bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co‐administration of morphine and levamisole increases death risk, produces neutropenia and modifies antinociception in mice
Authors: Ruiz‐Quiñonez Ana K. , Espinosa‐Riquer Zyanya P. , Carranza‐Aguilar César J. , Browne Thom , Cruz Silvia L. 
Published: March 2022

AbstractLevamisole is a veterinary anthelmintic drug and a common adulterant of misused drugs. This study analyses the lethal, antinociceptive and haematological effects produced by acute or repeated levamisole administration by itself or combined with morphine. Independent groups of male Swiss Webster mice were i.p. injected with 100 mg/kg morphine, 31.6 mg/kg levamisole (lethal doses at 10%, LD10) or the same doses combined. Naloxone pretreatment (10 mg/kg, i.p.) prevented morphine‐induced death, as did 2.5 mg/kg, i.p. mecamylamine with levamisole. Co‐administration of levamisole and morphine (Lvm + Mor) increased lethality from 10% to 80%. This augmented effect was prevented by 30 mg/kg, i.p. naloxone and reduced with 10 mg/kg naloxone plus 2.5 mg/kg, i.p. mecamylamine. In independent groups of mice, 17.7 mg/kg, i.p. levamisole antagonized the acute morphine's antinociceptive effect evaluated in the tail‐flick test. Repeated 17.7 mg/kg levamisole administration (2×/day/3 weeks) did not affect tolerance development to morphine (10 mg/kg, 3×/day/1 week). Blood samples obtained from mice repeatedly treated with levamisole showed leukopenia and neutropenia. Morphine also produced neutropenia, increased erythrocyte count and other related parameters (e.g. haemoglobin). Lvm + Mor had similar effects on leukocyte and neutrophil counts to those seen with levamisole only, but no erythrocyte‐related alterations were evident. Blood chemistry analysis did not indicate liver damage but suggested some degree of electrolyte balance impairment. In conclusion, Lvm + Mor increased death risk, altered morphine‐induced antinociceptive effects and produced haematologic abnormalities. The importance of studying combinations of drugs of abuse lies in the fact that drug users frequently combine drugs, which are commonly adulterated.
Linking restoration to the IUCN red list for ecosystems: A case study of how we might track the Earth's ecosystems
Authors: Tierney David A. 
Published: March 2022

AbstractGlobally, ecosystems are in decline and a capacity to track this decline and the progress of ecosystem restoration at this scale is critical. The IUCN Red List for Ecosystems (RLE) is the accepted standard for global ecosystem risk assessments and potentially could be used to track progress of ecosystem restoration. Ecosystem restoration progress to date has been assessed by a diversity of techniques that do not provide a coherent link to risk identified in RLE assessments. This study assesses the potential of the RLE as a benchmark for tracking recovery for an ecosystem. This is demonstrated using a case study ecosystem with complex and challenging restoration requirements. Box Gum Woodlands (BGW) in eastern Australia are critically endangered but occur across a large geographic area, often as small remnants on private land. RLE assessments were used to assess the extent of restoration required and if key altered ecological processes relating to soil properties, fragmentation and climate change must also be mitigated. This assessment clarified the scale of work required, the importance of private land conservation and a range of other factors (soil status; fragmentation pattern; climate change) critical to successful restoration. It is concluded that the RLE can provide a powerful benchmark for restoration goals, but an important aspect of its use is a capacity to manage uncertainty.
Single‐centre survey of women reflecting on recent experiences and preferences of oral intake during labour
Authors: McDermott Laura , Pelecanos Anita , Krepska Amy , de Jersey Susan , Sekar Renuka , Mao Derek , Lee Geraldine , Blackie Annika , Eley Victoria 
Published: March 2022

BackgroundConsensus‐based recommendations guiding oral intake during labour are lacking.AimsWe surveyed women at a tertiary women’s hospital about preferences for and experiences of oral intake during labour, gastrointestinal symptoms during labour and recalled advice about oral intake.Materials and methodsWomen who experienced labour completed a postpartum survey with responses as free text, yes‐no questions and five‐point Likert scales. We identified demographic data and risk factors for surgical or anaesthetic intervention at delivery from medical records. We summarised free text comments using conventional content analysis.ResultsOne hundred and forty‐nine women completed the survey (47% response rate). Their mean (SD) age was 31 (four) years, birthing at median gestation of 39 weeks (interquartile range: 38‐40). One hundred and twenty‐two (83%) and 44 (30%) women strongly agreed or agreed they felt like drinking and eating respectively during labour. Ninety women (61%) reported nausea and 47 women (32%) reported vomiting in labour. Forty‐one women (28%) did not receive advice on oral intake during labour. Maternal risk factors for surgical intervention were identified in 72 (48%) women and fetal risk factors in 27 (18%) women. Thirty‐one women (21%) delivered by emergency caesarean section.ConclusionPregnant women received variable advice regarding oral intake during labour, from variable sources. Most women felt like drinking but not eating during labour. Guidelines on oral intake in labour may be beneficial to women, balancing the preferences of women with risks of surgical intervention.
Toward transmural healing: Sonographic healing is associated with improved long‐term outcomes in patients with Crohn’s disease
Authors: Vaughan Rose , Tjandra Douglas , Patwardhan Ashwin , Mingos Nicholas , Gibson Robert , Boussioutas Alex , Ardalan Zaid , Al‐Ani Aysha , Gibson Peter R. , Christensen Britt 
Published: March 2022

AbstractBackground and AimsTransmural healing has emerged as a treatment target in Crohn’s disease (CD). We investigated whether transmural healing assessed with intestinal ultrasound (IUS) is associated with improved clinical outcomes in patients with CD in clinical remission.MethodsPatients with CD in clinical remission at baseline (HBI <4) having IUS between August 2017 and June 2020 with at least 6‐months’ follow‐up were retrospectively studied. Time to medication escalation, corticosteroid use and CD‐related hospitalisation or surgery were compared by the presence or absence of sonographic healing, defined as bowel wall thickness ≤3 mm without hyperemia on color Doppler, inflammatory fat, or disrupted bowel wall stratification. Factors associated with survival were analyzed by Kaplan–Meier analysis using Cox proportional‐hazard model.ResultsOf 202 consecutive patients (50% male), sonographic inflammation was present in 61%. During median follow‐up of 19 (IQR 13–27) months, medication escalation occurred in 52%, corticosteroid use in 23%, hospitalisation in 21%, and CD‐related surgery in 13%. Sonographic healing was significantly associated with a reduced risk of medication escalation (p = 0.0018), corticosteroid use (p = 0.0247), hospitalisation (p = 0.0102), and surgery (p = 0.083). On multivariable analysis, sonographic healing was significantly associated with an increased odds of medication escalation‐free survival (hazard ratio [HR]:1.94; 95% CI 1.23–3.06; p = 0.004) and corticosteroid‐free survival (HR:2.41; 95% CI 1.24–4.67; p = 0.009), but not with hospitalisation or surgery.ConclusionIn patients with CD in clinical remission, sonographic healing is associated with improved clinical outcomes. Further studies are needed to determine whether sonographic healing should be a treatment target.
Intraoperative visualization of urethra using illuminating catheter in laparoscopy‐assisted anorectoplasty for imperforated anus—A novel and safe technique for preventing urethral injury
Authors: Onishi Shun , Muto Mitsuru , Harumatsu Toshio , Murakami Masakazu , Kedoin Chihiro , Matsui Mayu , Sugita Koshiro , Yano Keisuke , Yamada Koji , Yamada Waka , Matsukubo Makoto , Kaji Tatsuru , Ieiri Satoshi 
Published: March 2022

AbstractPurposeIn this study, we used a near‐infrared ray catheter (NIRC) to visualize the urethral line. We herein report our intraoperative visualization technique of the urethra using an illuminating catheter in laparoscopy‐assisted anorectoplasty (LAARP) for imperforated anus.Patient and surgical techniqueA 3.0‐kg term male neonate with anorectal malformation was delivered. An invertogram revealed the type as intermediate. Transverse colostomy was performed at the left upper abdomen. A recto‐bulbar urethral fistula (RBUF) was diagnosed via distal colostogram and voiding cystourethrogram. LAARP was planned at 6 months of age. We performed the operation with four trocars. A 45° 5‐mm scope was used to clearly view the deep pelvic space. Before starting rectal dissection, a 6‐Fr pig‐tail‐type NIRC was inserted through the external opening of the urethra to visualize the urethra during the laparoscopic procedure. The catheter tip was placed in the bladder, and excretion of urine was maintained through the NIRC during the procedures. While dissecting the deep pelvic space between the posterior wall of the urethra and anterior wall of the rectum, the exact line of the urethra was clearly confirmed by overlay images of the NIRC. The RBUF was dissected safely using this innovative image‐guided technique. Anoplasty was performed between the rectal stump and perineal skin. The postoperative course was uneventful. Oral intake was started on postoperative day 1. Postoperative dynamic urography showed no complications.ConclusionAn NIRC is useful for detecting the urethra during LAARP.
Development and metamorphic loss of the musculature in larvae of the nudibranch Phestilla sibogae: A functional ontogeny
Authors: Croll Roger P. , Hadfield Michael G. 
Published: March 2022

AbstractDevelopmental programmes for many marine invertebrates include the assembly of muscular systems appropriate to the functions of swimming and feeding in pelagic larvae. Upon metamorphosis, that musculature is often radically re‐organized to meet very different demands of post‐larval life. To investigate the development and fate of musculature in the nudibranch Phestilla sibogae, embryos, larvae and metamorphosing stages were fixed, labelled with phalloidin and examined with confocal microscopy. The resultant images revealed the sequential development of both large retractor muscles and numerous finer muscles that allow the larva to manipulate the velum, foot and operculum. Observations of living specimens at the same stages as those fixed for microscopy revealed the actions of the muscles as they developed. During metamorphosis, muscles with shell attachments disintegrate as the larva transforms into a shell‐less juvenile. Notably, the massive velar, pedal and opercular retractor muscles disappear during metamorphosis in a sequence that corresponds to their loss of function. Other muscles, however, that appear to be important to the embryo and free‐swimming larva persist into juvenile life. The comprehensive and detailed observations of the musculature presented here provide a solid foundation for comparisons with other species with different phylogenies and life histories.
Asparaginase encapsulated in erythrocytes as second‐line treatment in hypersensitive patients with acute lymphoblastic leukaemia
Authors: Lynggaard Line Stensig , Vaitkeviciene Goda , Langenskiöld Cecilia , Lehmann Anne Kristine , Lähteenmäki Päivi M. , Lepik Kristi , El Hariry Iman , Schmiegelow Kjeld , Albertsen Birgitte Klug 
Published: March 2022

SummaryAsparaginase is essential in treating acute lymphoblastic leukaemia (ALL). Asparaginase‐related hypersensitivity causes treatment discontinuation, which is associated with decreased event‐free survival. To continue asparaginase treatment after hypersensitivity, a formulation of asparaginase encapsulated in erythrocytes (eryaspase) was developed. In NOR‐GRASPALL 2016 (NCT03267030) the safety and efficacy of eryaspase was evaluated in 55 patients (aged 1–45 years; median: 6.1 years) with non‐high‐risk ALL and hypersensitivity to asparaginase conjugated with polyethylene glycol (PEG‐asparaginase). Eryaspase (150 u/kg) was scheduled to complete the intended course of asparaginase (1–7 doses) in two Nordic/Baltic treatment protocols. Forty‐nine (96.1%) patients had asparaginase enzyme activity (AEA) ≥100 iu/l 14 ± 2 days after the first eryaspase infusion [median AEA 511 iu/l; interquartile range (IQR), 291–780], whereas six of nine (66.7%) patients had AEA ≥100 iu/l 14 ± 2 days after the fourth infusion (median AEA 932 iu/l; IQR, 496–163). The mean terminal half‐life of eryaspase following the first infusion was 15.3 ± 15.5 days. Few asparaginase‐related adverse events were reported; five patients (9.1%) developed clinical allergy associated with enzyme inactivation. Replacement therapy was successfully completed in 50 patients (90.9%). Eryaspase was well tolerated, and most patients had AEA levels above the therapeutic target after the first infusion. The half‐life of eryaspase confirmed that a 2‐week schedule is appropriate.
Inhibition of human recombinant T‐type calcium channels by phytocannabinoids in vitro
Authors: Mirlohi Somayeh , Bladen Chris , Santiago Marina J. , Arnold Jonathon C. , McGregor Iain , Connor Mark 
Published: March 2022

Background and PurposeT‐type Ca channels (ICa) regulate neuronal excitability and contribute to neurotransmitter release. The phytocannabinoids Δ9‐tetrahydrocannabinol and cannabidiol effectively modulate T‐type ICa, but effects of other biologically active phytocannabinoids on these channels are unknown. We thus investigated the modulation of T‐type ICa by low abundance phytocannabinoids.Experimental ApproachA fluorometric (fluorescence imaging plate reader [FLIPR]) assay was used to investigate modulation of human T‐type ICa (CaV3.1, 3.2 and 3.3) stably expressed in FlpIn‐TREx HEK293 cells. The biophysical effects of some compounds were examined using whole‐cell patch clamp recordings.Key ResultsIn the FLIPR assay, all 11 phytocannabinoids tested modulated T‐type ICa, with most inhibiting CaV3.1 and CaV3.2 more effectively than CaV3.3. Cannabigerolic acid was the most potent inhibitor of CaV3.1 (pIC50 6.1 ± 0.6) and CaV3.2 (pIC50 6.4 ± 0.4); in all cases, phytocannabinoid acids were more potent than their corresponding neutral forms. In patch clamp recordings, cannabigerolic acid inhibited CaV3.1 and 3.2 with similar potency to the FLIPR assay; the inhibition was associated with significant hyperpolarizing shift in activation and steady‐state inactivation of these channels. In contrast, cannabidiol, cannabidivarin, and cannabigerol only affected channel inactivation.Conclusion and ImplicationsModulation of T‐type calcium channels is a common property of phytocannabinoids, which all increase steady‐state inactivation at physiological membrane potentials, with some also affecting channel activation. Thus, T‐type ICa may be a common site of action for phytocannabinoids, and the diverse actions of phytocannabinoids on channel gating may provide insight into structural requirement for selective T‐type ICa modulators.
Familial cold autoinflammatory syndrome and multiple sclerosis
Authors: Ali Syed Basharat , Chaudhuri Debajyoti , Field Deborah , Hissaria Pravin 
Published: March 2022

AbstractBackgroundCryopyrin‐associated periodic syndrome (CAPS) is an autoinflammatory disorder with a spectrum ranging from the milder familial cold auto‐inflammatory syndrome (FCAS) phenotype to the more severe Muckle–Wells Syndrome. Although headaches are the most common neurological symptoms, neuroinflammatory diseases such as multiple sclerosis (MS) have only been reported in the more severe phenotypes.Case PresentationWe describe a 43‐year‐old male diagnosed with relapse‐remitting MS who developed cold‐induced arthralgias and urticaria. He initially presented with facial numbness and arthralgias in his late teenage years, and brain magnetic resonance imaging (MRI) demonstrated multiple lesions with periventricular white matter extension. Oligoclonal bands were detected in the cerebrospinal fluid (CSF). Symptoms gradually improved, and a decade later he presented with numbness at upper limbs and tongue. Brain and spine MRI showed new lesions, but CSF was unremarkable. He was started on interferon β‐1a with symptomatic improvement until another flare around 13 years later. Treatment was changed to dimethyl fumarate. During this hospitalization, urticaria was problematic and particularly associated with cold temperatures. This raised suspicion for possible CAPS and subsequently confirmed with an A439V mutation in the NLRP3 gene, consistent with FCAS. Anakinra was started but was not tolerated because of localized reactions despite desensitization. His serum amyloid A was mildly elevated at 9 mg/L (reference range 0–6). He remains stable from a neurological perspective, including imaging, and continues dimethyl fumarate.ConclusionsTo date, FCAS and possible association with MS has not been described. The case raises challenges in the diagnosis of concurrent disease processes. It also highlights that neurological sequelae should be considered in all spectrums of CAPS, and distinctions with MS should be made where possible.
De novo heterozygous variants in KIF5B cause kyphomelic dysplasia
Authors: Itai Toshiyuki , Wang Zheng , Nishimura Gen , Ohashi Hirofumi , Guo Long , Wakano Yasuhiro , Sugiura Takahiro , Hayakawa Hiromi , Okada Mayumi , Saisu Takashi , Kitta Ayana , Doi Hiroshi , Kurosawa Kenji , Hotta Yoshihiro , Hosono Katsuhiro , Sato Miho , Shimizu Kenji , Takikawa Kazuharu , Watanabe Seiji , Ikeda Naho , Suzuki Mitsuyoshi , Fujita Atsushi , Uchiyama Yuri , Tsuchida Naomi , Miyatake Satoko , Miyake Noriko , Matsumoto Naomichi , Ikegawa Shiro 
Published: March 2022

AbstractKyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled. We performed whole‐exome sequencing and evaluated the pathogenicity of the identified variants. All individuals had de novo heterozygous variants in KIF5B encoding kinesin‐1 heavy chain: two with c.272A>G:p.(Lys91Arg), one with c.584C>A:p.(Thr195Lys), and the other with c.701G>T:p.(Gly234Val). All variants involved conserved amino acids in or close to the ATPase activity‐related motifs in the catalytic motor domain of the KIF5B protein. All individuals had sharp angulation of the femora and humeri, distinctive facial features, and neonatal respiratory distress. Short stature was observed in three individuals. Three developed postnatal osteoporosis with subsequent fractures, two showed brachycephaly, and two were diagnosed with optic atrophy. Our findings suggest that heterozygous KIF5B deleterious variants cause a specific form of kyphomelic dysplasia. Furthermore, alterations in kinesins cause various symptoms known as kinesinopathies, and our findings also extend the phenotypic spectrum of kinesinopathies.
Lithium attenuates blood–brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β‐catenin signaling‐dependent mechanism in mice
Authors: Song Dengpan , Ji Ya‐Bin , Huang Xiao‐Wen , Ma Yin‐Zhong , Fang Cheng , Qiu Lin‐Hui , Tan Xi‐Xi , Chen Yi‐Man , Wang Sheng‐Nan , Chang Junlei , Guo Fuyou 
Published: March 2022

AbstractBackgroundVasogenic cerebral edema resulting from blood–brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation of endothelial Wnt/β‐catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate Wnt/β‐catenin signaling.MethodsWe evaluated the protective effect of lithium on the BBB in a mouse model of collagenase IV‐induced ICH. Furthermore, we assessed the effect and dependency of lithium on Wnt/β‐catenin signaling in mice with endothelial deletion of the Wnt7 coactivator Gpr124.ResultsLithium treatment (3 mmol/kg) significantly decreased the hematoma volume (11.15 ± 3.89 mm3 vs. 19.97 ± 3.20 mm3 in vehicle controls, p = 0.0016) and improved the neurological outcomes of mice following ICH. Importantly, lithium significantly increased the BBB integrity, as evidenced by reductions in the levels of brain edema (p = 0.0312), Evans blue leakage (p = 0.0261), and blood IgG extravasation (p = 0.0009) into brain tissue around the hematoma. Mechanistically, lithium upregulated the activity of endothelial Wnt/β‐catenin signaling in mice and increased the levels of tight junction proteins (occludin, claudin‐5 and ZO‐1). Furthermore, the protective effect of lithium on cerebral damage and BBB integrity was abolished in endothelial Gpr124 knockout mice, suggesting that its protective effect on BBB function was mainly dependent on Gpr124‐mediated endothelial Wnt/β‐catenin signaling.ConclusionOur findings indicate that lithium may serve as a therapeutic candidate for treating BBB breakdown and brain edema following ICH.
Does pre‐operative counselling of the donor improve immediate and short‐term outcomes after living liver donation? – A review of the literature and expert panel recommendations
Authors: Adams Megan A. , Andacoglu Oya , Crouch Cara E. , de Santibañes Martin , Jackson Whitney E. , Jalal Arif , Montasser Iman F. , Rubman Susan , Spiro Michael , Raptis Dimitri Aristotle , Miller Charles , Pomfret Elizabeth ,   the ERAS4OLT.org Working Group
Published: March 2022

AbstractBackgroundThere is some evidence in the literature to suggest that pre‐operative counselling improves pain scores postoperatively. However, it is unclear whether pre‐operative counselling of the donor improves immediate and short‐term outcomes after living liver donation.ObjectivesThis systematic review aimed to investigate the available quality of evidence (QOE) of pre‐operative counselling for living donors on short term outcomes, provide expert opinion, grade recommendations and identify relevant components for Enhanced Recovery after Surgery (ERAS) protocols.Data SourcesOvid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.MethodsSystematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Endpoints were defined by the WHOQOL‐BREF scale: physical health, psychological, social relationships, and environment. PROSPERO ID: CRD42021260677.ResultsScreening of 452 records and full texts led to 12 articles matching inclusion criteria, of which one was a randomized controlled trial (RCT), and 11 were observational retrospective cohort studies. A total of 933 individuals undergoing donor hepatectomy were included, of whom only 90 received dedicated perioperative ERAS protocols. Donors that received pre‐operative counselling had fewer physical symptoms post donation, lower rates of fatigue, lower rates of pain, shorter recovery times and fewer unexpected medical problems, and less anxiety post donation. Female donors had higher affective and adverse effects scores, and 50% of donors reported adverse effects to analgesia that interfered with functional activity. Receiving information about analgesic options increased perception of care among donors.ConclusionsProviding comprehensive pre‐operative counselling to living liver donors is associated with improved short‐term outcomes after donation (QOE; moderate to low I Grade of Recommendation; Strong).