bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cushing Syndrome in a Pediatric Patient With a KCNJ5 Variant and Successful Treatment With Low-dose Ketoconazole
Authors: Tatsi Christina , Maria Andrea G , Malloy Cole , Lin Lin , London Edra , Settas Nick , Flippo Chelsi , Keil Meg , Hannah-Shmouni Fady , Hoffman Dax A , Stratakis Constantine A 
Published: February 2021

Abstract

Context
Pathogenic variants in KCNJ5, encoding the GIRK4 (Kir3.4) potassium channel, have been implicated in the pathogenesis of familial hyperaldosteronism type-III (FH-III) and sporadic primary aldosteronism (PA). In addition to aldosterone, glucocorticoids are often found elevated in PA in association with KCNJ5 pathogenic variants, albeit at subclinical levels. However, to date no GIRK4 defects have been linked to Cushing syndrome (CS).

Patient
We present the case of a 10-year-old child who presented with CS at an early age due to bilateral adrenocortical hyperplasia (BAH). The patient was placed on low-dose ketoconazole (KZL), which controlled hypercortisolemia and CS-related signs. Discontinuation of KZL for even 6 weeks led to recurrent CS.

Results
Screening for known genes causing cortisol-producing BAHs (PRKAR1A, PRKACA, PRKACB, PDE11A, PDE8B, ARMC5) failed to identify any gene defects. Whole-exome sequencing showed a novel KCNJ5 pathogenic variant (c.506T&gt;C, p.L169S) inherited from her father. In vitro studies showed that the p.L169S variant affects conductance of the Kir3.4 channel without affecting its expression or membrane localization. Although there were no effects on steroidogenesis in vitro, there were modest changes in protein kinase A activity. In silico analysis of the mutant channel proposed mechanisms for the altered conductance.

Conclusion
We present a pediatric patient with CS due to BAH and a germline defect in KCNJ5. Molecular investigations of this KCNJ5 variant failed to show a definite cause of her CS. However, this KCNJ5 variant differed in its function from KCNJ5 defects leading to PA. We speculate that GIRK4 (Kir3.4) may play a role in early human adrenocortical development and zonation and participate in the pathogenesis of pediatric BAH.
Development of a Predictive Enrichment Marker for the Oral GH Secretagogue LUM-201 in Pediatric Growth Hormone Deficiency
Authors: Bright George M , Do Minh-Ha T , McKew John C , Blum Werner F , Thorner Michael O 
Published: February 2021

Abstract

Context
We hypothesize, based on the degree of residual hypothalamic-pituitary function, that some, but not all, children with growth hormone deficiency (GHD) may have beneficial growth responses to the orally administered growth hormone (GH) secretagogue LUM-201.

Objective
To determine if pretreatment testing can identify predictive enrichment markers (PEM) for subjects with adequate residual function who are responsive to LUM-201.

Methods
We performed an analysis of a completed, randomized, placebo-controlled trial of LUM-201, a GH secretagogue receptor agonist, in which all randomized subjects had pretreatment testing.
This international multicenter study conducted in pediatric endocrinology clinics included 68 naïve-to-treatment, prepubertal children with established diagnoses of GHD. Outcome measures included the sensitivity, specificity, and predictive accuracy of potential markers to predict 6-month growth responses to oral LUM-201 and daily rhGH.

Results
Two PEM were identified for use in defining PEM-positive status: (1) baseline insulin-like growth factor I (IGF-I) concentration &gt;30 ng/mL and (2) peak GH response of ≥5 ng/mL upon administration of single-dose LUM-201. PEM-positive status enriches a population for better growth responses to LUM-201. PEM-negative status enriches a population for better growth responses to rhGH.

Conclusion
Combined, the peak GH response to single-dose LUM-201 and the baseline IGF-I concentration are effective PEMs for 6-month growth responses to LUM-201 and rhGH in prepubertal children with GHD.
Association amid the comorbidity of Diabetes Mellitus in patients of Active Tuberculosis in Pakistan: A matched case control study
Authors: Khalid Nadia , Ahmad Farah , Qureshi Farhan Muhammad 
Published: February 2021

Objectives: This study aims to test the association between diabetes and tuberculosis.
Methods: It is a matched case control study conducted in tertiary care hospitals in 2019-2020. Cases and controls were 144 each, selected on the basis of an odds ratio of 2 at 95% confidence interval with a significance level of 5%. Cases of pulmonary tuberculosis were selected through consecutive sampling technique, either visiting OPD or admitted in hospital. Controls were taken from the general population and frequency matching was done based on age, gender and socioeconomic status. Data was collected through structured questionnaire after taking written consent. Data was analyzed on SPSS version 23. Binary Logistic regression model was applied for finding association between the risk factors and the disease. P value <0.05 was considered statistically significant.
Results: Out of all cases and controls, 45% and 20% were diabetics respectively. The association between the risk factors and tuberculosis was estimated by univariate analysis, positive association was found between diabetes and tuberculosis (OR= 3.32), a high frequency of diabetes in cases as compared to controls were observed with a highly significant p- value (<0.001).
Conclusions: This study provides evidence for a strong positive association between tuberculosis and diabetes.
doi: https://doi.org/10.12669/pjms.37.3.3274
How to cite this:Khalid N, Ahmad F, Qureshi FM. Association amid the comorbidity of Diabetes Mellitus in patients of Active Tuberculosis in Pakistan: A matched case control study. Pak J Med Sci. 2021;37(3):816-820. doi: https://doi.org/10.12669/pjms.37.3.3274
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.
Rare Variant of Adult Rhabdomyosarcoma Presenting as a Palatal Swelling
Authors: Iqbal Hafiz Aamer , Anjum Rabia , Naseem Nadia 
Published: February 2021

A 26-year-old male was referred to the Department of Oral and Maxillofacial Surgery of a tertiary care hospital in Lahore with chief complaint of painless swelling on the right palate of 40 days duration. Clinical differential diagnosis included squamous cell carcinoma, Ewing sarcoma, fibrosarcoma, neuroblastoma and rhabdomyosarcoma. Computed tomography scan revealed hypodense mass with necrotic changes. Histological examination of the excised tumor revealed malignant neoplasm arranged in fascicles and bundles comprising of spindle cells with pleomorphic, hyperchromatic nuclei and increased atypical mitosis. Immunohistochemical analysis showed negative staining with Cytokeratin, S100, CD34, Stat6, h-Caldesmon and EMA while the tumour cells were positive for desmin, myogenin, smooth muscle actin, CD-99 and MyoD1 thus confirming the diagnosis of spindle cell rhabdomyosarcoma.
doi: https://doi.org/10.12669/pjms.37.3.3305
How to cite this:Iqbal HA, Anjum R, Naseem N. Rare Variant of Adult Rhabdomyosarcoma Presenting as a Palatal Swelling. Pak J Med Sci. 2021;37(3):922-925. doi: https://doi.org/10.12669/pjms.37.3.3305
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.
Patterns and Outcomes of dog bite injuries presenting to emergency department in a tertiary care hospital at Karachi
Authors: Ali Muhammad Ikram , Jamali Seemin , Ashraf Tehreem , Ahmed Nasibullah 
Published: February 2021

Objectives: To assess patterns & outcomes of dog bite injuries coming to a public sector tertiary care hospital in Karachi, Pakistan.
Methods: This was a one-year descriptive cross sectional study from 1st June 2018- 31st May 2019 using consecutive sampling technique. Data of 7512 patients was collected from animal-bite clinic of a tertiary care hospital. Inclusion criteria was animal bite cases that were reported during the dates 1st June 2018 to 31st May 2019, Incomplete records were excluded. Data comprising of time of bite, the location of the victim at the time of bite within the city, animal responsible for the bite, gender and age of victim, date of presentation, site and category of bite (as per WHO criteria) was recorded by the primary investigator. The study was conducted at Jinnah Post-Graduate Medical Centre.
Results: Among 7512 participants 85.8% were males, 32.2% victims reported time of bite between morning and noon, 78.8% of bites involved lower limbs. 51.6% of the bites belonged to category 2. Stray dog bites were observed in 90.3% of cases. Outcome showed 54.9% completed their vaccination, while 44.3% did not show for complete follow up, 3.99% bites were grievous & 0.03% reported with developed rabies.
Conclusion: Research reveals Males belonging to adult age group were most vulnerable, most bites were inflicted in early hours, most common animal inflicting the bites were stray dogs. Many victims did not complete their vaccination from the same centre. Peak of the summer was associated with a decline in number of incidents.
doi: https://doi.org/10.12669/pjms.37.3.3464
How to cite this:Ali MI, Jamali S, Ashraf T, Ahmed N. Patterns and Outcomes of dog bite injuries presenting to emergency department in a tertiary care hospital at Karachi. Pak J Med Sci. 2021;37(3):794-799. doi: https://doi.org/10.12669/pjms.37.3.3464
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.
Spectrum of associated congenital heart defects in patients with “Non-Cardiac Congenital defects at a tertiary care children hospital in Pakistan”
Authors: Arshad Muhammad Sohail , Aslam Muhammad , Ahmad Shahnab , Kashif Muhammad 
Published: February 2021

Objectives: To assess the frequency and pattern of associated congenital heart disease (CHD) among patients with “non-cardiac congenital defects”.
Methods: An observational study was done at Paediatric Cardiology Department, The Children’s Hospital and The Institute of Child Health, Multan, Pakistan, from December 2018 to November 2019. Children from birth to 15 years having non-cardiac congenital defects, referred for cardiac evaluation from surgical unit during the study period were enrolled. Echocardiography was done to confirm diagnosis of CHD by consultant pediatric cardiologist.
Results: Out of a total of 323 cases, 176 (54.5%) were male. Out of 323 patients, 160 (49.5%) belonged to age one month to one year. Vascular malformations were the most frequent primary diagnosis among our cases, seen in 69 (21.4%) children followed by cleft lip and palate 55 (17.2%), cleft palate only 52 (16.1%), Cleft lip only 40 (12.4%) and ARM high variety 33 (10.2%). CHD was found among 42 (13.0%) children while patent ductus arteriosus (PDA) and VSD were the commonest finding seen in 14 (33.3%) and 6 (14.3%) children respectively.
Conclusion: Frequency of associated CHD among patients with non-cardiac congenital defects was high (13.0%). Children with cleft lip and/or palate should be given more attention because of the high incidence of CHD in this group. Echocardiography must be advised for the timely identification of any possible type of CHD.
doi: https://doi.org/10.12669/pjms.37.3.3604
How to cite this:Arshad MS, Aslam M, Ahmad S, Kashif M. Spectrum of associated congenital heart defects in patients with “Non-Cardiac Congenital defects at a tertiary care children hospital in Pakistan”. Pak J Med Sci. 2021;37(3):695-699. doi: https://doi.org/10.12669/pjms.37.3.3604
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 effectiveness of community neurorehabilitation for persons with an acquired brain injury: protocol for a systematic review
Authors: Mitchell Eileen , Philips Nicola , Ahern Elayne , McGettrick Grainne , Mockler David , Fitzpatrick Kyle , Trepel Dominic 
Published: February 2021

Background: Acquired brain injury (ABI) refers to any type of brain damage after birth. ABI from either traumatic or non-traumatic origin is a leading cause of death and long-term disability globally. The impact of an ABI can be cognitive and/ or physical, greatly affecting their ability to function independently. With a lack of specialist inpatient rehabilitation facilities and services many of these survivors reside within the community either alone, with family or in residential facilities. Up-to-date evidence is required to indicate which forms of community rehabilitation are most effective in improving cognitive and physical outcomes for survivors. This systematic review aims to explore the clinical effectiveness of community neuro-rehabilitation services for persons living with an ABI. Methods: A systematic review of relevant electronic databases will be undertaken to identify eligible published randomised controlled trials. The PRISMA statement will be used to guide the systematic review. From running the initial search, we aim to submit the paper for publishing within 6 months. This process will be completed using Covidence software. Two reviewers will independently screen the search results and select studies using pre-defined selection criteria, extract data from and assess risk of bias for selected studies. Discussion: This systematic review will aim to explore the clinical effectiveness of community neuro-rehabilitation services for persons with an ABI. It plans to review and synthesize the current best available evidence base. A goal of this study is to positively inform ongoing service development within a quality framework. Systematic review registration: PROSPERO CRD42020148604 (26/02/2020)
Mortgage Brokers and the Effectiveness of Regulatory Oversights
Authors: Agarwal Sumit , Ang Swee Hoon , Deng Yongheng , Wang Yonglin 
Published: February 2021

This paper studies the responses among different types of mortgage brokers to occupational licensing regulations. By explicitly accounting for heterogeneities between sole and corporate brokers, we find evidence that sole brokers respond to financial regulatory oversight by applying a more stringent screening process in conducting brokerage activities, hence achieving better loan performances. Specifically, loans originated through sole brokers exhibit higher quality on an array of credit-relevant characteristics, including those reported and unreported to future investors. By contrast, we find no such regulatory effect on corporate brokers who tend to rely extensively on reported characteristics that are critical to the subsequent loan securitization at the expense of unreported information despite the latter indicating potential risks. Hence, the agency problem among sole brokers can be mitigated by the consolidated financial requirement for occupational licensing. However, such provision is ineffective in governing corporate brokers. Additionally, welfare gains associated with the occupational licensing regulation are achieved at the expense of prospective borrowers paying a higher loan price and having reduced credit access. Stricter licensing regulations may induce welfare loss related to credit rationing as reasonable loan applications are not funded, including those with potentially lower default risk. This paper was accepted by Kay Giesecke, finance.
pensamento, experiência e o tempo do ócio na educação infantil
Authors: Venturini Gabriela , Schuler Betina 
Published: February 2021

This paper aims to examine the way that the concepts of thought and interest have been described in the three main documents that currently guide Brazilian Child Education – National Education Guidelines and Bases/1996, National Curriculum Guidelines for Child Education/2010, and National Curriculum Basis/2018 for Child Education – and their implications for relations between childhood and thinking. In order to do that, we have relied on studies in the philosophy of difference, considering authors such as Kohan, Larrosa, López and Ribeiro, among others, to problematize thought as linked to individual interest. We notice how much thought has been regarded as a problem-resolution tool in these documents, following a neoliberal logic that has been increasingly displaced from collective to individualized interest. Furthermore, the whole functioning of a disciplinary society is evident in the documents, as the latter moves towards a performance society, with greater emphasis on assessment practices and records of children’s “production.” We consider, both in the concept of childhood and the concept of experience, the possibility of experiencing other relationships with childhoods and temporalities in schools, and the power of both free time and play as open breathing spaces among routines that are both full of compulsory activities and empty of meaning.
The effect of multidrug-resistant organisms on social participation and quality of life in children with life-limiting conditions
Authors: Schmidt Pia , Hartenstein-Pinter Almut , Hasan Carola , Stening Kathrin , Zernikow Boris , Wager Julia 
Published: February 2021

Background: Children with life-limiting conditions have a high risk of colonisation with a multidrug-resistant organism (MDRO). To avoid the spread of hospital-aquired infections to other patients, children with a MDRO are moved to an isolated room or ward. However, such isolation prevents social participation, which may reduce the child's quality of life (QoL). To overcome this challenge of conflicting interests on a paediatric palliative care inpatient unit, a hygiene concept for patients colonised with MDRO, called PALLINI, was implemented. PALLINI advises that, instead of isolating the affected children, strict barrier nursing should be used. Aim: To identify the impact of a complex hygiene concept on children's and parents' QoL and social participation. Methods: Cross-sectional mixed-methods research approach, comprising semi-structured interviews with parents and staff members, and a QoL-questionnaire focusing on the child which was completed by parents. Findings: In paediatric patients with life-limiting conditions who have MDRO colonisation, using a complex hygiene protocol resulted in both benefits and barriers to social participation. However, the child's QoL did not appear to be affected. Conclusion: All staff members and families have to be familiar with the hygiene concept and the concept has to be self-explanatory and easy to apply.
Children's palliative care: examination of a nursing rotation programme
Authors: Whiting Lisa , Whiting Mark , Petty Julia , O'Grady Michele 
Published: February 2021

Background: An 8-month rotation programme was implemented for five nurses employed in two kinds of children's palliative care environments: hospital wards and hospices. This study reports the views of the nurses completing the rotation. The research drew on appreciative inquiry and involved a pre- and post-rotation interview and questionnaire. Thematic analysis of the interviews revealed seven themes: adjusting to the rotation programme; support mechanisms; being safe; new knowledge and skills; knowledge exchange; misconceptions; future plans. These were supported by the questionnaire findings. Although the nurses identified some frustration at having to undertake competency assessments relating to previously acquired skills, as well as being out of their ‘comfort zone’, all the participants highly recommended the programme. They commented very positively on the support they received and the overall learning experience as well as the new insight into different aspects of care. In addition, they were able to share their newfound knowledge and expertise with others.
Prognostic factors, symptoms and consequences of dehydration and dyselectrolytemia in patients with terminal stomach cancer
Authors: Bryniarski Paweł , Bryniarska Magdalena , Jezioro Maciej , Andrysiak Daniel , Filipczak-Bryniarska Iwona 
Published: February 2021

Background: Dyselectrolytaemia and dehydration are common symptoms in people with terminal stomach cancer. Aims: To determine factors related to dyselectrolytemia and dehydration in patients with terminal stomach cancer. Methods: An analysis of 134 patients with terminal stomach cancer admitted to the palliative care unit was conducted, through an audit of the patients' medical records. The average age of women was 63.1 years and that of men was 64.9 years. Findings: Dehydrated patients were more likely to: have dyselectrolytaemia; have a higher PS scale score; be taking opioids as an analgesic; have a high sodium concentration; experience dyspnoea, constipation, nausea and vomiting during hospitalisation; and require glucocorticoids administration both during and before hospitalisation. Patients with dyselectrolytaemia were more likely to: be admitted to the palliative care unit from the emergency department; experience cachexia and dehydration during hospitalisation and constipation at discharge; have a lower albumin level; and have a higher glucose level. Patients with dyselectrolytaemia also had a shorter duration of treatment and a 2.48 greater chance for death compared with those who did not have it. Conclusions: Knowledge of the adverse factors connected with dehydration and dyselectrolytaemia will allow health professionals to avoid dangerous clinical symptoms and prolong the life of those with terminal stomach cancer, as they might be able to foresee the occurrence of these conditions based on the medication the patient has been taking and symptoms they have been experiencing. Nurses will have a greater understanding of the importance of fluid therapy to resolve ionic disturbances and the need to address dehydration and dyselectrolytemia as a means to prolong and improve quality of life.