1.Teleworking Survey in Saudi Arabia: Reliability and Validity of Arabic Version of the Questionnaire
Heba Yaagoub ALNUJAIDI ; Mehwish HUSSAIN ; Sama’a H. ALMUBARAK ; Asma Saud ALFAYEZ ; Demah Mansour ALSALMAN ; Atheer Khalid ALSAIF ; Mona M. AL-JUWAIR
Journal of Preventive Medicine and Public Health 2022;55(6):578-585
		                        		
		                        			 Objectives:
		                        			This study aimed to adapt the survey questionnaire designed by Moens et al. (2021) and determine the validity and reliability of the Arabic version of the survey in a sample of the Saudi population experiencing teleworking. 
		                        		
		                        			Methods:
		                        			The questionnaire includes 2 sections. The first consists of 13 items measuring the impact of extended telework during the coronavirus disease 2019 (COVID-19) crisis. The second section includes 6 items measuring the impact of the COVID-19 crisis on self-view of telework and digital meetings. The survey instrument was translated based on the guidelines for the cultural adaptation of self-administrated measures. 
		                        		
		                        			Results:
		                        			The reliability of the questionnaire responses was measured by Cronbach’s alpha. The construct validity was checked through exploratory factor analysis followed by confirmatory factor analysis (CFA) to further assess the factor structure. CFA revealed that the model had excellent fit (root mean square error of approximation, 0.00; comparative fit index, 1.0; Tucker-Lewis index, 1; standardized root mean squared residual, 0.0). 
		                        		
		                        			Conclusions
		                        			The Arabic version of the teleworking questionnaire had high reliability and good validity in assessing experiences and perceptions toward teleworking. While the validated survey examined perceptions and experiences during COVID-19, its use can be extended to capture experiences and perceptions during different crises. 
		                        		
		                        		
		                        		
		                        	
2.Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality
Thanh N. NGUYEN ; Muhammad M. QURESHI ; Piers KLEIN ; Hiroshi YAMAGAMI ; Mohamad ABDALKADER ; Robert MIKULIK ; Anvitha SATHYA ; Ossama Yassin MANSOUR ; Anna CZLONKOWSKA ; Hannah LO ; Thalia S. FIELD ; Andreas CHARIDIMOU ; Soma BANERJEE ; Shadi YAGHI ; James E. SIEGLER ; Petra SEDOVA ; Joseph KWAN ; Diana Aguiar DE SOUSA ; Jelle DEMEESTERE ; Violiza INOA ; Setareh Salehi OMRAN ; Liqun ZHANG ; Patrik MICHEL ; Davide STRAMBO ; João Pedro MARTO ; Raul G. NOGUEIRA ; ; Espen Saxhaug KRISTOFFERSEN ; Georgios TSIVGOULIS ; Virginia Pujol LEREIS ; Alice MA ; Christian ENZINGER ; Thomas GATTRINGER ; Aminur RAHMAN ; Thomas BONNET ; Noémie LIGOT ; Sylvie DE RAEDT ; Robin LEMMENS ; Peter VANACKER ; Fenne VANDERVORST ; Adriana Bastos CONFORTO ; Raquel C.T. HIDALGO ; Daissy Liliana MORA CUERVO ; Luciana DE OLIVEIRA NEVES ; Isabelle LAMEIRINHAS DA SILVA ; Rodrigo Targa MARTÍNS ; Letícia C. REBELLO ; Igor Bessa SANTIAGO ; Teodora SADELAROVA ; Rosen KALPACHKI ; Filip ALEXIEV ; Elena Adela CORA ; Michael E. KELLY ; Lissa PEELING ; Aleksandra PIKULA ; Hui-Sheng CHEN ; Yimin CHEN ; Shuiquan YANG ; Marina ROJE BEDEKOVIC ; Martin ČABAL ; Dusan TENORA ; Petr FIBRICH ; Pavel DUŠEK ; Helena HLAVÁČOVÁ ; Emanuela HRABANOVSKA ; Lubomír JURÁK ; Jana KADLČÍKOVÁ ; Igor KARPOWICZ ; Lukáš KLEČKA ; Martin KOVÁŘ ; Jiří NEUMANN ; Hana PALOUŠKOVÁ ; Martin REISER ; Vladimir ROHAN ; Libor ŠIMŮNEK ; Ondreij SKODA ; Miroslav ŠKORŇA ; Martin ŠRÁMEK ; Nicolas DRENCK ; Khalid SOBH ; Emilie LESAINE ; Candice SABBEN ; Peggy REINER ; Francois ROUANET ; Daniel STRBIAN ; Stefan BOSKAMP ; Joshua MBROH ; Simon NAGEL ; Michael ROSENKRANZ ; Sven POLI ; Götz THOMALLA ; Theodoros KARAPANAYIOTIDES ; Ioanna KOUTROULOU ; Odysseas KARGIOTIS ; Lina PALAIODIMOU ; José Dominguo BARRIENTOS GUERRA ; Vikram HUDED ; Shashank NAGENDRA ; Chintan PRAJAPATI ; P.N. SYLAJA ; Achmad Firdaus SANI ; Abdoreza GHOREISHI ; Mehdi FARHOUDI ; Elyar SADEGHI HOKMABADI ; Mazyar HASHEMILAR ; Sergiu Ionut SABETAY ; Fadi RAHAL ; Maurizio ACAMPA ; Alessandro ADAMI ; Marco LONGONI ; Raffaele ORNELLO ; Leonardo RENIERI ; Michele ROMOLI ; Simona SACCO ; Andrea SALMAGGI ; Davide SANGALLI ; Andrea ZINI ; Kenichiro SAKAI ; Hiroki FUKUDA ; Kyohei FUJITA ; Hirotoshi IMAMURA ; Miyake KOSUKE ; Manabu SAKAGUCHI ; Kazutaka SONODA ; Yuji MATSUMARU ; Nobuyuki OHARA ; Seigo SHINDO ; Yohei TAKENOBU ; Takeshi YOSHIMOTO ; Kazunori TOYODA ; Takeshi UWATOKO ; Nobuyuki SAKAI ; Nobuaki YAMAMOTO ; Ryoo YAMAMOTO ; Yukako YAZAWA ; Yuri SUGIURA ; Jang-Hyun BAEK ; Si Baek LEE ; Kwon-Duk SEO ; Sung-Il SOHN ; Jin Soo LEE ; Anita Ante ARSOVSKA ; Chan Yong CHIEH ; Wan Asyraf WAN ZAIDI ; Wan Nur Nafisah WAN YAHYA ; Fernando GONGORA-RIVERA ; Manuel MARTINEZ-MARINO ; Adrian INFANTE-VALENZUELA ; Diederik DIPPEL ; Dianne H.K. VAN DAM-NOLEN ; Teddy Y. WU ; Martin PUNTER ; Tajudeen Temitayo ADEBAYO ; Abiodun H. BELLO ; Taofiki Ajao SUNMONU ; Kolawole Wasiu WAHAB ; Antje SUNDSETH ; Amal M. AL HASHMI ; Saima AHMAD ; Umair RASHID ; Liliana RODRIGUEZ-KADOTA ; Miguel Ángel VENCES ; Patrick Matic YALUNG ; Jon Stewart Hao DY ; Waldemar BROLA ; Aleksander DĘBIEC ; Malgorzata DOROBEK ; Michal Adam KARLINSKI ; Beata M. LABUZ-ROSZAK ; Anetta LASEK-BAL ; Halina SIENKIEWICZ-JAROSZ ; Jacek STASZEWSKI ; Piotr SOBOLEWSKI ; Marcin WIĄCEK ; Justyna ZIELINSKA-TUREK ; André Pinho ARAÚJO ; Mariana ROCHA ; Pedro CASTRO ; Patricia FERREIRA ; Ana Paiva NUNES ; Luísa FONSECA ; Teresa PINHO E MELO ; Miguel RODRIGUES ; M Luis SILVA ; Bogdan CIOPLEIAS ; Adela DIMITRIADE ; Cristian FALUP-PECURARIU ; May Adel HAMID ; Narayanaswamy VENKETASUBRAMANIAN ; Georgi KRASTEV ; Jozef HARING ; Oscar AYO-MARTIN ; Francisco HERNANDEZ-FERNANDEZ ; Jordi BLASCO ; Alejandro RODRÍGUEZ-VÁZQUEZ ; Antonio CRUZ-CULEBRAS ; Francisco MONICHE ; Joan MONTANER ; Soledad PEREZ-SANCHEZ ; María Jesús GARCÍA SÁNCHEZ ; Marta GUILLÁN RODRÍGUEZ ; Gianmarco BERNAVA ; Manuel BOLOGNESE ; Emmanuel CARRERA ; Anchalee CHUROJANA ; Ozlem AYKAC ; Atilla Özcan ÖZDEMIR ; Arsida BAJRAMI ; Songul SENADIM ; Syed I. HUSSAIN ; Seby JOHN ; Kailash KRISHNAN ; Robert LENTHALL ; Kaiz S. ASIF ; Kristine BELOW ; Jose BILLER ; Michael CHEN ; Alex CHEBL ; Marco COLASURDO ; Alexandra CZAP ; Adam H. DE HAVENON ; Sushrut DHARMADHIKARI ; Clifford J. ESKEY ; Mudassir FAROOQUI ; Steven K. FESKE ; Nitin GOYAL ; Kasey B. GRIMMETT ; Amy K. GUZIK ; Diogo C. HAUSSEN ; Majesta HOVINGH ; Dinesh JILLELA ; Peter T. KAN ; Rakesh KHATRI ; Naim N. KHOURY ; Nicole L. KILEY ; Murali K. KOLIKONDA ; Stephanie LARA ; Grace LI ; Italo LINFANTE ; Aaron I. LOOCHTAN ; Carlos D. LOPEZ ; Sarah LYCAN ; Shailesh S. MALE ; Fadi NAHAB ; Laith MAALI ; Hesham E. MASOUD ; Jiangyong MIN ; Santiago ORGETA-GUTIERREZ ; Ghada A. MOHAMED ; Mahmoud MOHAMMADEN ; Krishna NALLEBALLE ; Yazan RADAIDEH ; Pankajavalli RAMAKRISHNAN ; Bliss RAYO-TARANTO ; Diana M. ROJAS-SOTO ; Sean RULAND ; Alexis N. SIMPKINS ; Sunil A. SHETH ; Amy K. STAROSCIAK ; Nicholas E. TARLOV ; Robert A. TAYLOR ; Barbara VOETSCH ; Linda ZHANG ; Hai Quang DUONG ; Viet-Phuong DAO ; Huynh Vu LE ; Thong Nhu PHAM ; Mai Duy TON ; Anh Duc TRAN ; Osama O. ZAIDAT ; Paolo MACHI ; Elisabeth DIRREN ; Claudio RODRÍGUEZ FERNÁNDEZ ; Jorge ESCARTÍN LÓPEZ ; Jose Carlos FERNÁNDEZ FERRO ; Niloofar MOHAMMADZADEH ; Neil C. SURYADEVARA, MD ; Beatriz DE LA CRUZ FERNÁNDEZ ; Filipe BESSA ; Nina JANCAR ; Megan BRADY ; Dawn SCOZZARI
Journal of Stroke 2022;24(2):256-265
		                        		
		                        			 Background:
		                        			and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. 
		                        		
		                        			Methods:
		                        			We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). 
		                        		
		                        			Results:
		                        			There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths.  
		                        		
		                        			Conclusions
		                        			During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT. 
		                        		
		                        		
		                        		
		                        	
3.Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE)
Martin J. O’DONNELL ; Matthew MCQUEEN ; Allan SNIDERMAN ; Guillaume PARE ; Xingyu WANG ; Graeme J. HANKEY ; Sumathy RANGARAJAN ; Siu Lim CHIN ; Purnima RAO-MELACINI ; John FERGUSON ; Denis XAVIER ; Liu LISHENG ; Hongye ZHANG ; Prem PAIS ; Patricio LOPEZ-JARAMILLO ; Albertino DAMASCENO ; Peter LANGHORNE ; Annika ROSENGREN ; Antonio L. DANS ; Ahmed ELSAYED ; Alvaro AVEZUM ; Charles MONDO ; Conor JUDGE ; Hans-Christoph DIENER ; Danuta RYGLEWICZ ; Anna CZLONKOWSKA ; Nana POGOSOVA ; Christian WEIMAR ; Romana IQBAL ; Rafael DIAZ ; Khalid YUSOFF ; Afzalhussein YUSUFALI ; Aytekin OGUZ ; Ernesto PENAHERRERA ; Fernando LANAS ; Okechukwu S. OGAH ; Adesola OGUNNIYI ; Helle K. IVERSEN ; German MALAGA ; Zvonko RUMBOLDT ; Shahram OVEISGHARAN ; Fawaz AL HUSSAIN ; Yongchai NILANONT ; Salim YUSUF ;
Journal of Stroke 2022;24(2):224-235
		                        		
		                        			 Background:
		                        			and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. 
		                        		
		                        			Methods:
		                        			Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). 
		                        		
		                        			Results:
		                        			Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001).  
		                        		
		                        			Conclusions
		                        			The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk. 
		                        		
		                        		
		                        		
		                        	
4.A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms.
Muhammad ZUBAIR ; Ranjha KHAN ; Ao MA ; Uzma HAMEED ; Mazhar KHAN ; Tanveer ABBAS ; Riaz AHMAD ; Jian-Teng ZHOU ; Wasim SHAH ; Ansar HUSSAIN ; Nisar AHMED ; Ihsan KHAN ; Khalid KHAN ; Yuan-Wei ZHANG ; Huan ZHANG ; Li-Min WU ; Qing-Hua SHI
Asian Journal of Andrology 2022;24(3):255-259
		                        		
		                        			
		                        			Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
		                        		
		                        		
		                        		
		                        			Asthenozoospermia/pathology*
		                        			;
		                        		
		                        			Dyneins/genetics*
		                        			;
		                        		
		                        			Homozygote
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Microtubule-Associated Proteins
		                        			;
		                        		
		                        			Mutation
		                        			;
		                        		
		                        			Mutation, Missense
		                        			;
		                        		
		                        			Sperm Tail/metabolism*
		                        			
		                        		
		                        	
5. Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels
Rabia IQBAL ; Sohaib PEERZADA ; Sajid ALI ; Irfan HAMID ; Khalid Hussain JANBAZ ; Muhammad Furqan AKHTAR ; Ammara SALEEM ; Ali SHARIF ; Bushra AKHTAR ; Kashif SOHAIL
Asian Pacific Journal of Tropical Biomedicine 2021;11(5):214-221
		                        		
		                        			
		                        			 Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models. Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders. 
		                        		
		                        		
		                        		
		                        	
6.Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels
Iqbal RABIA ; Hamid IRFAN ; Janbaz Hussain KHALID ; Akhtar Furqan MUHAMMAD ; Saleem AMMARA ; Sharif ALI ; Peerzada SOHAIB ; Akhtar BUSHRA ; Sohail KASHIF ; Ali SAJID
Asian Pacific Journal of Tropical Biomedicine 2021;11(5):214-221
		                        		
		                        			
		                        			Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders.
		                        		
		                        		
		                        		
		                        	
7.Congenital hyperinsulinism: 2 case reports with different rare variants in ABCC8
Julie MOURON-HRYCIUK ; Sophie STOPPA-VAUCHER ; Kanetee BUSIAH ; Thérèse BOUTHORS ; Maria Christina ANTONIOU ; Eric JACOT ; Klaus BRUSGAARD ; Henrik Thybo CHRISTESEN ; Khalid HUSSAIN ; Andrew DWYER ; Matthias ROTH-KLEINER ; Michael HAUSCHILD
Annals of Pediatric Endocrinology & Metabolism 2021;26(1):60-65
		                        		
		                        			
		                        			Congenital hyperinsulinism (CHI) is a rare glucose metabolism disorder characterized by unregulated secretion of insulin that leads to hyperinsulinemic hypoglycemia (HH). Most cases are caused by mutations in the KATP-channel genes ABCC8 and KCNJ11. We report 2 patients that experienced severe HH from the first day of life. Patient 1 developed midgut volvulus after initiating diazoxide and required intestinal resection. He was subsequently managed with a high-dose octreotide and glucose-enriched diet. Consistent with diffuse type CHI by 18F-dihydroxyphenylalanine positron emission tomography-computed tomography, genetic testing revealed a homozygous ABCC8 variant, c.1801G>A, p.(Val601Ile). The rare variant was previously reported to be diazoxide-responsive, and the patient responded well to diazoxide monotherapy, with clinical remission at 2 years of age. Patient 2 responded to diazoxide with spontaneous clinical remission at 15 months of age. However, an oral glucose tolerance test at 7 years of age revealed hyperinsulinism. Genetic testing revealed that the proband and several seemingly healthy family members harbored a novel, heterozygous ABCC8 variant, c.1780T>C, p.(Ser594Pro). Genetic findings identified previously unrecognized HH in the proband’s mother. The proband’s uncle had been diagnosed with monogenic ABCC8-diabetes and was successfully transitioned from insulin to glibenclamide therapy. We report findings of intestinal malrotation and volvulus occurring 2 days after initiation of diazoxide treatment. We also report a novel, heterozygous ABCC8 variant in a family that exhibited cases of CHI in infancy and HH and monogenic diabetes in adult members. The cases demonstrate the importance and clinical utility of genetic analyses for informing and guiding treatment and care.
		                        		
		                        		
		                        		
		                        	
8.Determination of Bergenin in Different Parts of Bergenia ciliata using a Validated RP-HPLC Method
Ejaz ALI ; Khalid HUSSAIN ; Nadeem Irfan BUKHARI ; Najma ARSHAD ; Amjad HUSSAIN ; Nasir ABBAS ; Sohail ARSHAD ; Sajida PARVEEN ; Naureen SHEHZADI ; Shaista QAMAR ; Abida QAMAR
Natural Product Sciences 2021;27(1):54-59
		                        		
		                        			
		                        			Bergenia ciliata (Family: Saxifragaceae) is a folklore remedy for the treatment of various ailments in Asian countries. Bergenin (1) has been isolated as an active constituent in many studies, however, the amount of bergenin has not been determined in all parts of the plant. A simple RP-HPLC method was developed to determine the amount of bergenin in methanol extracts of leaves, rhizomes and roots of the plant. Separation was achieved on an Agilent Eclipse XDB-C18 column maintained at 25 o C using isocratic solvent system (water: methanol: acetic acid; 62.5:37:0.5 v/v/v) adjusted at pH 2 0 at a flow rate of 1.0 mL/min. and detected at 275 nm. Correlation coefficient (0.9952) showed linearity of concentration (5-200 μg/mL) and response. The values of LOD (0.00947 μg/mL) and LOQ (0.02869 μg/mL) indicated that method was sensitive. The recovery of bergenin was 99.99-100% indicating accuracy of method. The methanol extract of rhizomes contained higher amount of bergenin (19.4%) than roots (9.2%) and leaves (6.9%). It is concluded that methanol extract of rhizomes is a better source of bergenin than other parts of the plant. The findings are useful for standardization of bergenin containing extracts and herbal preparations.
		                        		
		                        		
		                        		
		                        	
9.Congenital hyperinsulinism: 2 case reports with different rare variants in ABCC8
Julie MOURON-HRYCIUK ; Sophie STOPPA-VAUCHER ; Kanetee BUSIAH ; Thérèse BOUTHORS ; Maria Christina ANTONIOU ; Eric JACOT ; Klaus BRUSGAARD ; Henrik Thybo CHRISTESEN ; Khalid HUSSAIN ; Andrew DWYER ; Matthias ROTH-KLEINER ; Michael HAUSCHILD
Annals of Pediatric Endocrinology & Metabolism 2021;26(1):60-65
		                        		
		                        			
		                        			Congenital hyperinsulinism (CHI) is a rare glucose metabolism disorder characterized by unregulated secretion of insulin that leads to hyperinsulinemic hypoglycemia (HH). Most cases are caused by mutations in the KATP-channel genes ABCC8 and KCNJ11. We report 2 patients that experienced severe HH from the first day of life. Patient 1 developed midgut volvulus after initiating diazoxide and required intestinal resection. He was subsequently managed with a high-dose octreotide and glucose-enriched diet. Consistent with diffuse type CHI by 18F-dihydroxyphenylalanine positron emission tomography-computed tomography, genetic testing revealed a homozygous ABCC8 variant, c.1801G>A, p.(Val601Ile). The rare variant was previously reported to be diazoxide-responsive, and the patient responded well to diazoxide monotherapy, with clinical remission at 2 years of age. Patient 2 responded to diazoxide with spontaneous clinical remission at 15 months of age. However, an oral glucose tolerance test at 7 years of age revealed hyperinsulinism. Genetic testing revealed that the proband and several seemingly healthy family members harbored a novel, heterozygous ABCC8 variant, c.1780T>C, p.(Ser594Pro). Genetic findings identified previously unrecognized HH in the proband’s mother. The proband’s uncle had been diagnosed with monogenic ABCC8-diabetes and was successfully transitioned from insulin to glibenclamide therapy. We report findings of intestinal malrotation and volvulus occurring 2 days after initiation of diazoxide treatment. We also report a novel, heterozygous ABCC8 variant in a family that exhibited cases of CHI in infancy and HH and monogenic diabetes in adult members. The cases demonstrate the importance and clinical utility of genetic analyses for informing and guiding treatment and care.
		                        		
		                        		
		                        		
		                        	
10.Determination of Bergenin in Different Parts of Bergenia ciliata using a Validated RP-HPLC Method
Ejaz ALI ; Khalid HUSSAIN ; Nadeem Irfan BUKHARI ; Najma ARSHAD ; Amjad HUSSAIN ; Nasir ABBAS ; Sohail ARSHAD ; Sajida PARVEEN ; Naureen SHEHZADI ; Shaista QAMAR ; Abida QAMAR
Natural Product Sciences 2021;27(1):54-59
		                        		
		                        			
		                        			Bergenia ciliata (Family: Saxifragaceae) is a folklore remedy for the treatment of various ailments in Asian countries. Bergenin (1) has been isolated as an active constituent in many studies, however, the amount of bergenin has not been determined in all parts of the plant. A simple RP-HPLC method was developed to determine the amount of bergenin in methanol extracts of leaves, rhizomes and roots of the plant. Separation was achieved on an Agilent Eclipse XDB-C18 column maintained at 25 o C using isocratic solvent system (water: methanol: acetic acid; 62.5:37:0.5 v/v/v) adjusted at pH 2 0 at a flow rate of 1.0 mL/min. and detected at 275 nm. Correlation coefficient (0.9952) showed linearity of concentration (5-200 μg/mL) and response. The values of LOD (0.00947 μg/mL) and LOQ (0.02869 μg/mL) indicated that method was sensitive. The recovery of bergenin was 99.99-100% indicating accuracy of method. The methanol extract of rhizomes contained higher amount of bergenin (19.4%) than roots (9.2%) and leaves (6.9%). It is concluded that methanol extract of rhizomes is a better source of bergenin than other parts of the plant. The findings are useful for standardization of bergenin containing extracts and herbal preparations.
		                        		
		                        		
		                        		
		                        	
            
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