respond to SA node modification(5).The sinus node is located close to the epicardial surface and catheter-based ablations do not always make full-thickness lesions across the atrial muscle, leading to failure of the ablation(17), besides the numerous trabeculae and the widely variable anatomy.Surgical ablation is not a first-line or routine management strategy for IST, but it has been proposed when IST resists or recurs after SN modification/ endocardial ablation(17). Effectively, in several studies, epicardial lesions, through a single small incision in one of the intercostal spaces, successfully slowed heart rate and shifted activation to a more caudal location, and surprisingly, subsequent endocardial lesions led to an even greater drop in heart rate and more caudal site of earliest activation(18). These outcomes were again replicated when using minimally invasive thoracoscopic ablation of the epicardial site of the SA node, concluding of the promising efficacy and the safety of this approach, since it preserves the phrenic nerve(17), although continued follow-up after surgery is required.Medication-resistant IST remains a medical challenge for physicians and cardiologists; and in the era of great advances in interventional cardiology, its treatment remains debatable. Sinus node modification/ ablation is not recommended as first-line therapy in IST, this procedure should be considered only in drug-refractory patients who have severe symptoms(13). Although the number of patients in the available studies is generally small, both procedures have documented an encouraging success rate in the short-term, while being less impressive in the long-term. It has been hypothesized that this discrepancy is due to the relatively large potential area of atrial pacemaker cells(18); modification or ablation may fail to ablate or isolate all the pathways that comprise the functional SA node because they often target the anatomic part and the area of earliest atrial activation(19). Others have explained that the long-term slowing in rhythm fails because these procedures inconsistently produce transmural lesions in the right atrium. Surgical treatment of IST has proposed a solution to the latter conflict when isolating the SA node with a wide cuff of surrounding atrial muscle(19). And with the advent of bipolar RF clamps and minimally invasive cardiac surgical techniques with thoracoscopic guidance, this approach appears more appealing than before, especially when combined with endocardial ablation(19). But again, current data specifies employing these techniques in highly selected cases.

[] Source: Unsplash CC0 Artikel pendek ini berawal dari mini seri The Wonderful World of Chocolate yang tayang di Natgeo. Walaupun saya adalah penggemar kopi, tapi saya adalah juga pengamat coklat. Dalam episode-episode tersebut dikisahkan perkembangan inovasi coklat sejak tahun 1920an. Berawal dari buah terlarang yang hanya boleh dikonsumsi oleh para raja, mesin pengolah coklat yang ditemukan secara tidak sengaja, perpecahan keluarga yang berujung kepada coklat batangan yang terkenal di dunia, hingga dongeng tentang Willy Wonka, seorang pemilik pabrik coklat yang nyentrik. [] Source: Unsplash CC0 Kalau Anda melihat coklat sekarang sebagai sebuah sumber kebahagiaan, dulu coklat dari pohon kakao ditemukan oleh peradaban Maya dan Aztec di tahun 1800an SM. Kakao kemudian berkembang sebagai sumber perpecahan, selayaknya rembah-rempah di Kepuluan Banda yang menjadi komoditas rebutan antar bangsa penjelajah. Tercatat Columbuslah yang membawa kakao dari benua baru Amerika ke daratan Eropa dalam perjalanannya yang ke-4. Singkat cerita bergeser ke tahun 1920, kakao ternyata bisa diolah jadi makanan dan minuman setelah alat penggilingnya ditemukan pada tahun 1729. Pada tahun 1930an industri coklat makin berkembang dengan variasi produk dan kemampuan produksi yang makin banyak. Ini didukung dengan beragamnya invensi dalam pengolahan coklat. Merek—merek seperti Cadbury, Lindt, Hershey’s muncul di periode ini. [] Source: Unsplash CC0 Geser ke dunia masa kini. Industri coklat tidak banyak berubah dibanding saat era awal fabrikasi coklat di tahun 1920an. Hanya lebih besar skalanya, lebih cepat prosesnya, dan lebih luas jangkauan produksinya. APA BENANG MERAHNYA? Yang pertama adalah uang privat Perkembangan industri dan inovasi coklat dibiayai dengan dana privat para pemiliknya. Contoh saja, Frank Mars, warga Amerika Serikat yang hijrah ke Inggris untuk mendefinisikan ulang coklat dengan membuat coklat batang Mars, bermodalkan 50 ribu dolar dari orang tuanya. Walaupun Frank Mars pergi karena marah kepada ortunya, sepertinya doa ortu tetap menyertainya. Perusahaan coklatnya saat ini bernilai tidak kurang dari 90 milyar dolar. Yang kedua adalah paten Di dalam sekotak Hershey’s atau Cadbury yang menyenangkan terdapat dunia persaingan yang penuh dengan paten. Paten berkaitan dengan proses, resep, mesin pengolah, mesin pengepakan, hingga bentuk kemasan. Persaingan bisnis juga melatarbelakangi rasa coklat yang menggugah rasa. Cerita yang mirip juga terjadi di dunia usaha minuman. Konon desain botol Coca Cola tidak dibuat oleh perusahaan itu, tetapi oleh perusahaan pengemasannya. Dulu di awal usahanya, pemilik Coca Cola merasa kerepotan menangani proses pengemasannya. Jadi proses itu diserahkan ke pihak lain. Ketika perusahaan pengepakan itu menemukan desain botol yang cantik sekaligus fungsional, maka Coca Cola pun membeli patennya, seharga 1 dolar. Ini karena pihak pengepakan tidak pernah mengira desainnya yang sederhana itu akan menjadi legenda. 🙂 ya begitulah. [] Source: Unsplash CC0 Intinya dunia coklat seperti halnya dunia usaha yang padat modal privat lainnya, penuh dengan persaingan yang salah satunya berwujud paten. Siapa yang menemukan sesuatu lebih dulu, akan menyimpannya rapat-rapat sebelum patennya disetujui. APA HUBUNGANNYA DENGAN SAINS TERBUKA? Ada hubungannya, yakni fakta bahwa mayoritas dana riset Indonesia didanai oleh negara, serta permintaan negara sendiri untuk menghasilkan banyak paten dari dana riset itu, melalui berbagai regulasinya. Bahkan berbagai riset yang terkait dengan Covid termasuk yang ingin dipatenkan. Jumlah paten memang telah lama dipakai sebagai indikator kemajuan inovasi suatu perguruan tinggi, dan pada akhirnya secara akumulatif akan mencerminkan inovasi pada tingkat negara. Berbagai sosialisasi dan himbauan oleh pimpinan perguruan tinggi selalu memuat pentingnya paten. Kenapa paten tidak sesuai dengan semangat sains terbuka? Ya tidak sesuai, terutama bila suatu paten berawal dari riset yang didanai negara. Runutannya begini: - Setiap riset yang didanai pasti membutuhkan proposal. - Pada setiap proposal selalu ditonjolkan berbagai masalah yang terjadi di masyarakat, baik skala lokal, nasional, dan internasional, serta apa dampaknya bila riset tersebut tidak dilaksanakan (karena tidak lolos seleksi). - Kemudian ketika proposal lolos seleksi dan didanai, hasil akhirnya akan dipatenkan. - Kenapa harus dipatenkan? Menurut regulasi adalah untuk melindungi Hak Kekayaan Intelektual (HKI) penemunya (inventornya). Ini juga akan kami bahas di bawah. [] Agar dapat dipatenkan, maka hasil invensi itu tidak dapat dipublikasikan terlebih dahulu. Ini sudah sering disampaikan berbagai nara sumber. Salah satunya adalah berikut ini. “Juldin menjelaskan bahwa hasil penelitian yang berpotensi paten harus didaftarkan patennya terlebih dahulu dibandingkan dengan publikasi di jurnal untuk memastikan agar perlindungan patennya didapatkan. “Berdasarkan UU Paten, jika lebih dari enam bulan setelah publikasi di jurnal tidak didaftarkan patennya, maka invensi tersebut tidak dianggap baru dan tidak dapat diberikan paten.” Lanjutnya.” (https://risbang.ristekbrin.go.id/publikasi/berita-kegiatan/kemenristekdikti-informasi-hasil-penelitian-yang-berpotensi-paten-jangan-disebarkan-sebelum-dilindungi-kekayaan-intelektualnya/) Jadi artinya hasil riset yang awalnya bertujuan untuk memberikan solusi bagi masyarakat, harus ditunda publikasinya, dengan alasan agar dapat dipatenkan. Berapa lama proses paten, saya kurang tahu. Mohon pendapat dari pembaca yang memahaminya. Artinya masyarakat perlu menunggu, sehingga dampak buruk yang disampaikan dalam proposal bisa saja terlanjur terjadi. Padahal yang memberi dana riset adalah masyarakat melalui berbagai instrumen, salah satunya pajak. Ada temuan yang tidak dapat dipatenkan Lebih jauh lagi, ketika banyak narasumber menyampaikan pentingnya paten dan bahwa paten adalah salah satu luaran riset yang tercantum dalam regulasi, mereka lupa bahwa ada beberapa jenis invensi/temuan yang tidak dapat dipatenkan menurut UU 13/2016 tentang Paten, ada beberapa jenis invensi yang tidak dapat dipatenkan: A. proses atau produk yang pengumuman, penggunaan, atau pelaksanaannya bertentangan dengan peraturan perundang-undangan, agama, ketertiban umum, atau kesusilaan; B. metode pemeriksaan, perawatan, pengobatan dan/ atau pembedahan yang diterapkan terhadap manusia dan/atau hewan; C. teori dan metode di bidang ilmu pengetahuan dan matematika; D. makhluk hidup, kecuali jasad renik; atau E. proses biologis yang esensial untuk memproduksi tanaman atau hewan, kecuali proses nonbiologis atau proses mikrobiologis. Barang privat dan barang publik Sebelumnya saya sampaikan kembali bahwa artikel ini membahas paten yang risetnya didanai negara. Adapun kalau risetnya didanai oleh swasta, tidak perlu dibahas di sini, karena para prinsipnya idealnya barang privat (_private goods_) berasal dari barang privat dan barang publik (_public goods_) berasal dari barang publik juga. [] Source: Unsplash CC0 Kalau yang kita bicarakan adalah obat yang dibuat oleh pabrik obat dengan uangnya sendiri, maka hak mereka untuk mematenkan itu. Namun perlu juga diperhatikan uraian di atas, tentang beberapa jenis barang yang tidak dapat dipatenkan. Nah sekarang, dengan berbagai prasyarat yang sangat kaku saat mengajukan paten, apakah bisa ketika sudah disetujui, sebuah paten dapat diperlakukan sebagai barang publik? Saya sudah mencoba mencari informasi, apakah sebuah paten dapat terdaftar sebagai milik suatu negara, bukan pribadi atau lembaga. Tapi belum berhasil menemukannya. Mohon juga ada yang menyampaikan kalau memang ada. Lantas bagaimana cara melindungi HKI pencipta? Ada banyak cara untuk riset yang dibiayai negara, dengan asumsi bahwa barang publik akan menghasilkan barang publik. Jadi tidak perlu ditutup-tutupi atau ditahan publikasinya. Kalau bisa bahkan harus sebanyak mungkin orang dapat membuat ulang invensi yang dihasilkan oleh riset negara. [] Source: Unsplash CC0 Yang paling mudah untuk melindungi HKI adalah menggunakan lisensi, salah satu yang dapat dipakai adalah lisensi Creative Commons. Para pembaca dapat mempelajari berbagai rujukan tentang lisensi CC ini. Bila dirasa kurang kuat, dapat ditambah dengan pendaftarannya ke Kemenhukham untuk mendapatkan sertifikat HKI. Walaupun sebenarnya ini tidak dibutuhkan, tapi ada banyak kolega saya yang merasa lebih yakin terlindungi bila telah mendaftarkan ciptaannya dan telah mendapatkan sertifikat ini. Semudah itukah? Iya, dengan kondisi bahwa barang publik akan menghasilkan barang publik. Bila ada pembaca yang lebih memahami lisensi terbuka, mohon dapat memberikan komentar. JADI APA PESAN UTAMANYA? Pesan utamanya sederhana, barang publik harus menghasilkan barang publik. Jadi kalau ada riset dibiayai publik, maka hasilnya adalah untuk publik, terutama bila hasilnya berkaitan langsung dengan hajat hidup orang banyak. Yang berat menurut saya adalah karena negaralah yang minta peneliti menghasilkan paten. 🙂 Siklus yang mudah diputus bila pembuat kebijakan memahaminya. [] Source: Unsplash CCO

A document by Julia Pastol. Click on the document to view its contents.

In this study, we aim to find out maternal and fetal outcomes in women with PH resulting from different causes and try to determine the risk factors related to adverse maternal and fetal outcomes. We extracted the data from the records: the demographic information, onset, course, clinical and echocardiographic details, maternal and fetal complications, management as well as obstetric data, which included complications, infant of low-birth weight. We compared the outcome based on the cause of disease and pulmonary hypertension pressure levels. 603 women were included in the final analysis, who were mainly had pulmonary hypertension secondary to congenital heart disease (66.0%) and 46 of whom had Eisenmenger syndrome (7.6%). The mortality was 3.0%, 56% of which was caused by Eisenmenger syndrome. The abortion rate was 8.3% and 32% of live newborns were born before term. Heart failure complicated 17.1% and fetal growth restriction 3.5% of pregnancies. Advanced medication was administered in an increasing number of patients. Morbidity was significantly increased in women with pulmonary hypertension associated with a pulmonary hypertension pressure ≥80 mmHg. The mortality rate was lower than previously reported. Nevertheless, in Eisenmenger syndrome, PH secondary to connective tissue disease and idiopathic PH, the maternal mortality is still very high. In addition to the use of PAH-targeted drugs, we believe that standardized maternal management strategies can also help reduce mortality, including screening for heart disease and effective transport of critically ill patients. The maternal and infant outcome is related to etiology and the severity of PASP.

We report a case of a 77-year-old female who underwent a mitral valve replacement 20 years earlier and now presented with progressive dyspnoea and a degenerated Mosaic mitral valve bioprosthesis. We performed a transapical transcatheter mitral valve-in-valve implantation, which was complicated by a myocardial tear at the apex due to frail tissue and the procedure was aborted. After recovery of this event, we decided to perform a hybrid procedure, which was a direct transatrial transcatheter mitral valve-in-valve implantation through a right mini thoracotomy. This procedure went uncomplicated and further recovery went uncomplicated.

Objective: This study aimed to evaluate the long-term outcome of patients with PDA associated with UAPA. Methods: Patients diagnosed with PDA associated with UAPA were retrospectively enrolled from January 2005 to June 2019. Clinical data, treatment and follow-up information were evaluated. Results: 11 patients (5 males and 6 females) were diagnosed with PDA associated with UAPA. Percutaneous closure was conducted in 9 patients successfully. The median age was 37 months. The mean diameter of the PDA and occluders were 5.3±1.8mm (range 2-8.1 mm), 11.5±3.9 mm (4-16 mm) respectively. The median in 5 patients with the pulmonary: systemic flow ratio (Qp:Qs) was 1.41(1.28-8.7) and total lung resistance was 12 wood (1.8-13.6) . The mean systolic pulmonary artery pressure was 68.3±19.1mmHg（42-105mmHg). In 5 patients with pre- and post-procedure catheter data, the systolic pulmonary arterial pressure decreased significantly after closure 77.0±20.2 v 58.8±17.5 mmHg (p = 0.024), and so was the mean pulmonary arterial pressure 58.2±14.6 v 39.0±14.1 mmHg (p = 0.18). The pulmonary artery pressure and heart size gradually decreased to normal in 8 patients, and the quality of life was significantly improved. The ratio of lung to systemic circulation pressure in all these patients was less than 0.75. Conclusions: In appropriate patients with PDA associated with UAPA, transcatheter closure of PDA has the potential to improve the pulmonary artery hypertension. The ratio of lung to systemic circulation pressure less than 0.75 may be important reference index for predicting whether the pulmonary artery pressure could be reduced to normal after occlusion.

Background: Despite advances in endoscopic transnasal transsphenoidal surgery (E-TNS) for pituitary adenomas (PAs), cerebrospinal fluid (CSF) leakage remains a life-threatening complication as it predisposes to meningitis and tension pneumocephalus. The purpose of the current study is to develop an accurate supervised ML model able to predict the risk of intraoperative CSF leakage by comparing different machine learning (ML) methods. Methods: A cohort of patients consecutively treated via E-TNS for PAs was selected. Clinical, radiological and endocrinological preoperative data were reviewed and elaborated through a features selecting algorithm. A customized pipeline of several ML models was programmed and trained in parallel; the best five models were included for further analyses. Selected risk factors were then used for training and hyperparameters optimization. Results: Intraoperative CSF leak occurred in 54 (22,6%) of 238 patients. Best risk’s predictors were: non secreting status, older age, x-, y- and z-axes diameters, ICD and R ratio. The random forest (RF) classifier outperformed other models, with an AUC of 0,84, high sensitivity (87%) and specificity (82%). Positive predictive value and negative predictive value were 69% and 93% respectively. F1 score was 0,87. Conclusion: A supervised machine learning prediction model able to identify patients at higher risk of intraoperative CSF leakage was trained and internally validated. The random forest classifier showed the best performance across all models selected by the authors. RF models might predict surgical outcomes in heterogeneous multimorbid and fragile populations outperforming classical statistical analyses and other machine learning models.

Objectives. We aimed to validate a Spanish version of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (SRBD-PSQ) in children living in a high-altitude Colombian city. Methods. In a prospective cohort validation study, patients aged between 2 and 18 years who attended the Ear, Nose, and Throat pediatric department of our institution for symptoms related to sleep-related breathing disorders had a baseline visit at enrollment, a second visit the day scheduled for the surgical intervention, and a follow-up visit at least three months after the surgical intervention. In these three visits, we gathered the necessary data for assessing the criterion validity, construct validity, test–retest reliability, internal consistency, and sensitivity to change of the Spanish version of the SRBD-PSQ. Results. In total, 121 patients were included in the analyses. The exploratory factor analysis (generalized least squares method, varimax rotation) yielded a four-factor structure, explaining 65.93% of the cumulative variance. The intraclass correlation coefficient (ICC) of the measurements was 0.887 (95% CI: 0.809–0.934), and the Lin concordance correlation coefficient was 0.882 (95% CI, 0.821-0.943). SRBD-PSQ scores at baseline were significantly higher than those obtained after adeno-tonsillectomy surgery (median [IQR] 11.0 [9.0- 14.0] vs. 4.00 [1.50- 7.0]; p<0.0001). Cronbach’s α was 0.7055 for the questionnaire as a whole. Conclusions. The Spanish version of the SRBD-PSQ has acceptable construct validity, excellent test-retest reliability and sensitivity to change, and adequate internal consistency-reliability when used in pediatric patients living at high altitude with symptoms related to sleep-related breathing disorders.

Objectives: To describe clinico-virological profile, treatment details, intensive care needs, and outcome of infants with acute viral bronchiolitis (AVB). Methodology: In this prospective study, 173 infants with AVB admitted to Pediatric emergency and Pediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India during November 2019 to February 2020 were enrolled. The data collection included clinical features, viruses detected, complications, intensive care needs, treatment, and outcome. Multivariate analysis was performed to determine independent predictors for PICU admission. Results: Patients had rapid breathing (98.8%), cough (98.3%), and fever (74%). On examination, tachypnea (98.8%), chest retractions (93.6%), respiratory failure (84.4%), wheezing (49.7%), and crepitations (23.1%) were observed. RSV and rhinovirus were predominant isolates. Complications were noted in 25% cases as encephalopathy (17.3%), transaminitis (14.3%), shock (13.9%), AKI (7.5%), myocarditis (6.4%), MODS (5.8%), and ARDS (4.6%). More than one-third cases required PICU admission requiring nasal cannula oxygen (11%), continuous positive airway pressure (51.4%), high flow nasal canula (14.5%), and mechanical ventilation (23.1%); nebulization (74%); antibiotics (35.9%); and vasoactive drugs (13.9%). The mortality was 8.1%. Underlying comorbidity; chest retractions, respiratory failure, and low oxygen saturation at admission; presence of shock; and need of mechanical ventilation were independent predictors of PICU admission. Isolation of virus or co-infection were not associated with disease severity, intensive care needs, and outcome. Conclusion: Among infants with AVB, RSV and rhinovirus were predominant; >1/3rd required PICU admission; and comorbidity; chest retractions, respiratory failure, low oxygen saturation; shock; and need of mechanical ventilation independently predicted PICU admission.

Background: Chitotriosidase (ChT) is an enzyme secreted by activated macrophages and neutrophils, in response to proinflammatory signals. There is growing evidence indicating that ChT activity reflects systemic inflammatory status. In this study, we aimed to investigate whether serum ChT activity is increased in patients with psoriasis and related comorbidities. Materials and Methods: This study included patients with psoriasis and healthy volunteers. All subjects underwent a laboratory investigation including serum ChT levels, complete blood count, erythrocyte sedimentation rate, C-reactive protein, and serum lipid levels. Results: 25 patients without comorbidity, 28 patients with comorbidity, and 52 healthy subjects were enrolled. The patients group showed statistically significant higher levels of ChT activity (23.5 ± 11.4 μmol / ml / h) compared to the healthy controls (17.5 ± 10.4/ μmol / ml / h) (p=0.015). ChT activity was also statistically significant higher in patients with comorbidity compared to patients without comorbidity (p = 0.042). Conclusions: Our data support the pathogenetic role of inflammatory processes induced by macrophage activation in psoriasis and related comorbidities. We believe that high ChT activity in patients with psoriasis may serve as a clue for the early prediction of possible related comorbidities.

Aims: The symptoms of menopause in postmenopausal women adversely affect the quality of life. Menopausal symptoms are more severe with comorbid disorders such as depression; it may be lighter in physically active people. The present study aimed to evaluate the relationship between menopausal symptoms and physical activity and depressive mood. Material and Method: 190 women under 65 years of age who were at least one year passed since their last menstrual period participated in the study. Sociodemographic data form, Menopause Symptom Rating Scale, International Physical Activity Questionnaire - Short Form and Beck’s Depression Inventory were applied to the participants. Results: It was seen that 51.6% (98 subjects) of the women who participated in the study had severe menopausal symptoms. 52.6% (100 subjects) of the participants were physically inactive, and their menopausal symptoms increased as the physical activity scale score decreased (p=0.001). Menopausal symptoms increased as the Beck’s Depression Inventory score increased (p<0.001). It was observed that depression inventory scores decreased as the level of physical activity increased (p<0.001). Conclusion: Adoption of regular physical activity habits by postmenopausal women and providing treatment to those with depression will contribute to alleviating the severity of menopausal symptoms.

Background: Meningioma is one of the most common tumors of central nervous system. Although genetic alterations have been linked to elevated risk of malignancy for meningioma patients, the incongruence between clinical outcomes and WHO grade classification still exist. Therefore, large-scale genome-wide expression profiles identifying reliable biomarkers remains incompletely investigated. Methods: In order to identify genes related to invasion and metastasis process in meningiomas, genome-wide profiles in 145 meningioma patients were identified using microarray datasets GSE12530, GSE16581 and GSE43290 from the Gene Expression Synthesis (GEO) database based on differential tissues expression. Protein-protein interaction (PPI) network were constructed and functional annotations of DEGs were evaluated using R software. In addition, differential expression and prognostic value of CLU on meningioma was evaluated using immunohistochemistry in WHO grade II-III meningioma from AHYMUN, a real-world cohort. Results: A total of 58 DEGs were significantly associated with malignant behaviours of meningioma. Next, CLU were identified as hub gene in the PPI network, showing markedly prognostic implications in 67 meningioma patients. Expression level of CLU significantly climbed with elevated WHO risk classification. Interestingly, 40 genes were screened according to differential CLU expression. Additionally, significant high expression level of CLU were found in meningiomas tissue than normal tissues, predicting significant poor prognosis for 100 meningiomas patients from AHYMUN cohort. Conclusion: In conclusion, this study first reveals novel role of CLU using genome-wide expression profiles in high-risk WHO grade of meningioma and significant prognostic value based on large-scale cohorts. This work laid the foundation for the targeted molecular therapies and provided new insights into the treatment and prognostic srategies of meningiomas.

Letter to the Editor, BJOG in Exchange

A 64-year-old man with severe aortic stenosis and mitral regurgitation presented to our emergency. He had a New York Heart Association class IV symptoms with EuroSCORE II of 20%. Heart team decide to perform an urgent TAVR. The patient commenced cardiogenic shock in operation room. A Venus 22mm balloon and A 26mm Venus A-Valve were performed immediately. Aortography and TEE showed a deep implantation, moderate to severe “supra-skirt” paravalvular aortic regurgitation (PAR) and mild prosthetic aortic valve stenosis. After evaluating the hemodynamic tolerability of PAR and the initial mitral regurgitation, the heart team decided to proceed with aortic valve replacement and mitral valve replacement rather than valve-in-valve TAVR.

Aim: The appendix has a complicated immune function, and appendectomy may derange the immune system. Studies on the relationship between appendectomy and subsequent inflammatory bowel disease (IBD) have been inconsistent. We conducted a nationwide cohort study consisting of individuals who underwent appendectomy to evaluate the incidence and risk of ulcerative colitis (UC) and Crohn’s disease (CD). Methods: We identified patients aged >20 years who underwent appendectomy between 2000 and 2012 from inpatient claims of the National Health Insurance Research Database (NHIRD) and assigned them to the appendectomy cohort. Then, we randomly selected patients without appendectomy in the NHIRD and assigned them to the comparison cohort in a frequency-matched 1:1 ratio based on sex, age, and index year. We tracked down all participants until IBD diagnosis, death, or the end of 2013. Cox models were used to estimate the hazard ratio (HR), and 95% confidence intervals (CIs) were used to compare the IBD risk between the appendectomy and comparison cohorts. Results: The appendectomy and comparison cohorts in the study consisted of 246 562 patients each. The appendectomy cohort exhibited a 2.23- and 3.48-fold higher risk of UC (adjusted HR = 2.23, 95% CI = 1.59-3.12) and CD (adjusted HR = 3.48, 95% CI = 2.42-4.99), respectively, than did the comparison cohort. UC and CD risks significantly increased in the appendectomy cohort regardless of whether appendicitis was present. Conclusion: Our study suggests that appendectomy increases UC and CD risks irrespective of appendicitis.

Repl enish ment for Demand & Inv entory P lanning is a way to effici ent ly manage flo w of the goods as th ey mov e throughout the entire supply chain from the manu factu rer to the supplier to warehouse and sh ipment location. It const antly check sto ck vs. demand. A good replenishment system help to avoid hu man errors, for inst ance mis sing to place an order in the system, o r ent er wrong informati on. An in telligent replenish ment system can be con fig ured to auto mate trigg ers to order/re-ord ering the go ods , s ugg est alt ernativ e app roaches to get the goods (e.g. Transfer of go ods from Di st ribut ion center or location instead of pu rchasing from th e supplier), it also facto rs in forecast changes in demand and adjusts the replenish ment ord ers. The to ol can overall improve service levels, gain effici ency, leads to reduce cost and improves customer sat isfacti on.The perseverance of this study is to recogni ze the element s of Materi als Requi rement Planning (MRP) and impl ement to our selected probl em. Mai n obj ective of MRP is to manage dependent demand items, high inv entory turnov er and lo w payabl e cost. A common and effecti ve problem which rise in Manufactu ring and small , medi um-Sized Firms and industri es was taken for understand and all possible facto rs are taken and dis cussed after th at th e solution procedure is appli ed and result is presented. This paper des crib es the impo rtance and featu res of go ods repl enish ment tool for Demand & Invento ry P lanning categorized as Material requi rements planning MRP using Dat a and Analytic. We are going to introdu ce entire list of the key featu res that are designed sp ecific as per th e requi rement of the Supply chain in the Oil and gas industry. Copyright © 2020, Farhana Sethi. This is an open access article distributed under the Creative Commons Attribution Lice nse, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Approximately 80% of obsessive–compulsive disorder (OCD) cases begin in childhood. Various genetic, psychological, sociological factors and biological mechanisms are involved in the etiology of OCD. To the best of our knowledge the relationship between inflammation and OCD is unclear. Chronic inflammation was shown to increase neopterin and decrease tetrahydrobiopterin (BH4) levels by activating the neopterin–BH4 pathway. In addition, studies have shown that it can be an important biomarker in psychiatric disorders. Objective: This study compared serum TGF-1β, TNF-α, IL-1β, IL-2, IL-6, IL-10, IL-17, neopterin, BH4, and nitric oxide (NO) levels between child and adolescent patients diagnosed with OCD and a healthy control group. Methods: The study included 29 patients diagnosed with OCD (comorbidity free, drug free) and 28 healthy children as an aged and sex matched control group. For the measurement of neurobiological markers, venous blood samples were collected, and analyzed by using enzyme-linked immunosorbent assay (ELISA). Results: All cytokine levels were found to be low, but this decrease was statistically significant only for TGF-1β. The neopterin and NO levels were significantly higher and BH4 significantly lower in children with OCD compared to the healthy control group. Conclusion: The results of our study show that the levels of TGF-1β and NO and the activation of the neopterin–BH4 pathway may be implicated in the pathophysiology of OCD. Additionally, anti-oxidant and BH4 adjuvant therapies should be investigated as treatment options for OCD.

For women with congenital vaginal agenesis and sexual needs, creating a functioning neovagina is a practical therapeutic schedule. Colpopoiesis using the sigmoid intestine were more reported in the literatures. Though the incidence of neovaginal prolapse (NP) is relatively low (3-8%), it does bring great inconvenience to patients, and expose gynecologists to tough challenges. Hereon, we report a case of NP 10 years after sigmoid colon vaginoplasty that was successfully repaired by laparoscopic sacro-colpopexy with a mesh, hoping to provide meaningful evidence for this rare situation.

Carotenoids play vital roles in the colouration of plant tissues and organs, particularly fruits; however, the regulation of carotenoid metabolism in fruits during ripening is largely unknown. Here, we show that red light (RL) promotes fruit colouration by inducing accelerated degreening and carotenoid accumulation in kumquat fruits. Transcriptome profiling reveals that a NAC family transcription factor, FcrNAC22 is specifically induced in RL-irradiated fruits. FcrNAC22 localizes to the nucleus, and its gene expression is up-regulated as fruits change colour. Results from dual luciferase, yeast one-hybrid (Y1H) assays and electrophoretic mobility shift assays (EMSAs) indicate that FcrNAC22 directly binds to and activates the promoters of three genes (i.e. FcrLCYB1, FcrBCH2 and FcrNCED5) encoding key enzymes in carotenoid metabolic pathway. Moreover, FcrNAC22 overexpression in citrus and tomato fruits as well as in citrus callus enhances expression of a dozen of carotenoid biosynthetic genes including the aforementioned three, accelerates plastid conversion into chromoplasts, and promotes colour change. Knock down of FcrNAC22 expression in transient transformed citrus fruits attenuates fruit coloration induced by red light. Taken together, our results demonstrate that FcrNAC22 is an important transcription factor that mediates RL-induced fruit colouration via upregulation of carotenoid metabolism in citrus and perhaps in other plants.