bluuebunny/crossref_metadata_2025 huggingface dataset:
Levosimendan in the light of the results of the recent randomized controlled trials: an expert opinion paper
Authors: Cholley Bernard , Levy Bruno , Fellahi Jean-Luc , Longrois Dan , Amour Julien , Ouattara Alexandre , Mebazaa Alexandre
Published: November 2019

Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.

Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.

Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.
Development of clinically relevant in vivo metastasis models using human bone discs and breast cancer patient-derived xenografts
Authors: Lefley Diane , Howard Faith , Arshad Fawaz , Bradbury Steven , Brown Hannah , Tulotta Claudia , Eyre Rachel , Alférez Denis , Wilkinson J. Mark , Holen Ingunn , Clarke Robert B. , Ottewell Penelope
Published: November 2019

Background

Late-stage breast cancer preferentially metastasises to bone; despite advances in targeted therapies, this condition remains incurable. The lack of clinically relevant models for studying breast cancer metastasis to a human bone microenvironment has stunted the development of effective treatments for this condition. To address this problem, we have developed humanised mouse models in which breast cancer patient-derived xenografts (PDXs) metastasise to human bone implants with low variability and high frequency.

Methods

To model the human bone environment, bone discs from femoral heads of patients undergoing hip replacement surgery were implanted subcutaneously into NOD/SCID mice. For metastasis studies, 7 patient-derived xenograft tumours (PDX: BB3RC32, ER+ PR+ HER2−; BB2RC08, ER+ PR+ ER2−; BB6RC37, ER− PR− HER2− and BB6RC39, ER+ PR+ HER2+), MDA-MB-231-luc2, T47D-luc2 or MCF7-Luc2 cells were injected into the 4th mammary ducts and metastases monitored by luciferase imaging and confirmed on histological sections. Bone integrity, viability and vascularisation were assessed by uCT, calcein uptake and histomorphometry. Expression profiling of genes/proteins during different stages of metastasis were assessed by whole genome Affymetrix array, real-time PCR and immunohistochemistry. Importance of IL-1 was confirmed following anakinra treatment.

Results

Implantation of femoral bone provided a metabolically active, human-specific site for tumour cells to metastasise to. After 4 weeks, bone implants were re-vascularised and demonstrated active bone remodelling (as evidenced by the presence of osteoclasts, osteoblasts and calcein uptake). Restricting bone implants to the use of subchondral bone and introduction of cancer cells via intraductal injection maximised metastasis to human bone implants. MDA-MB-231 cells specifically metastasised to human bone (70% metastases) whereas T47D, MCF7, BB3RC32, BB2RC08, and BB6RC37 cells metastasised to both human bone and mouse bones. Importantly, human bone was the preferred metastatic site especially from ER+ PDX (100% metastasis human bone compared with 20–75% to mouse bone), whereas ER-ve PDX developed metastases in 20% of human and 20% of mouse bone. Breast cancer cells underwent a series of molecular changes as they progressed from primary tumours to bone metastasis including altered expression of IL-1B, IL-1R1, S100A4, CTSK, SPP1 and RANK. Inhibiting IL-1B signalling significantly reduced bone metastasis.

Conclusions

Our reliable and clinically relevant humanised mouse models provide significant advancements in modelling of breast cancer bone metastasis.
Associations between certolizumab pegol serum levels, anti-drug antibodies and treatment response in patients with inflammatory joint diseases: data from the NOR-DMARD study
Authors: Gehin Johanna Elin , Goll Guro Løvik , Warren David John , Syversen Silje Watterdal , Sexton Joseph , Strand Eldri Kveine , Kvien Tore Kristian , Bolstad Nils , Lie Elisabeth
Published: November 2019

Objectives

To identify a therapeutic target interval for certolizumab pegol drug levels and examine the influence of anti-drug antibodies in patients with inflammatory joint diseases.

Methods

Certolizumab pegol and anti-drug antibody levels were measured in serum samples collected after 3 months of certolizumab pegol treatment in 268 patients with inflammatory joint diseases (116 axial spondyloarthritis, 91 rheumatoid arthritis and 61 psoriatic arthritis) in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score Clinically important improvement in axial spondyloarthritis, European League Against Rheumatism good/moderate response in rheumatoid arthritis, and improvement in 28-joint Disease Activity Score of ≥ 0.6 in PsA. Serum drug levels and anti-drug antibodies were analysed using automated in-house assays.

Results

Certolizumab pegol serum levels varied considerably between individuals (median (IQR) 32.9 (17.3–43.9) mg/L). Certolizumab pegol level ≥ 20 mg/L was associated with treatment response for the total inflammatory joint disease population, with odds ratio (OR) 2.3 (95% CI 1.2–4.5, P = 0.01) and OR 1.9 (95% CI 1.0–3.5, P = 0.05) after 3 and 6 months of treatment, respectively. For individual diagnoses, this association was most consistent for axial spondyloarthritis, with OR 3.4 (95% CI 1.0–11.1, P < 0.05) and OR 3.3 (95% CI 1.0–10.8, P < 0.05), respectively. Certolizumab pegol level > 40 mg/L was not associated with any additional benefit for any of the diagnoses. Anti-drug antibodies were detected in 6.1% (19/310) of samples and were associated with low certolizumab pegol levels (P < 0.01).

Conclusions

Serum certolizumab pegol levels 20–40 mg/L were associated with treatment response in inflammatory joint diseases. Our study is the first to show this association in axial spondyloarthritis and psoriatic arthritis patients. The results suggest a possible benefit of therapeutic drug monitoring in patients with inflammatory joint disease on certolizumab pegol treatment.

Trial registration

NCT01581294, April 2012.
An alarming rise of non-albicans Candida species and uncommon yeasts in the clinical samples; a combination of various molecular techniques for identification of etiologic agents
Authors: Taei Monireh , Chadeganipour Mostafa , Mohammadi Rasoul
Published: November 2019

Objective

Yeasts are unicellular microorganisms may cause systemic infection in immunocompromised patients. The aim of this study was to identify yeast strains isolated from clinical specimens using molecular techniques.

Results

A total of 202 yeast strains isolated from 341 clinical samples between February 2017 and May 2019. All clinical isolates were identified using phenotypic and molecular tests including PCR–RFLP, duplex-PCR, multiplex-PCR, and PCR-sequencing. The most yeast fungal isolates were obtained from urine (66.8%), nail (9.4%), skin lesion (7.9%), bronchoalveolar lavage (5.9%), and blood (3.9%). One hundred and twenty-one Candida species were identified as non-albicans versus 76 Candida albicans. Trichosporon asahii, and Pichia terricola were uncommon non-Candida yeasts isolated from urine samples. For the first time, we isolated P. terricola as etiological agent of urinary tract infection in a pregnant female. Since Candida species show different levels of resistance to antifungal agents, precise identification of clinical isolates is critical for better treatment of infection.
Advanced primary urethral cancer: a case report
Authors: Chen Huan , Zou Li Li , Dong Chuan Jiang , Li Tao , Dong Zi Qiang
Published: November 2019

Background

Primary urethral cancer is exceedingly rare, resulting in a limitation in clinicians’ experience, and an accurate diagnosis is often delayed due to the non-specific clinical presentation. Here, we present this case report to show the treatment of a patient with primary urethral cancer. Our patient was diagnosed as having primary urethral cancer in the First Clinical Hospital of Yichang by cystoscopy and biopsy. Due to her age, poor physical tolerance, and economic condition, she refused radical operation. Since there is no definite guideline for the treatment process of primary urethral cancer in clinics, operation methods and postoperative adjuvant treatments vary in different hospitals, leading to diverse prognostic effects.

Case presentation

An 88-year-old Asian woman had difficulty in urinating for more than 6 months and the syndrome was aggravated for 1 month. She chose a relatively conservative treatment plan: primary tumor resection combined with bladder perfusion chemotherapy. Postoperative pathology revealed “urethra” high-grade urothelial carcinoma (sarcoma-like variants) with extensive necrosis. After treatment with intravesical chemotherapeutic drug (hydroxycamptothecin 40 mg), she was eventually released from our hospital in a stable condition. Postoperation follow-up was performed to observe to what extent this conservative treatment plan improved the quality of life and overall survival time of our patient.

Conclusions

She needed radical resection according to the actual situation. However, her age restricted her tolerance to general anesthesia; relatively conservative treatment options are available to ensure a high quality of life. The treatment of primary tumor resection combined with bladder perfusion chemotherapy is feasible. This case highlights the importance of the dissemination of new cases and optimizing primary urethral cancer diagnosis to obtain an effective treatment.
Diabetes drugs for nonalcoholic fatty liver disease: a systematic review
Authors: Blazina Ian , Selph Shelley
Published: November 2019

Background

Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis, strategies to ameliorate fatty liver often target these related diseases. We sought to determine if any medications approved by the US Food and Drug Administration to treat diabetes are helpful in reducing weight and improving steatohepatitis in patients with NAFLD.

Methods

We conducted a systematic review of published and unpublished studies evaluating the comparative effectiveness and harms of diabetes medications for the treatment of NAFLD. We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials through 3rd quarter, 2019 using terms for included drugs and indications.

Results

We screened 1591 citations and included 18 trials of diabetes drugs to treat NAFLD. Studies of metformin found no difference from placebo in steatosis, fibrosis, NAFLD activity score, or resolution of NASH. While weight and glucose control were improved with metformin, it did not substantially impact liver disease. Studies of pioglitazone in NASH patients found benefits in liver function, liver fat, and NASH resolution, though significant increases in weight may be cause for concern. Evidence for other thiazolinediones was more limited and had somewhat mixed results, but findings were generally consistent with those for pioglitazone: liver fat and function and glucose measures improved, but weight also increased. We found some evidence that liraglutide improves liver fat, liver function, and HbA1c and is effective at resolving NASH and reducing weight. Exenatide performed less well but also resulted in significant reductions in liver fat and weight.

Conclusions

Consistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.
Sites of synchronous distant metastases and prognosis in prostate cancer patients with bone metastases at initial diagnosis: a population‐based study of 16,643 patients
Authors: Zhao Feng , Wang Jili , Chen Meiqin , Chen Danni , Ye Sunyi , Li Xinke , Chen Xin , Ren Guoping , Yan Senxiang
Published: November 2019

Background

Bone is a preferential site for prostate cancer (PCa) metastasis. However, sites of synchronous distant metastases in PCa patients with bone metastases at initial diagnosis and their impacts on prognosis are still unclear, limiting our ability to better stratify and treat the patients. In this study, we examined the sites of synchronous extra‐skeletal metastases in de novo PCa patients with bone metastases and their associated prognoses.

Methods

In total, 16,643 de novo PCa patients with bone metastases from the SEER database were included. After stratification of metastatic sites (bone, lung, liver, and brain) and treatment modalities, overall survival (OS) and independent predictors of OS, were analyzed.

Results

Lung was the most frequent site of synchronous metastases, followed by liver, while brain metastases were relatively uncommon. Patients with bone‐only metastases showed the longest mean survival time (35.87 months, p < 0.001), followed by patients with bone and lung metastases (30.74 months, p < 0.001). Patients with bone and liver metastases had the shortest mean survival time (17.39 months, p < 0.001). Age > 70 years, unmarried status, high tumor grade, prostate‐specific antigen (PSA) > 50 ng/ml, and Gleason score ≥ 8 were associated with poor OS (all p < 0.01). Asian or Pacific Islander ethnic background was associated with a favorable OS (all p < 0.01). Chemotherapy improved OS in patients without brain metastases (all p < 0.05). For patients with bone‐only metastases, radical prostatectomy (RP) (HR, 0.339; 95% CI 0.231–0.495; p < 0.001), brachytherapy (BT) (HR, 0.567; 95% CI 0.388–0.829; p = 0.003), and chemotherapy (HR, 0.850; 95% CI 0.781–0.924; p < 0.001) were associated with prolonged OS.

Conclusions

Age, race, tumor grade, PSA, Gleason score, sites of synchronous extra‐skeletal metastases, as well as treatment modalities affected OS in newly diagnosed PCa patients with bone metastases. Synchronous liver metastases were associated with poor OS. Chemotherapy improved OS in patients without brain metastases. RP and BT improved OS in patients with bone‐only metastases. Further investigation is warranted to validate these findings.
Sodium valproate induced acute pancreatitis in a bipolar disorder patient: a case report
Authors: Huang Wanli , Ren Xin , Shen Fang , Xing Baoping
Published: November 2019

Background

Sodium valproate is one of the most widely used antiepileptics and mood stabilizers. However, this drug may induce acute pancreatitis. Few cases have been reported so far, mainly on the pediatric patients who underwent antiepileptic treatment. Hereby, we present a case of bipolar disorder with sodium valproate-induced acute pancreatitis.

Case presentation

The patient is a 54-year-old Chinese male. He was diagnosed with bipolar disorder for more than 39 years. Since the first onset of the disease, he had several relapses. The patient had had sodium valproate to stabilize mood swings for a year before the occurrence of acute pancreatitis. But he did vomit once during the inpatient care period. Then he was referred to another hospital following a notably high level of amylase. The results of computed tomography demonstrated an increased pancreatic volume and swollen peripancreatic fat tissue. As a result, the patient was diagnosed with acute pancreatitis. Unlike other cases reported in literatures, the high amylase level did not revert to normal after the withdrawal of medications. The patient was discharged from hospital with a high level of amylase, and was placed under follow-up observations.

Conclusion

Acute pancreatitis is considered as one of the idiosyncratic adverse reactions to antiepileptic drugs. Previous reports were mainly on the pediatric patients with increased propensity to idiosyncratic drug effects, or the adult chronic renal failure patients with sodium valproate-induced pancreatitis due to the retention of intermediate metabolites in their bodies. In this study, even though our patient exhibited no high risk of developing pancreatitis, he was treated for drug-induced acute pancreatitis in three hospitals. As rare as drug-induced acute pancreatitis can be, it should not be overlooked, Moreover, the mechanism of how sodium valproate induces acute pancreatitis remains unknown. Therefore, physicians need to consider the medical history of patients before prescribing this medication.
Strategic entrepreneurship, competitive advantage, and SMEs’ performance in the welding industry in Tanzania
Authors: Kiyabo Kibeshi , Isaga Nsubili
Published: November 2019

This study aimed at obtaining empirical evidence regarding the influence of strategic entrepreneurship on SMEs’ performance under the mediation of competitive advantage in the welding industry in Tanzania. Guided by the resource-based theory, this study adopted learning orientation, strategic resource management, and entrepreneurial orientation as strategic entrepreneurship components. Survey method with cross-sectional design was used to collect data from 300 owners-managers of welding industry SMEs located in Dar es Salaam, Morogoro, and Mbeya urban centers. Structural equation modelling technique was used to develop measurement and structural models. Findings suggest that learning orientation influences entrepreneurial orientation which influences strategic resource management to create competitive advantage that promotes SMEs’ performance. Findings of this study imply that the resource-based theory holds a better chance to describe the influence of strategic entrepreneurship components on SMEs’ performance under the mediation of competitive advantage than the individual resource-based view and knowledge-based view. It has been empirically demonstrated that knowledge is a unique resource that enables the acquisition of other resources and strategies. SMEs are urged to embrace learning orientation to create competitive advantage that leads to superior performance. The study has empirically verified that learning orientation, strategic resource management, and entrepreneurial orientation constructs adopted from entrepreneurship and strategic management literature are components of strategic entrepreneurship. Inclusion of strategic entrepreneurship components, competitive advantage, and SMEs’ performance with their composite measures in a single model distinguishes this study from past studies.
Long non-coding RNA MALAT1 enhances the apoptosis of cardiomyocytes through autophagy inhibition by regulating TSC2-mTOR signaling
Authors: Hu Hao , Wu Jiawei , Yu Xiaofan , Zhou Junling , Yu Hua , Ma Likun
Published: November 2019

Background

Our previous study showed that knockdown of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) attenuated myocardial apoptosis in mouse acute myocardial infarction (AMI). This study aims to explore whether MALAT1 enhanced cardiomyocyte apoptosis via autophagy regulation and the underlying mechanisms of MALAT1 regulating autophagy.

Methods

Cardiomyocytes were isolated from neonatal mice and then stimulated with hypoxia/reoxygenation (H/R) injury to mimic AMI. The autophagy level was assessed using GFP-LC3 immunofluorescence and western blot analysis of autophagy-related proteins. RNA pull-down and RNA immunoprecipitation (RIP) was performed to analyze the binding of MALAT1 and EZH2. Chromatin immunoprecipitation (ChIP) assay was performed to analyze the binding of TSC2 promoter and EZH2. The cell apoptosis was evaluated using TUNEL staining and western blot analysis of apoptosis-related proteins.

Results

H/R injury increased MALAT1 expression in cardiomyocytes. Furthermore, MALAT1 overexpression inhibited, whereas MALAT1 knockdown enhanced the autophagy of cardiomyocytes. Moreover, MALAT1 overexpression recruited EZH2 to TSC2 promoter regions to elevate H3K27me3 and epigenetically inhibited TSC2 transcription. Importantly, TSC2 overexpression suppressed mTOR signaling and then activated the autophagy. Further results showed that MALAT1 inhibited proliferation and enhanced apoptosis of cardiomyocytes through inhibiting TSC2 and autophagy.

Conclusion

These findings demonstrate that the increased MALAT1 expression induced by H/R injury enhances cardiomyocyte apoptosis through autophagy inhibition by regulating TSC2-mTOR signaling.
Pure pancreatic hepatoid carcinoma: a surgical case report and literature review
Authors: Tomino Takahiro , Ninomiya Mizuki , Matono Rumi , Narutomi Fumiya , Oshiro Yumi , Watanabe Kenji , Taniguchi Daisuke , Nishimura Sho , Zaitsu Yoko , Kajiwara Yuichiro , Yokota Tomoyuki , Minami Kazuhito , Nishizaki Takashi
Published: November 2019

Background

Hepatoid carcinoma (HC) is an extra-hepatic neoplasm that shares the morphological and immunohistochemical features of hepatocellular carcinoma. Pancreatic HC exists as either pure or combined type. Pure pancreatic HC is extremely rare, with only a few cases reported in the literature to date. Because of the rarity of pure pancreatic HC, its clinical features including incidence, behavior, and prognosis remain unclear. We herein report the case of a 56-year-old man who developed pure pancreatic HC treated with surgical resection. We also include a review of the existing literature.

Case presentation

A 56-year-old male patient was admitted to our hospital after a pancreatic cyst was identified by abdominal ultrasonography on a comprehensive medical examination. Endoscopic ultrasound revealed a cystic mass measuring 13 mm in size in the pancreatic head and a low-density mass measuring 16 mm in size in the pancreatic tail, which was partially enhanced on contrast-enhanced ultrasound. Contrast-enhanced computed tomography (CT) revealed a branch duct type intraductal papillary mucinous neoplasm in the pancreatic head and an early enhanced nodule measuring approximately 10 mm in size in the pancreatic tail. Endoscopic ultrasound-guided fine-needle aspiration of the hypervascular tumor was performed. The hypervascular tumor was suspected to be a solid pseudopapillary neoplasm. Laparoscopic spleen-preserving distal pancreatectomy was performed. Histology was identical to hepatocellular carcinoma of the liver. Immunohistochemically, the tumor cells were positive for hepatocyte paraffin 1, and a canalicular pattern was confirmed on the polyclonal carcinoembryonic antigen staining. The patient was diagnosed with a moderately differentiated pancreatic HC. The patient was followed up without adjuvant chemotherapy, and there was no evidence of recurrence at 6 months post-operatively.

Conclusions

We present a case of moderately differentiated pure pancreatic HC. For the accurate preoperative diagnosis of pure pancreatic HC, biopsy is preferred to cytology or preoperative imaging studies such as CT. The prognosis of pure pancreatic HC depends on its differentiation.
Histopathological study of invasive and non-invasive Entamoeba spp. in experimental rats
Authors: Al-Hilfi Athraa Abd-ulameer , Al-Malak Maha Khalil , Al-Tomah Muslim Abd-ulrahman
Published: November 2019

Background

The genus Entamoeba has many species that are invasive or non-invasive (E. histolytica, E. dispar, and E. moshkovskii).The invasive E. histolytica is the main pathogenic amoeba in human. Amoebiasis involves several stages starting with the adherence of the parasite to the intestinal epithelium, followed by degradation, tissue invasion, and distribution to other organs.

Results

The current study investigates the pathological changes of Entamoeba spp. infection in both rectum and cecum of experimental rats. The results showed the histological changes at the 7th, 14th, and 28th day post-infection for the three species. E. histolytica and E. moshkovskii infection showed less pathological changes compared to E. histolytica. These changes include the attachment of the trophozoites to the mucosal layer, significant surface epithelial changes such as dissociation and degeneration in the mucosal layer, and ulceration of the apical surface. Inflammatory cells infiltrate the varied regions, extending into the deep mucosa causing mild architectural alterations. These are features of amoebiasis.

Conclusion

The pathological changes reported in E. dispar and E. moshkovskii were less severe than E. histolytica.
The validity of HSG in infertility work up
Authors: Ahmed Shimaa Abdalla , Abo-taleb Hisham
Published: November 2019

Background

Our purpose was to evaluate the diagnostic accuracy of hysterosalpingography (HSG) in the diagnosis of the uterine cavity and tuboperitoneal abnormalities in infertile women. Reproducibility and consistency were also assessed. Two hundred infertile females underwent HSG, hysteroscopy, and/or laparoscopy as part of infertility workup. HSG examinations were retrospectively reviewed by three radiologists; we compared interobserver variability, and differences between the two results of reading the same examination after 3 months were compared to calculate intraobserver variability.

HSG sensitivity, specificity, PPV, NPV, and accuracy were calculated.

Results

The overall accuracy of HSG in diagnosing tubal, uterine cavity, and peritoneal abnormalities was 95.5%, 95%, and 89%, respectively (P value < 0.04).

HSG is reproducible in diagnosing normal versus abnormal examinations. Reproducibility in diagnosing uterine cavity, tubal, and peritoneal abnormalities was (ICC = 0.90), (ICC = 0.70), and (ICC = 0.31), respectively. Best agreement was seen in diagnosing luminal filling defect (sub mucous fibroid/polyp) (ICC = 0.90) (95% CI 0.86–0.98), whereas poorest agreement was found in diagnosing uterine adhesions (ICC = 0.13) (95% CI 0.10–0.13) and pelvic adhesions (ICC = 0.12) (95% CI 0.10–0.13) (P value < 0.03).

HSG consistency ranged from moderate to good (K = 0.49–0.79). It was highest in diagnosing normal versus abnormal examination (P value < 0.01); poorest in diagnosing pelvic adhesions.

Conclusion

HSG has high validity in negative results; it can minimize the use of invasive procedures. Laparoscopy is recommended in patients who had a pelvic disease or showing tubal obstruction on HSG.
Community College Instructors’ Perceptions of Constraints and Affordances Related to Teaching Quantitative Biology Skills and Concepts
Authors: Corwin Lisa A. , Kiser Stacey , LoRe Sondra M. , Miller Jillian M. , Aikens Melissa L.
Published: November 2019

Quantitative skills are an important competency for undergraduate biology students and should be incorporated early and frequently in an undergraduate’s career. Community colleges (CCs) are responsible for teaching introductory biology to a large proportion of biology and prehealth students, and quantitative skills are critical for their careers. However, we know little about the challenges and affordances that CC instructors encounter when incorporating quantitative skills into their courses. To explore this, we interviewed CC biology instructors ( n = 20) about incorporating quantitative biology (QB) instruction into their classes. We used a purposeful sampling approach to recruit instructors who were likely to have tried evidence-based pedagogies and were likely aware of the importance of QB instruction. We used open coding to identify themes related to the affordances to and constraints on teaching QB. Overall, our study participants met with challenges typical of incorporating new material or techniques into any college-level class, including perceptions of student deficits, tension between time to teach quantitative skills and cover biology content, and gaps in teacher professional knowledge (e.g., content and pedagogical content knowledge). We analyze these challenges and offer potential solutions and recommendations for professional development to support QB instruction at CCs.
Genomic analysis of lncRNA and mRNA profiles in circulating exosomes of patients with rheumatic heart disease
Authors: Luo Yanli , Huang Lingjin , Luo Wanjun , Ye Shu , Hu Qinghua
Published: November 2019

Rheumatic heart disease (RHD) remains one of the most common cardiovascular conditions in developing countries. Accumulating evidence suggests that circulating exosomes and their cargoes, including mRNA and long noncoding RNA (lncRNA), play essential roles in many cardiovascular diseases. However, their specific roles in RHD remain unexplored. In the present study, we identified 231 lncRNAs and 179 mRNAs differentially expressed in the circulating exosomes harvested from RHD patients compared to healthy controls. We performed gene ontology (GO) and KEGG pathway analysis, and identified 5 pairs of lncRNAs and their flanking coding genes simultaneously dysregulated in the circulating exosomes. Collectively, we provide the first transcriptome analysis identifying differentially expressed lncRNAs and mRNAs in circulating exosomes of RHD patients, which may bring valuable insights for the discovery of potential biomarkers and therapeutic targets for RHD.
Optimization of high endoglucanase yields production from polypore fungus, Microporus xanthopus strain KA038 under solid-state fermentation using green tea waste
Authors: Nguyen Kim Anh , Kumla Jaturong , Suwannarach Nakarin , Penkhrue Watsana , Lumyong Saisamorn
Published: November 2019

Polypores are diverse macrofungi that have been extensively studied for their lignocellulolytic enzyme production capabilities. Currently, these enzymes are being used for many industrial purposes. However, the high cost associated with their production is the main barrier to their broader application. This work aimed to study the optimal medium and conditions for endoglucanase production using solid state fermentation. Seven polypore strains were used for endoglucanase activity screening. The fermentation experiments were carried out in 250 ml Erlenmeyer flasks with green tea waste as a substrate. Notably, Microporus xanthopus strain KA038 showed the best level of activity (38.62 IU/gds). Various parameters such as moisture content, nitrogen source, initial pH value, inoculum size and incubation time were considered to determine the optimal conditions for endoglucanase production. The optimal medium consisted of green tea leaves as a carbon source, beef extract as an organic nitrogen source, NH4H2PO4 as an inorganic nitrogen source, pH 7.0 and an incubation temperature at 30°C for 4 days resulted in a high enzyme yield with M. xanthopus strain KA038 (81.8 IU/gds).

This article has an associated First Person interview with the first author of the paper.
Real-Time Monitoring of Low Pressure Oxygen Molecules over Wide Temperature Range: Feasibility of Ultrathin Hybrid Films of Iridium(III) Complexes and Clay Nanosheets
Authors: Sato Hisako , Takimoto Kazuyoshi , Kato Masaru , Nagaoka Shin-ichi , Tamura Kenji , Yamagishi Akihiko
Published: November 2019

An ultrathin film was prepared by hybridizing a cationic Ir(III) complex with exfoliated nanosheets of clay minerals such as natural montmorillonite (denoted by MON) or synthetic saponite (denoted by SAP). The utilized Ir(III) complex with two long alkyl chains was [Ir(dfppy)2(dc9bpy)]+ (fppyH = 2-(2′,4′-difluorophenyl)pyridine; dc9bpy = 4,4′-dinonyl-2,2′-bipyridine) (denoted by DFPPY). Hybridization was performed at an air-water interface between a floating monolayer of the Ir(III) complex and the nanosheets exfoliated in an aqueous subphase. The hybrid floating film thus formed was transferred onto a hydrophilic quartz plate by a vertical dipping method. The emission from the deposited films exhibited rapid reversible change of intensity in response to the introduction or evacuation of oxygen gas in the pressure range of 0.1–101.3 kPa and the temperature range from 253 K to 313 K. The lifetime of the emission decay was measured as a function of oxygen pressure, confirming the occurrence of dynamic quenching of excited Ir(III) complexes by oxygen molecules.
Concentrated Battery Electrolytes: Developing New Functions by Manipulating the Coordination States
Authors: Yamada Yuki
Published: November 2019

The basic formula of Li-ion battery electrolytes (i.e., LiPF6 and ethylene carbonate) has remained unchanged ever since commercialization in the early 1990s. However, toward advanced batteries with higher energy density and higher safety, a new electrolyte design that leads to better functions is required. Recently, various new functions have been discovered for highly concentrated electrolytes (over 3 mol dm−3 (M) vs. standard 1 M), which arises from their unique coordination states of ions and solvent molecules. Based on this achievement, the coordination states are increasingly recognized as key to further functionalizing battery electrolytes. This account introduces an electrolyte design based on the coordination states and provides future visions on rechargeable batteries that will be realized thereby.
Novel imaging biomarkers: epicardial adipose tissue evaluation
Authors: Monti Caterina B. , Codari Marina , De Cecco Carlo Nicola , Secchi Francesco , Sardanelli Francesco , Stillman Arthur E.
Published: November 2019

Epicardial adipose tissue (EAT) is a metabolically activated beige adipose tissue, non-homogeneously surrounding the myocardium. Physiologically, EAT regulates toxic fatty acids, protects the coronary arteries against mechanical strain, regulates proinflammatory cytokines, stimulates the production of nitric oxide, reduces oxidative stress, and works as a thermogenic source against hypothermia. Conversely, EAT has pathologic paracrine interactions with the surrounded vessels, and might favour the onset of atrial fibrillation. In addition, initial atherosclerotic lesions can promote inflammation and trigger the EAT production of cytokines increasing vascular inflammation, which, in turn, may help the development of collateral vessels but also of self-stimulating, dysregulated inflammatory process, increasing coronary artery disease severity. Variations in EAT were also linked to metabolic syndrome. Echocardiography first estimated EAT measuring its thickness on the free wall of the right ventricle but does not allow accurate volumetric EAT estimates. Cardiac CT (CCT) and cardiac MR (CMR) allow for three-dimensional EAT estimates, the former showing higher spatial resolution and reproducibility but being limited by radiation exposure and long segmentation times, the latter being radiation-free but limited by lower spatial resolution and reproducibility, higher cost, and difficulties for obese patients. EAT radiodensity at CCT could to be related to underlying metabolic processes. The correlation between EAT and response to certain pharmacological therapies has also been investigated, showing promising results. In the future, semi-automatic or fully automatic techniques, machine/deep-learning methods, if validated, will facilitate research for various EAT measures and may find a place in CCT/CMR reporting.
Self-Diagnosis of Surgical Site Infections: Lessons from a Tertiary Care Centre in Karachi, Pakistan
Authors: Sajun Sana Z , Albutt Katherine , Moosajee Umme Salama , Drevin Gustaf , Mukhopadhyay Swagoto , Samad Lubna
Published: November 2019

Background and Objective: Surgical site infections (SSIs) usually manifest post-discharge, rendering accurate diagnosis and treatment challenging, thereby catalyzing the development of alternate strategies like self-monitored SSI surveillance. This study aims to evaluate the diagnostic accuracy of patients and Infection Control Monitors (ICMs) to develop a replicable method of SSI-detection.

Methods: A two-year prospective diagnostic accuracy study was conducted in Karachi, Pakistan between 2015 and 2017. Patients were educated about SSIs and provided with questionnaires to elicit symptoms of SSI during post-discharge self-screening. Results of patient’s self-screening and ICM evaluation at follow-ups were compared to surgeon evaluation.

Results: A total of 348 patients completed the study, among whom 18 (5.5%) developed a SSI. Patient self-screening had a sensitivity of 39%, specificity of 95%, positive predictive value (PPV) of 28%, and negative predictive value (NPV) of 97%. ICM evaluation had a sensitivity of 82%, specificity of 99%, PPV of 82%, and NPV of 99%.

Conclusion: Patients cannot self-diagnose a SSI reliably. However, diagnostic accuracy of ICMs is significantly higher and they may serve as a proxy for surgeons, thereby reducing the burden on specialized surgical workforce in LMICs. Regardless, supplementing post-discharge follow-up with patient self-screening could increase SSI-detection and reduce burden on health systems.

doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1716

How to cite this:Sajun SZ, Albutt K, Moosajee US, Drevin G, Mukhopadhyay S, Samad L. Self-Diagnosis of Surgical Site Infections: Lessons from a tertiary care centre in Karachi, Pakistan. Pak J Med Sci. Special Supplement ICON 2020. 2020;36(1):S55-S60.  doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1716

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.
The role of the poultry industry on kidney and genitourinary health in Pakistan
Authors: Imtiaz Salman , Alam Ashar , Salman Beena
Published: November 2019

Pakistan is experiencing a “double burden’’ of disease. Under-development is associated with illnesses like infections and nutritional deficiency, and is accompanied with diseases linked with development, such as diabetes, hypertension, cancer and chronic kidney disease. In Pakistan, renal and genitourinary diseases are an important, unaddressed health issues. Chronic kidney disease of unknown etiology (CKDu) is a recognized form of renal failure in Pakistan. A possible cause of CKDu is toxins such as arsenic, cadmium, lead and other heavy metals associated with renal and genitourinary diseases. The poultry industry is an important source of both heavy metal toxins and also mycotoxins spread in the process of farming. Of the numerous mycotoxins, zearalenone and ochratoxin are well-known for their hazardous effects on genitourinary and renal parenchyma respectively. We reviewed the literature using PubMed and Google Scholar databases for levels of these toxins in various constituents of chicken farming like chicken feed, meat, litter and human drinking water contamination in various parts of the country. We found that these toxins are in higher levels than recommended.

doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1718

How to cite this:Imtiaz S, Alam A, Salman B. The role of the poultry industry on kidney and genitourinary health in Pakistan. Pak J Med Sci. Special Supplement ICON 2020. 2020;36(1):S67-S74. doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1718

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.
Retinoblastoma Presentation and Survival: A four-year analysis from a tertiary care hospital
Authors: Zia Nida , Ahmer Hamid Ahmer , Iftikhar Sundus , Qadri Muhammad Hamza , Jangda Anzal , Khan Muhammad Rahil
Published: November 2019

Objective: To study the clinical presentation, treatment, and outcome of Retinoblastoma (Rb) in a tertiary care hospital of Pakistan.

Methods: A retrospective study was conducted in the Department of Pediatric Hematology Oncology, The Indus Hospital (TIH), Karachi from 1st June 2013 to 30th June 2017. Data including patients’ demography, clinical symptoms and duration, laterality, extent of the tumor, type of treatment, relapse, and final outcome were extracted and evaluated with respect to progression and survival.

Results: A total of 93 patients were included; 34.4% were boys. The median age at presentation was 30 months. Leukocoria was the commonest symptom (61.3%), followed by proptosis (37.6%). Unilateral disease was seen in 59.1%, extraocular tumors in 43.5% and metastasis in 28.1%. Enucleation was performed on 46.2%, chemotherapy given to 80.6% and external beam radiation therapy to 29.3% patients.

Conclusion: Delayed presentation, recurrent disease, extraocular disease and metastasis on presentation were factors affecting outcome in our cohort. Awareness about the early warning signs and symptoms in both public and health professionals for early recognition and timely management are mandatory to decrease morbidity and mortality.

doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1720

How to cite this:Zia N, Hamid A, Iftikhar S, Qadri MH, Jangda A, Khan MR. Retinoblastoma Presentation and Survival: A four-year analysis from a tertiary care hospital. Pak J Med Sci. Special Supplement ICON 2020. 2020;36(1):S61-S66. doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1720

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.
Abdominal actinomycosis in an elderly diabetic
Authors: Memon Riyasat Ahmed , Shafquat Yusra , Yaqoob Nausheen
Published: November 2019

Actinomycosis is a rare infectious disease that presents as three entities, cervico-facial, abdominal and genital, with cervico-facial being the commonest. Due to its subacute presentation and indolent course, abdominal actinomycosis is difficult to diagnose and is often confused with malignancy. We present a case of an elderly diabetic with no known other risk factors of the disease with complaints of right sided abdominal swelling and presence of abdominal mass on imaging, diagnosed post operatively as a case of abdominal actinomycosis, on histopathology. Abdominal actinomycosis should be considered in differentials in cases with abdominal masses. Diabetes Mellitus is not an established risk factor for development of abdominal actinomycosis. Studies are required to link its association with the disease.

doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1724

How to cite this:Memon RA, Shafquat Y, Yaqoob N. Abdominal actinomycosis in an elderly diabetic. Pak J Med Sci. Special Supplement ICON 2020. 2020;36(1):S98-S100. doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1724

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.
Advances in clinical staging, early intervention, and the prevention of psychosis
Authors: Gupta Tina , Mittal Vijay A.
Published: November 2019

The development of effective intervention and prevention strategies among individuals with psychosis risk syndromes may help to reduce symptomatology and conversion to a psychotic disorder. Although strides have been made in this area, more work is needed, particularly given the setbacks that remain (such as heterogeneity among this group). There has been a shift with the introduction of clinical staging models toward expanding current intervention and prevention efforts to a more developmental and transdiagnostic approach. With this, this article seeks to review treatments both recently and currently discussed in the staging literature, introduce advances in psychosis risk syndrome treatments that may be beneficial to consider in clinical staging heuristics, and pinpoint other promising options.
Recent advances in perinatal neuroprotection
Authors: Singhi Samata , Johnston Michael
Published: November 2019

Perinatal brain injury is a major cause of neurological disability in both premature and term infants. In this review, we summarize the evidence behind some established neuroprotective practices such as administration of antenatal steroids, intrapartum magnesium for preterm delivery, and therapeutic hypothermia. In addition, we examine emerging practices such as delayed cord clamping, postnatal magnesium administration, recombinant erythropoietin, and non-steroidal anti-inflammatory agents and finally inform the reader about novel interventions, some of which are currently in trials, such as xenon, melatonin, topiramate, allopurinol, creatine, and autologous cord cell therapy.
The Importance of Children’s Positive Thinking Development in Order to Improve Their Health
Authors: Kashicyna Yu. , Guruleva T.
Published: November 2019

The article discusses some aspects of positive thinking in children in order to improve their health. Particular attention is paid to the development of positive thinking. The process of mental activity is described to the features of the formation of positive thinking. The article is addressed to teachers and teachers, students of pedagogical universities, methodologists
APRENDIZAJE MATEMÁTICO Y ESTRATEGIAS DE IDENTIDAD. UN CASO DE EDUCACIÓN DE PERSONAS ADULTAS EN BRASIL
Authors: Pompeu Carla Cristina , Gómez-Chacón Inés M.
Published: November 2019

En este artículo se analiza la educación de personas adultas en Brasil. La investigación busca identificar cómo las identidades sociales configuran las identidades matemáticas de los sujetos y cómo la construcción y negociación de identidad social afecta a la interacción en el proceso de enseñanza y aprendizaje en el aula. Basados en una metodología cualitativa se han descrito escenarios donde la identidad social se actualiza en el aprendizaje de la matemática y cómo ésta configura elementos facilitadores u obstaculizadores para el aprendizaje. Los resultados ponen de manifiesto las relaciones con los saberes matemáticos, y cómo sujetos de un mismo grupo social y/o cultural se relacionan con las matemáticas de diferentes modos según información, experiencia y posicionamiento de identidad.