bluuebunny/crossref_metadata_2025 huggingface dataset:
Global peak left atrial longitudinal strain assessed by transthoracic echocardiography is a good predictor of left atrial appendage thrombus in patients in sinus rhythm with heart failure and very low ejection fraction – an observational study
Authors: Kurzawski Jacek , Janion-Sadowska Agnieszka , Zandecki Lukasz , Piatek Lukasz , Koziel Dorota , Sadowski Marcin
Published: February 2020

Background

Peak left atrial longitudinal strain (PALS) can help identify left atrial appendage thrombus (LAAT) in patients with atrial fibrillation. Nevertheless, few studies have been performed in patients in sinus rhythm without established indications for anticoagulation but with increased risk of LAAT, such as heart failure (HF) with severe left ventricular systolic dysfunction patients. The primary aim of this study was to identify clinical and transthoracic echocardiography predictors of LAAT in HF patients with very low left ventricular ejection fraction and sinus rhythm. The secondary objective was to analyze frequencies and predictors of a composite clinical endpoint of death or hospitalization for ischemic stroke.

Methods

We included 63 patients with HF, left ventricular ejection fraction < 25%, sinus rhythm at presentation, no history of atrial fibrillation, and without any established indications for anticoagulation. We determined whether clinical and transthoracic echocardiography parameters, including left atrial strain analysis, predicted LAAT. Transesophageal echocardiography was performed in all patients. When LAAT was detected, anticoagulation was recommended. The participants were followed for a median of 28.6 months (range 4–40) to determine the composite endpoint.

Results

LAAT was found in 20 (31.7%) patients. Global PALS was the best independent predictor of LAAT in univariate and multivariate logistic regression analyses (Gini coefficient 0.65, area under the receiver-operating characteristic curve 0.83). A global PALS value below 8% was a good discriminator of LAAT presence (odds ratio 30.4, 95% CI 7.2–128, p <  0.001). During follow-up, 18 subjects (28.6%) reached the composite clinical endpoint. CHA2DS2-VASc score, use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers, and body surface area were significant predictors for the composite endpoint of death or hospitalization for ischemic stroke in the multivariate regression model.

Conclusions

LAAT was relatively common in our group of HF patients and PALS has shown prognostic potential in LAAT identification. Further research is needed to determine whether initiation of anticoagulation or additional screening supported by PALS measurements will improve clinical outcomes in these patients.
Clemastine improves hypomyelination in rats with hypoxic–ischemic brain injury by reducing microglia-derived IL-1β via P38 signaling pathway
Authors: Xie Di , Ge Xiaoli , Ma Yanli , Tang Jialong , Wang Yang , Zhu Yajie , Gao Chengjin , Pan Shuming
Published: February 2020

Background

Microglia activation is associated with the development of hypoxic–ischemic brain injury (HIBI). Neuroinflammation suppression might be a suitable therapeutic target in hypoxic oligodendrocyte injury. This study aims to determine whether clemastine can improve hypomyelination by suppressing the activated microglia and promoting the maturation of oligodendrocyte progenitor cells (OPCs) in HIBI.

Methods

A bilateral common carotid artery occlusion (BCCAO) rat model that received continuous intraperitoneal injection (1 mg/kg) for 14 days was employed to elaborate the neuroprotection effects of clemastine. Interleukin-1β (IL-1β), nod-like receptor protein 3 (NLRP3), histamine H1 receptor, and OPC differentiation levels in the corpus callosum were measured. Primary cultured OPCs and co-culture of microglia and OPCs were used to explore the link between microglia activation and hypomyelination. Data were evaluated by one-way ANOVA with Fisher’s protected least significant difference test.

Results

Clemastine treatment could reverse hypomyelination and restrain the upregulation of IL-1β and NLRP3 in the corpus callosum of BCCAO rats. Primary cultured OPCs treated with IL-1β showed failed maturation. However, clemastine could also reverse the OPC maturation arrest by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Co-culture of microglia and OPCs with oxygen glucose deprivation treatment exhibited IL-1β and NLRP3 upregulation. Clemastine could downregulate NLRP3 and IL-1β and reverse hypomyelination by inhibiting the p38 signaling pathway.

Conclusions

Clemastine could restrain microglia activation, improve axonal hypomyelination in BCCAO rats, and thus might be a viable strategy to inhibit hypomyelination in the corpus callosum of patients with HIBI.
Effects of inflammation on the kynurenine pathway in schizophrenia — a systematic review
Authors: Pedraz-Petrozzi Bruno , Elyamany Osama , Rummel Christoph , Mulert Christoph
Published: February 2020

Background

In the last decade, there has been growing evidence that an interaction exists between inflammation and the kynurenine pathway in schizophrenia. Additionally, many authors found microglial activation in cases of schizophrenia due to inflammatory mechanisms related mostly to an increase of pro-inflammatory cytokines. In order to gain new insights into the pathophysiology of schizophrenia, it is important to incorporate the latest published evidence concerning inflammatory mechanisms and kynurenine metabolism. This systematic review aims to collect reliable recent findings within the last decade supporting such a theory.

Methods

A structured search of electronic databases was conducted for publications between 2008 and 2018 to identify eligible studies investigating patients with schizophrenia/psychosis and the relationship between inflammation and kynurenine pathway. Applicable studies were systematically scored using the NIH Quality Assessment Tools. Two researchers independently extracted data on diagnosis (psychosis/schizophrenia), inflammation, and kynurenine/tryptophan metabolites.

Results

Ten eligible articles were identified where seven studies assessed blood samples and three assessed cerebrospinal fluid in schizophrenic patients.

Of these articles:

Four investigated the relationship between immunoglobulins and the kynurenine pathway and found correlations between IgA-mediated responses and levels of tryptophan metabolites (i.e., kynurenine pathway).

Five examined the correlation between cytokines and kynurenine metabolites where three showed a relationship between elevated IL-6, TNF-α concentrations, and the kynurenine pathway.

Only one study discovered correlations between IL-8 and the kynurenine pathway.

Two studies showed correlations with lower concentrations of IL-4 and the kynurenine pathway.

Moreover, this systematic review did not find a significant correlation between CRP (n = 1 study), IFN-γ (n = 3 studies), and the kynurenine pathway in schizophrenia.

Interpretation

These results emphasize how different inflammatory markers can unbalance the tryptophan/kynurenine pathway in schizophrenia. Several tryptophan/kynurenine pathway metabolites are produced which can, in turn, underlie different psychotic and cognitive symptoms via neurotransmission modulation. However, due to heterogeneity and the shortage of eligible articles, they do not robustly converge to the same findings. Hence, we recommend further studies with larger sample sizes to elucidate the possible interactions between the various markers, their blood vs. CSF ratios, and their correlation with schizophrenia symptoms.
Factors affecting cytological results of endoscopic ultrasound guided-fine needle aspiration during learning
Authors: Lai Jian-Han , Lin Hsiang-Hung , Lin Ching-Chung
Published: February 2020

Background

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a standard procedure used to obtain tissue samples for diagnosis of solid retroperitoneal tumours. However, this procedure demands high technical expertise and requires a strong learning curve. Our aim was to identify factors associated with false-negative EUS-FNA results during the learning for endoscopists.

Methods

Our retrospective analysis was based on the EUS-FNA specimens collected by two novice endoscopists in 200 patients with retroperitoneal lesions who had confirmed image- or tissue-based diagnoses of malignancy or benign lesions.

Results

In the first 40 performances endoscopists, the false-negative diagnostic rate of EUS-FNA was higher among patients with chronic pancreatitis than in patients without chronic pancreatitis. Patients who underwent FNA through the trans-duodenal puncture route also had lower success cytological diagnosis rate than through the trans-gastric puncture route. The rate of successful cytological diagnoses with EUS-FNA improved after 40 procedures and was not influenced by chronic pancreatitis presentation or difference puncture route.

Conclusion

Regarding the learning curve, more than 40 procedures were required to achieve a stable success rate of EUS-FNA. Chronic pancreatitis and trans-duodenal puncture route are the predictive factors for a false-negative FNA cytological result during learning.

Trial registration

This was a retrospective study.
Hybrid dysgenesis in Drosophila virilis results in clusters of mitotic recombination and loss-of-heterozygosity but leaves meiotic recombination unaltered
Authors: Hemmer Lucas W. , Dias Guilherme B. , Smith Brittny , Van Vaerenberghe Kelley , Howard Ashley , Bergman Casey M. , Blumenstiel Justin P.
Published: February 2020

Background

Transposable elements (TEs) are endogenous mutagens and their harmful effects are especially evident in syndromes of hybrid dysgenesis. InDrosophila virilis, hybrid dysgenesis is a syndrome of incomplete gonadal atrophy that occurs when males with multiple active TE families fertilize females that lack active copies of the same families. This has been demonstrated to cause the transposition of paternally inherited TE families, with gonadal atrophy driven by the death of germline stem cells. Because there are abundant, active TEs in the male inducer genome, that are not present in the female reactive genome, theD. virilissyndrome serves as an excellent model for understanding the effects of hybridization between individuals with asymmetric TE profiles.

Results

Using theD. virilissyndrome of hybrid dysgenesis as a model, we sought to determine how the landscape of germline recombination is affected by parental TE asymmetry. Using a genotyping-by-sequencing approach, we generated a high-resolution genetic map ofD. virilisand show that recombination rate and TE density are negatively correlated in this species. We then contrast recombination events in the germline of dysgenic versus non-dysgenic F1 females to show that the landscape of meiotic recombination is hardly perturbed during hybrid dysgenesis. In contrast, hybrid dysgenesis in the female germline increases transmission of chromosomes with mitotic recombination. Using a de novo PacBio assembly of theD. virilisinducer genome we show that clusters of mitotic recombination events in dysgenic females are associated with genomic regions with transposons implicated in hybrid dysgenesis.

Conclusions

Overall, we conclude that increased mitotic recombination is likely the result of early TE activation in dysgenic progeny, but a stable landscape of meiotic recombination indicates that either transposition is ameliorated in the adult female germline or that regulation of meiotic recombination is robust to ongoing transposition. These results indicate that the effects of parental TE asymmetry on recombination are likely sensitive to the timing of transposition.
A pilot study using environmental screening to determine the prevalence of Mycobacterium avium subspecies paratuberculosis (MAP) and antimicrobial resistance (AMR) in Irish cattle herds
Authors: Ramovic Elvira , Madigan Gillian , McDonnell Shannon , Griffin Denise , Bracken Elaine , NiGhallchoir Eadaoin , Quinless Emma , Galligan Aoife , Egan John , Prendergast Deirdre M.
Published: February 2020

Background

Dairy and beef cattle can be reservoirs of many pathogens, including Salmonella and Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne’s disease (JD). Farm environments may provide potential entry points for the transmission of infectious agents into the food chain. Antibiotics are used to treat a wide variety of infections on farms, and administration of antimicrobial agents to cattle is considered to be a driving factor for antimicrobial resistance (AMR). Control of JD and AMR are priority for animal health initiatives in Ireland. A national JD pilot programme was introduced by Animal Health Ireland in 2014, while the national action plan launched by Department of Health and Department of Agriculture, Food and Marine introduced in 2017 aims to improve the surveillance of AMR. The current investigation was undertaken as a pilot study to determine the proportion of herds positive for MAP, Salmonella species (Salmonella spp), commensal Escherichia coli (E. coli), Extended-spectrum beta-lactamase (ESBL) AmpC β-lactamase and carbapenemase-producing E. coli from 157 environmental faecal samples in Irish farms.

Results

MAP was detected in 10.2% of samples collected; on culture in 4 (4.9%) of the dairy herds and from 1 (1.3%) of the beef/suckler herds, and by PCR in 10 (12.3%) and 6 (7.9%) of these herds respectively. All culture positive herds were also positive by PCR. An additional 11 herds were positive by PCR only. Salmonella was not detected, while commensal E. coli were isolated from 70.7% of the samples (111/157) with 101 of these isolates shown to be fully susceptible to all antimicrobials tested. Of the 27 presumptive ESBL AmpC β-lactamase producing E. coli detected, one isolate was resistant to ten antimicrobials, nine isolates were resistant to nine antimicrobials, and four isolates were resistant to eight antimicrobials. Carbapenemase-producing E. coli were not isolated.

Conclusions

The results highlight the importance of monitoring farm environments for Johne’s disease. This disease is a growing concern for dairy and beef producers in Ireland, and sampling the farm environment may offer a useful means to rapidly screen for the presence of MAP. Non-pathogenic common enteric commensal and multiple-drug-resistant E. coli may contribute to AMR acting as a reservoir and transferring resistance to other species/pathogens in the environment.
Metabolic dependencies govern microbial syntrophies during methanogenesis in an anaerobic digestion ecosystem
Authors: Zhu Xinyu , Campanaro Stefano , Treu Laura , Seshadri Rekha , Ivanova Natalia , Kougias Panagiotis G. , Kyrpides Nikos , Angelidaki Irini
Published: February 2020

Methanogenesis, a biological process mediated by complex microbial communities, has attracted great attention due to its contribution to global warming and potential in biotechnological applications. The current study unveiled the core microbial methanogenic metabolisms in anaerobic vessel ecosystems by applying combined genome-centric metagenomics and metatranscriptomics. Here, we demonstrate that an enriched natural system, fueled only with acetate, could support a bacteria-dominated microbiota employing a multi-trophic methanogenic process. Moreover, significant changes, in terms of microbial structure and function, were recorded after the system was supplemented with additional H2. Methanosarcina thermophila, the predominant methanogen prior to H2 addition, simultaneously performed acetoclastic, hydrogenotrophic, and methylotrophic methanogenesis. The methanogenic pattern changed after the addition of H2, which immediately stimulated Methanomicrobia-activity and was followed by a slow enrichment of Methanobacteria members. Interestingly, the essential genes involved in the Wood-Ljungdahl pathway were not expressed in bacterial members. The high expression of a glycine cleavage system indicated the activation of alternative metabolic pathways for acetate metabolism, which were reconstructed in the most abundant bacterial genomes. Moreover, as evidenced by predicted auxotrophies, we propose that specific microbes of the community were forming symbiotic relationships, thus reducing the biosynthetic burden of individual members. These results provide new information that will facilitate future microbial ecology studies of interspecies competition and symbiosis in methanogenic niches.
A pipeline for targeted metagenomics of environmental bacteria
Authors: Grieb Anissa , Bowers Robert M. , Oggerin Monike , Goudeau Danielle , Lee Janey , Malmstrom Rex R. , Woyke Tanja , Fuchs Bernhard M.
Published: February 2020

Background

Metagenomics and single cell genomics provide a window into the genetic repertoire of yet uncultivated microorganisms, but both methods are usually taxonomically untargeted. The combination of fluorescence in situ hybridization (FISH) and fluorescence activated cell sorting (FACS) has the potential to enrich taxonomically well-defined clades for genomic analyses.

Methods

Cells hybridized with a taxon-specific FISH probe are enriched based on their fluorescence signal via flow cytometric cell sorting. A recently developed FISH procedure, the hybridization chain reaction (HCR)-FISH, provides the high signal intensities required for flow cytometric sorting while maintaining the integrity of the cellular DNA for subsequent genome sequencing. Sorted cells are subjected to shotgun sequencing, resulting in targeted metagenomes of low diversity.

Results

Pure cultures of different taxonomic groups were used to (1) adapt and optimize the HCR-FISH protocol and (2) assess the effects of various cell fixation methods on both the signal intensity for cell sorting and the quality of subsequent genome amplification and sequencing. Best results were obtained for ethanol-fixed cells in terms of both HCR-FISH signal intensity and genome assembly quality. Our newly developed pipeline was successfully applied to a marine plankton sample from the North Sea yielding good quality metagenome assembled genomes from a yet uncultivated flavobacterial clade.

Conclusions

With the developed pipeline, targeted metagenomes at various taxonomic levels can be efficiently retrieved from environmental samples. The resulting metagenome assembled genomes allow for the description of yet uncharacterized microbial clades.
A thermo-elastoplastic self-consistent homogenization method for inter-granular plasticity with application to thermal ratcheting of TATB
Authors: Bennett Kane C. , Zecevic Miroslav , Luscher Darby J. , Lebensohn Ricardo A.
Published: February 2020

A novel thermo-elastoplastic self-consistent homogenization model for granular materials that exhibit inter-granular plasticity is presented. The model, TEPSCA, is made possible by identifying a new inter-granular plastic Eshelby-like tensor. A micromechanical model of interfacial yielding between grains of a Mohr–Coulomb type is provided, which is relatable to the description of imperfect interfaces within the paradigm of self-consistent homogenization. The local grain constitutive laws are consistent with the description of an interphase layer comprised of local pore volume between grains, such that inelastic inter-particle displacements are directly relatable to changes in bulk porosity, i.e., dilation. The model was developed for the purpose of modeling thermally induced plasticity—the phenomenon known as thermal ratcheting or “ratchet growth”—of composites made from the high explosive triaminotrinitrobenzene (TATB). Model simulations are compared to ratchet growth measurements during cyclic thermal loading of a TATB pellet under stress-free conditions.
Enriched homogenized model for viscoelastic plane wave propagation in periodic layered composites
Authors: Tan Swee Hong , Poh Leong Hien
Published: February 2020

An enriched homogenized model is developed based on a proposed homogenization strategy, to describe the wave propagation behaviour through periodic layered composites. The intrinsic parameters characterising the micro-inertia effect and non-local interactions are defined transparently in terms of the constituent materials’ properties and volume fractions. The framework starts with the introduction of an additional kinematic field to characterise the displacement of the stiff layer, before setting up macro kinematic fields to account for the average deformation of the constituent materials within a segmented unit cell. Relationships between these macro average strain fields are determined based on suitable micro-mechanical arguments. The Hill–Mandel condition is next applied to translate the energy statements from micro to macro. A system of coupled governing equations of motion is finally extracted naturally at the macro level via Hamilton’s Principle. Through a series of benchmark examples, it is shown that the proposed model exhibits excellent predictive capabilities over a broad range of loading frequencies.
Top online luxury apparel and accessories retailers: what are they doing right?
Authors: Mu Wenzhao , Lennon Sharron J. , Liu Wenqiao
Published: February 2020

Many luxury firms have successfully adopted online sales and online sales growth has outperformed offline sales growth. As online luxury sales continue to grow, service expectations in digital and instore channels are also expected to grow. To add to the research literature, the top performing 46 luxury apparel and accessories websites identified in the Luxury e-Commerce Report from Internet Retailer were content analyzed to determine the state of the art in top performing luxury retail websites in providing needed information (international customer service attributes). Those top performing websites were then compared to 44 randomly selected similar websites on the same attributes to determine how the two groups of websites compared in terms of international customer service attributes. Although top performing luxury retail websites are providing important customer service information that facilitates online purchasing, there is room for improvement. In comparing the two groups of online luxury merchants, each group had strengths and weaknesses. Overall, merchants performed at a suboptimal level on provision of many customer service attributes, need improvement on others, and performed well on a few attributes. These luxury fashion online retailers are at an early stage in providing important customer service attributes on their websites.
The association of urinary uric acid excretion with ambulatory blood pressure values in patients with chronic kidney disease
Authors: Xu Ying , Zhou Xun , Zheng Yuqi , Guan Haochen , Fu Chensheng , Xiao Jing , Ye Zhibin
Published: February 2020

Background

To analyze the association between hypertension and urinary uric acid excretion in patients with chronic kidney disease (CKD).

Methods

We screened 87 patients who had been admitted at the Dept of Nephrology, Huadong hospital between April 2017 to April 2019 who had completed 24-h ambulatory blood pressure monitoring and retained 24-h urine biochemical test specimens, thirty adult patients (age ≤ 65 years) with CKD 1–2 stages were recruited in the study. Pearson’s correlation analysis and multiple linear regression analysis were used to study the correlation of urinary uric acid excretion with ambulatory blood pressure values and the association of morning mean diastolic pressure (mMDP), night mean diastolic pressure (nMDP) and CV of dMSP (coefficient of variation of day mean systolic pressure) with fractional excretion of uric acid (FEua) and uric acid clearance rate (Cur). Independent T test was used to compare the differences of blood pressure values in FEua1 (FEua< 6.0%) and FEua2 (FEua≥6.0%) or Cur1 (Cur < 6.2 ml/min/1.73 m2) and Cur2 (Cur ≥ 6.2 ml/min/1.73m2) groups according to the median of FEua or Cur, respectively.

Results

After adjusting for confounding factors, multiple linear regression analysis showed that FEua was positively associated with the mMDP and nMDP, Cur was positively associated with CV of dMSP. Levels of mMDP and nMDP in FEua1 group was lower than that in FEua2 group (both P < 0.05), level of CV of dMSP in Cur2 group were higher than that in Cur1 group (P < 0.01).

Conclusions

We demonstrated that there is a positive correlation of FEua with morning and night mean diastolic pressure separately and Cur is positively related to CV of dMSP in CKD population. Monitoring the trend of urinary uric acid, may have a role in the early detection for hypertension or relative risks in the population of CKD.
Painful myokymia after surgery in a patient with Isaacs’ syndrome: a case report
Authors: Okutani Hiroai , Okano Yukari , Hirose Munetaka
Published: February 2020

Background

Isaacs’ syndrome is a peripheral nerve hyperexcitability syndrome and rare acquired channel disease. The symptoms (myokymia, neuromyotonia, and muscle spasm) emerge even during sleep. This report describes the anesthetic management, especially neuromuscular blocking drugs and postoperative pain, in a case of Isaacs’ syndrome.

Case presentation

A 63-year-old woman with Isaacs’ syndrome underwent elective laparoscopic distal gastrectomy under general anesthesia without epidural anesthesia. She received double filtration plasmapheresis four times to alleviate symptoms before surgery. To avoid a prolonged neuromuscular blockade, we performed total intravenous anesthesia and titrated muscle relaxant with neuromuscular monitoring. Anesthetic management was performed without any problems. However, pain management after surgery proved difficult as she experienced severe pain due to myokymia.

Conclusions

Despite attempts to minimize symptoms, severe postoperative pain associated with myokymia occurred. Continuous regional anesthesia should be considered to treat pain from abnormal discharge in the central nervous system in Isaacs’ syndrome.
Molecular Basis of CYP19A1 Deficiency in a 46,XX Patient With R550W Mutation in POR: Expanding the PORD Phenotype
Authors: Parween Shaheena , Fernández-Cancio Mónica , Benito-Sanz Sara , Camats Núria , Rojas Velazquez Maria Natalia , López-Siguero Juan-Pedro , Udhane Sameer S , Kagawa Norio , Flück Christa E , Audí Laura , Pandey Amit V
Published: February 2020

Context

Mutations in cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We report a novel R550W mutation in POR identified in a 46,XX patient with signs of aromatase deficiency.

Objective

Analysis of aromatase deficiency from the R550W mutation in POR.

Design, setting, and patient

Both the child and the mother had signs of virilization. Ultrasound revealed the presence of uterus and ovaries. No defects in CYP19A1 were found, but further analysis with a targeted Disorders of Sexual Development NGS panel (DSDSeq.V1, 111 genes) on a NextSeq (Illumina) platform in Madrid and Barcelona, Spain, revealed compound heterozygous mutations c.73_74delCT/p.L25FfsTer93 and c.1648C > T/p.R550W in POR. Wild-type and R550W POR were produced as recombinant proteins and tested with multiple cytochrome P450 enzymes at University Children’s Hospital, Bern, Switzerland.

Main outcome measure and Results

POR-R550W showed 41% of the WT activity in cytochrome c and 7.7% activity for reduction of MTT. Assays of CYP19A1 showed a severe loss of activity, and CYP17A1 as well as CYP21A2 activities were also lost by more than 95%. Loss of CYP2C9, CYP2C19, and CYP3A4 activities was observed for the R550W-POR. Predicted adverse effect on aromatase activity as well as a reduction in binding of NADPH was confirmed.

Conclusions

Pathological effects due to POR-R550W were identified, expanding the knowledge of molecular pathways associated with aromatase deficiency. Screening of the POR gene may provide a diagnosis in CAH without defects in genes for steroid metabolizing enzymes.
Loss-of-Function Variants in TBC1D32 Underlie Syndromic Hypopituitarism
Authors: Hietamäki Johanna , Gregory Louise C , Ayoub Sandy , Iivonen Anna-Pauliina , Vaaralahti Kirsi , Liu Xiaonan , Brandstack Nina , Buckton Andrew J , Laine Tiina , Känsäkoski Johanna , Hero Matti , Miettinen Päivi J , Varjosalo Markku , Wakeling Emma , Dattani Mehul T , Raivio Taneli
Published: February 2020

Context

Congenital pituitary hormone deficiencies with syndromic phenotypes and/or familial occurrence suggest genetic hypopituitarism; however, in many such patients the underlying molecular basis of the disease remains unknown.

Objective

To describe patients with syndromic hypopituitarism due to biallelic loss-of-function variants in TBC1D32, a gene implicated in Sonic Hedgehog (Shh) signaling.

Setting

Referral center.

Patients

A Finnish family of 2 siblings with panhypopituitarism, absent anterior pituitary, and mild craniofacial dysmorphism, and a Pakistani family with a proband with growth hormone deficiency, anterior pituitary hypoplasia, and developmental delay.

Interventions

The patients were investigated by whole genome sequencing. Expression profiling of TBC1D32 in human fetal brain was performed through in situ hybridization. Stable and dynamic protein-protein interaction partners of TBC1D32 were investigated in HEK cells followed by mass spectrometry analyses.

Main Outcome Measures

Genetic and phenotypic features of patients with biallelic loss-of-function mutations in TBC1D32.

Results

The Finnish patients harboured compound heterozygous loss-of-function variants (c.1165_1166dup p.(Gln390Phefs*32) and c.2151del p.(Lys717Asnfs*29)) in TBC1D32; the Pakistani proband carried a known pathogenic homozygous TBC1D32 splice-site variant c.1372 + 1G > A p.(Arg411_Gly458del), as did a fetus with a cleft lip and partial intestinal malrotation from a terminated pregnancy within the same pedigree. TBC1D32 was expressed in the developing hypothalamus, Rathke’s pouch, and areas of the hindbrain. TBC1D32 interacted with proteins implicated in cilium assembly, Shh signaling, and brain development.

Conclusions

Biallelic TBC1D32 variants underlie syndromic hypopituitarism, and the underlying mechanism may be via disrupted Shh signaling.
Outcome of management of brain abscess in children
Authors: Khan Ikram Ullah , Latif Abdul , Ashraf Muhammad , Chishti Muhammad Kashif , Sadiq Sadia
Published: February 2020

Objective: To find out the outcome of management of brain abscess in children.

Methods: This is prospective observational study conducted in the Department of Paediatric Neurosurgery at Children’s Hospital and Institute of Child Health, Multan from July 2014 to June 2017. Children up to the age of 14 years suffering from brain abscess were admitted. After taking clinical history, general and systemic physical examination and necessary investigations, abscess was evacuated and abscess wall excised after performing craniotomy. Data was collected on a predesigned performa. Results were analyzed and compared with national and international literature through statistical package for social sciences (SPSS-20).

Results: Twenty five patients up to 14 years of age were included. Seventeen (68%) were male and eight (32%) female. Fever and vomiting were present in all 25 (100%) patients. Paranasal sinusitis was predisposing causative factor in 9(36%) followed by otitis media in 7 (28%). Abscess was present in frontal lobe in 9 (36%), temporoparietal region in 8 (32%), posterior fossa in 5 (20%) and multiple abscesses in 3 (12%). Craniotomy was performed, pus evacuated and abscess wall excised in all 25 (100%) patients. Three (12%) patients expired.

Conclusion: Incidence of brain abscess can be decreased by treatment of its predisposing causes as sinusitis and otitis media. Small abscess less than 2cm can be treated with antibiotics. Complete evacuation of pus and excision of abscess wall after performing craniotomy along with appropriate antibiotics is gold standard management of brain abscess in children.

doi: https://doi.org/10.12669/pjms.36.3.1087

How to cite this:Khan IU, Latif A, Ashraf M, Chishti MK, Sadiq S. Outcome of management of brain abscess in children. Pak J Med Sci. 2020;36(3):306-309. doi: https://doi.org/10.12669/pjms.36.3.1087

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Role of Methyl Prednisolone in Longitudinal Extensive Transverse Myelitis (LETM) in Children
Authors: Ashfaq Muhammad Azeem , Javed Iram , Arshad Muhammad , Yaseen Muhammad Rizwan
Published: February 2020

Objective: The role of methyl prednisolone in longitudinal extensive transverse myelitis in children is not completely discovered in developing country like Pakistan. So this is the first study which aimed to evaluate the efficacy of methyl prednisolone in longitudinal extensive transverse myelitis in children.

Methods: This is quasi experimental hospital based descriptive prospective study. The data was collected from 34 children admitted in Paediatric Neurology department through Outpatient/emergency department in Children’s Hospital and the Institute of Child Health, Lahore for period of one year from January 2018 to December 2018. The children full filling the inclusion criteria were observed before and after giving injection methyl prednisolone 30mg/kg/dose (maximum dose one Gram irrespective of the body weight) once daily for five days in the form of intravenous infusion.

Results: Complete recovery was seen in 41.2% while 58.8% showed partial recovery. The correlation of response to treatment (recovery) with gender, area of spinal cord involvement, muscle power and autonomic dysfunction is found at significance level of five percent according to Chi square test.

Conclusion: Early consideration and administration of methyl prednisolone in longitudinally extensive transverse myelitis in children can be beneficial and can help to reduce the morbidity.

doi: https://doi.org/10.12669/pjms.36.3.1232

How to cite this:Ashfaq MA, Javed I, Arshad M, Yaseen MR. Role of Methyl Prednisolone in Longitudinal Extensive Transverse Myelitis (LETM) in Children. Pak J Med Sci. 2020;36(3):451-455. doi: https://doi.org/10.12669/pjms.36.3.1232

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Prevalence of Vitamin-D deficiency is related to severity of liver damage in Hepatitis-C patients
Authors: Falak Sadia , Aftab Lubna , Saeed Muhammad , Islam Aftab
Published: February 2020

Objective: Serum Vitamin-D plays pivotal role in inflammatory and infectious diseases; among them liver infections are more distinct. This study was aimed to determine Vitamin-D status in HCV-infected patients and healthy controls in Faisalabad, Pakistan.

Methods: We performed randomized cross-sectional study of 74 individuals from 20th August, 2017 to 20th February 2018 at The University of Faisalabad and Dar us Shifa Clinic, Faisalabad. Fifty-one patients were hepatitis C RNA-PCR positive (22 compensated cirrhotic and 29 decompensated cirrhotic patients). In addition, 23 subjects without liver disease were recruited as healthy control. HCV RNA–PCR was performed by ARTUS ® HCV QS-RGQ V1. Vitamin-D levels were measured by chemiluminescence. SPSS version 20 was used for statistical analysis.

Results: The mean level of Vitamin-D was significantly lower in HCV patients in compensated and decompensated cirrhotic patients (26.85 ng/mL & 20.65 ng/mL respectively) as compared to healthy controls (30.41 ng/mL). This study showed sub optimal level of Vitamin-D in 76.5% of HCV patients. Vitamin-D insufficiency (21-29 ng/mL) as prevalent among healthy individuals (47.8%) as well as in HCV patients (39.2%) (P < 0.001). In addition, Vitamin-D levels showed inverse relationship with more severe conditions of liver disease as 55.2% of decompensated cirrhosis patients were sufferer of Vitamin-D deficiency as compared to 13.6% deficiency of Vitamin-D in compensated cirrhotic group (P <0.0001).

Conclusion: Suboptimal levels of Vitamin-D (deficiency or insufficiency) are prevalent in patients having hepatitis C infection as compared to healthy controls. Deficiency of Vitamin-D was directly associated with severity of disease.

doi: https://doi.org/10.12669/pjms.36.3.1490

How to cite this:Falak S, Aftab L, Saeed M, Islam A. Prevalence of Vitamin-D deficiency is related to severity of liver damage in Hepatitis-C patients. Pak J Med Sci. 2020;36(3):445-450. doi: https://doi.org/10.12669/pjms.36.3.1490

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Association of lamina cribrosa morphometry with retinal nerve fiber layer loss and visual field defects in primary open angle glaucoma
Authors: Naz Ayesha Saba , Qamar Aisha , Haque Sama Ul , Zaman Yawar , Faheem Faisal
Published: February 2020

Objectives: To calculate the anterior lamina cribrosa depth (ALCD) and lamina cribrosa thickness (LCT) in primary open angle glaucoma (POAG) patients and controls and to correlate lamina cribrosa (LC) parameters to retinal nerve fiber layer thickness (RNFLT) and visual field (VF) defects.

Methods: The study was conducted from November 2018 to March 2019. A total of 60 correspondents (30 cases and 30 controls) were assessed for general ophthalmological investigations including intraocular pressure (IOP), axial length AXL, ophthalmoscopy, visual field (VF) testing and spectral domain ocular computed tomography (SDOCT).

Results: The mean age of subjects was 62 years (Cases 67.30±1.2, controls 57.32±1.1) with more male participants. Intraocular pressure [IOP (19.85 ±1.4)], AXL (22.85 ± 1.6), VF defects (8.30 ± 4.5), RNFLT (72.58 ± 13.2) and LCT (162.51 ± 64.62) were statistically significant in POAG patients as compared to the controls.

Conclusion: A thinner LC in POAG correlated significantly with the RNFLT and VF defects. LC anatomical parameters can be estimated with precision using SDOCT with enhanced depth imaging (EDI).

doi: https://doi.org/10.12669/pjms.36.3.1553

How to cite this:Naz AS, Qamar A, Sama-Ul-Haque, Zaman Y, Faheem F. Association of lamina cribrosa morphometry with retinal nerve fiber layer loss and visual field defects in primary open angle glaucoma. Pak J Med Sci. 2020;36(3):521-525. doi: https://doi.org/10.12669/pjms.36.3.1553

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Stress and coping strategies for parenting children with hearing impairment and autism
Authors: Ishtiaq Naima , Mumtaz Nazia , Saqulain Ghulam
Published: February 2020

Objectives: To determine the level of stress experienced and coping strategies used by parents of hearing impaired and autistic children.

Methods: Using non-probability convenience sampling this cross sectional study recruited n =200 parents of hearing impaired (HI) and 100 parents of autistic children, of either gender, aged 20 to 60 years. Samples were recruited from Special Education Institutes of Islamabad and Rawalpindi, over a period of six months, from October 2018 to March 2019 and conducted at Isra Institute of Rehabilitation Sciences, Islamabad. Basic demographical sheet, Parental Stress Scale and Coping Strategies Inventory were used for data collection. Statistical analysis was done using SPSS 21.

Results: In parents of hearing impaired the mean parental stress score was 47.44±12.85 and commonest coping strategy was problem focused engagement (26.03) followed by problem focused dis-engagement (24.25). In the autistic group the mean parental stress score was 48.92+11.22 with problem focused engagement being the most frequently used strategy (27.4) followed by emotion focused strategy.

Conclusion: Different level of stress experienced by parents of autistic and hearing impaired children which is statistically significant and they employed different coping strategies.

doi: https://doi.org/10.12669/pjms.36.3.1766

How to cite this:Ishtiaq N, Mumtaz N, Saqulain G. Stress and coping strategies for parenting children with hearing impairment and autism. Pak J Med Sci. 2020;36(3):538-543. doi: https://doi.org/10.12669/pjms.36.3.1766

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Influence of fractional carbon-dioxide laser in comparison to ErCr-YSGG on the dentin bond integrity of bioactive materials
Authors: Al Jeaidi Zaid A.
Published: February 2020

Objective: The aim was to assess the influence of Er,Cr:YSGG laser (ECL) and fractional carbon dioxide laser (FCL) on the shear bond strength (SBS) and microleakage of bioactive restorative material to dentin.

Methods: The study was performed in King Saud university in the month of June-July 2019. One hundred and twenty permanent teeth were vertically placed in acrylic resin. Based on the type of surface treatment regime (n=40), samples were divided into three groups. Group-I samples were surface conditioned with total etch and rinse (TE); Group-2 samples were surface treated with Er,Cr:YSGG laser (ECL) and Group-3 specimens were conditioned with fractional carbon dioxide laser (FCL). Surface treatment of dentin was followed by type of bulk fill resin (BFR) application. Tetric-N-Ceram was bonded to dentin conditioned with TE (n=20), FCL (n=20) and ECL (n=20). Similarly, bioactive material (BAM) was also bonded to conditioned surface (n=60). Samples (n=10) among each group were placed in a Universal testing machine. For microleakage testing 5 pairs of samples from each group (n=10) were placed in solution of 2% methylene blue for 24h Fracture analysis was performed using stereomicroscope at 40x magnification. Descriptive statistics i.e., means and standard for SBS and microleakage were compared using analysis of variance (ANOVA) and Tukey’s post hoc test at a significance level of (p < 0.05)

Results: The highest SBS scores were displayed by TE-BFR (Bulk filled resin) (19.21 ± 0.925 Mpa) and the lowest shear bond scores were presented by FCL-BFR (11.06±1.611 Mpa). The lowest microleakage scores were exhibited by group ECL-BFR (24.11±13.01nm). Similarly, the highest microleakage score was displayed in group FCL-BAM (42.18±16.32 nm). Admixed failure was pertinent in groups conditioned by ECL. Moreover, groups conditioned with FCL adhesive type of failure was found in abundance.

Conclusions: ECL has a potential to be used as an alternate to total etch and rinse for conditioning of dentin when bonded to bioactive materials.

doi: https://doi.org/10.12669/pjms.36.3.1819

How to cite this:Al-Jeaidi Z. Influence of fractional carbon-dioxide laser in comparison to ErCr-YSGG on the dentin bond integrity of bioactive materials. Pak J Med Sci. 2020;36(3):526-531. doi: https://doi.org/10.12669/pjms.36.3.1819

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cranial CT scan evaluation of morphological variations and location of pterion in Pakistani male population for lateral neurosurgical approach
Authors: Rafi Aisha , Sayeed Sana , Anwar Muhammad Idrees
Published: February 2020

Objective: To determine the morphological variations and location of pterion in Pakistani male population.

Methods: This retrospective observational study was carried out in the Department of Radiology, Shifa International Hospital from December 2018 to June 2019. The sample size was calculated by Open Epi web-based calculator. Fifty-three cranial CT scans with slice thickness of 0.5mm; consecutive scans of males were randomly selected. The patients with no craniofacial fracture and ages from 25 to 45 years were included. The dataset was obtained from Toshiba Aquilion One, 360-slice MDCT. The images were imported into the imaging software PACS (WFM), and analyzed in maximum intensity projection mode with three dimensional multiplanar reconstruction viewers. Measurements were taken in lateral projections of skull in Frankfurt plane, as horizontal and vertical distance from the posterolateral margin of frontozygomatic suture to center of pterion. Vertical distance from the superior border of zygomaticotemporal arch to the center of pterion. The morphological types were also recognized.

Results: The type of pterion on right side was 94.3% sphenoparietal 5.6% epipteric whereas left side was (90.5%) sphenoparietal (3.7%) epipteric, (3.7%) stellate type, (1.8%) frontotemporal type. The mean horizontal and vertical frontozygomatic measurements on right side were 2.23±0.22cm and 1.25±0.219 cm respectively. The same measurements on the left side were 2.27-±0.25 cm and 1.226-±0.22 cm respectively. The mean zygomaticotemporal measurements on the right and left sides were 3.45±0.29cm and 3.44±0.25 cm respectively. The mean distance on right and left side of skull was statistically insignificant.

Conclusion: The study provides useful data for position and location of pterion for safe neurosurgical procedures via pterion. Moreover, the knowledge about different morphological types of pterion help the radiologist to differentiate between a fracture line and normal morphological variety.

doi: https://doi.org/10.12669/pjms.36.3.2003

How to cite this:Rafi A, Sayeed S, Anwar MI. Cranial CT scan evaluation of morphological variations and location of pterion in Pakistani male population for lateral neurosurgical approach. Pak J Med Sci. 2020;36(3):310-315. doi: https://doi.org/10.12669/pjms.36.3.2003

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Prognostic markers in Chronic Lymphocytic Leukaemia - A flow cytometric analysis
Authors: Haq Hala , Uddin Nasir , Khan Saleem Ahmed , Ghaffar Sunia
Published: February 2020

Objective: To find out the frequency of ZAP-70, CD38 and CD49d in patients diagnosed with CLL in our population.

Methods: This is a cross sectional study conducted in Army Medical College in collaboration with Armed Forces Institute of Pathology and Military Hospital Rawalpindi from 1st January 2018 to 30th November 2018. Permission from Institutional Ethical Committee was obtained. Blood samples were collected by non-probability consecutive sampling technique and analyzed for blood counts and flow cytometry was done for ZAP-70, CD38 and CD49d. Manufacturer’s instructions for the kits were strictly followed.

Results: Fifty-one newly diagnosed patients with CLL were studied for the prognostic markers in CLL. CD 38 was expressed in 25(49%) and CD49d in 21(41.2%). ZAP-70 expression was not detected in our series of patients.

Conclusion: We conclude that CD38 and CD49d expression was detected in almost half of the patients of CLL in our series. CD49d showed statistically positive correlation with CD38, showing that it is a more pragmatic choice for reliable prognostication of CLL along with CD38.

doi: https://doi.org/10.12669/pjms.36.3.541

How to cite this:Haq H, Uddin N, Khan SA, Sunia Ghaffar4. Prognostic markers in Chronic Lymphocytic Leukaemia - A flow cytometric analysis. Pak J Med Sci. 2020;36(3):338-343. doi: https://doi.org/10.12669/pjms.36.3.541

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.