bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of androgens on Sertoli cell maturation in human testis from birth to puberty
Authors: Lapoirie Marion , Dijoud Frederique , Lejeune Hervé , Plotton Ingrid
Published: December 2021

Background

Androgens are well known to be necessary for spermatogenesis. The purpose of this study was to determine Sertoli cell responsiveness to androgens according to age from birth to puberty.

Results

Testicular tissue samples were studied in a population of 84 control boys classified into seven groups according to age:group 1 (1–30 days), group 2 (1–3 months), group 3 (3–6 months), group 4 (0.5–3 years), group 5 (3–6 years), group 6 (6–12 years), and group 7 (12–16 years). We compared these data with those of 2 situations of pathology linked to androgens: 1/premature secretion of testosterone: 4 cases of Leydig cell tumor (LCT) in childhood; and 2 /defect of androgen receptors (AR): 4 cases of complete form of insensitivity to androgen syndrome (CAIS). In control boys, AR immunoreactivity (ir) in Sertoli cells appeared between 4.6 and 10.8 years of age, Anti-Mullerian Hormone (AMH) ir in Sertoli cells disappeared between 9.2 and 10.2 years of age. Connexin 43 (Cx43) ir in Sertoli cells and histological features of the onset of spermatogenesis appeared between 10.8 and 13,8 years of age. Cx43 ir was significantly higher in 12–16 year-olds than in younger boys. In case of CAIS, no spermatogenesis was observed, both AR and Cx43 ir were undetectable and AMH ir was elevated in Sertoli cells even at pubertal age. In the vicinity of LCTs, spermatogenesis occurred and both AR and Cx43 ir were strongly positive and AMH ir in Sertoli cells was low for age.

Conclusions

Androgen action on Sertoli cells is required for onset of spermatogenesis and premature androgen secretion by LCT can induce spermatogenesis in the vicinity of the tumor. AR ir appeared earlier than onset of spermatogenesis, with large interindividual variability. The timing and mechanisms of Sertoli cell responsiveness to androgens are important issues for understanding the induction of spermatogenesis at puberty.
gcMECM: graph clustering of mutual exclusivity of cancer mutations
Authors: Hu Ying , Yan Chunhua , Chen Qingrong , Meerzaman Daoud
Published: December 2021

Background

Next-generation sequencing platforms allow us to sequence millions of small fragments of DNA simultaneously, revolutionizing cancer research. Sequence analysis has revealed that cancer driver genes operate across multiple intricate pathways and networks with mutations often occurring in a mutually exclusive pattern. Currently, low-frequency mutations are understudied as cancer-relevant genes, especially in the context of networks.

Results

Here we describe a tool, gcMECM, that enables us to visualize the functionality of mutually exclusive genes in the subnetworks derived from mutation associations, gene–gene interactions, and graph clustering. These subnetworks have revealed crucial biological components in the canonical pathway, especially those mutated at low frequency. Examining the subnetwork, and not just the impact of a single gene, significantly increases the statistical power of clinical analysis and enables us to build models to better predict how and why cancer develops.

Conclusions

gcMECM uses a computationally efficient and scalable algorithm to identify subnetworks in a canonical pathway with mutually exclusive mutation patterns and distinct biological functions.
Effectiveness of joint 3 + 1 malaria strategy along China–Myanmar cross border areas
Authors: Lin Zu-rui , Li Shi-gang , Sun Xiao-dong , Guo Xiang-rui , Zheng Zhi , Yang Jie , Pian Hong-ru , Tian Peng , Chen Qi-yan , Sun Xiao-ying , Ding Chun-li , Duan Kai-xia , Chen Hong-wei , Bee Dakhidam Yaw , Zhou Hong-ning
Published: December 2021

Background

Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted.

Methods

A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy.

Results

In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = − 1.18, P value = 0.24).

Conclusion

The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.
Rare case of Proteus mirabilis native mitral valve endocarditis in an immunocompromised patient
Authors: Grossman Lindsay G. , Sharkey Joseph M. , Grossman David S. , Hartman Alan , Makaryus Mina , Shah Kaushal B.
Published: December 2021

Background

Bacterial infective endocarditis caused by Proteus mirabilis is rare and there are few cases in the literature. The natural history and treatment of this disease is not as clear but presumed to be associated with complicated urinary tract infection (cUTI).

Case presentation

A 65-year-old female with a history of rheumatoid arthritis, factor V Leiden hypercoagulability, and prior saddle pulmonary embolism presented to the emergency department following a mechanical fall. Computed Tomography showed evidence of acute/subacute splenic emboli. Complicated UTI was likely secondary to a ureteral stone. Blood and urine cultures also grew out P. mirabilis. Transthoracic echocardiography revealed a mobile echogenic density on the anterior mitral valve (MV) leaflet consistent with a vegetation. The patient underwent MV replacement, and P. mirabilis was isolated from the surgically removed valve.

Conclusions

We hypothesize that the patient’s immunocompromised status following steroid and Janus Kinase inhibitor usage for rheumatoid arthritis contributed to Gram-negative bacteremia following P. mirabilis UTI, ultimately seeding the native MV. Additional studies with larger numbers of Proteus endocarditis cases are needed to investigate an association between immunosuppression and Proteus species endocarditis.
Predisposing factors to acquisition of acute respiratory tract infections in the community: a systematic review and meta-analysis
Authors: Hammond Ashley , Halliday Alice , Thornton Hannah V. , Hay Alastair D.
Published: December 2021

Background

Preventing respiratory tract infections (RTIs) could have profound effects on quality of life, primary care workload, antibiotic prescribing and stewardship. We aimed to identify factors that increase and decrease RTI acquisition within Organisation for Economic Cooperation and Development (OECD) member countries.

Methods

Systematic search of Medline, Embase, Cochrane and ISI Web of Knowledge for studies conducted up to July 2020 reporting predisposing factors for community RTI acquisition. Pooled odds ratios were calculated using a random-effects model.

Results

23 studies investigated risk factors associated with community-acquired pneumonia (n = 15); any RTI (n = 4); influenza like illness (n = 2); and lower RTI (n = 2). Demographic, lifestyle and social factors were: underweight BMI (pooled odds ratio (ORp 2.14, 95% CI 1.58 to 2.70, p = 0.97); male sex (ORp 1.30, 95% CI 1.27 to 1.33, p = 0.66); contact with pets (ORp 1.35, 95% CI 1.16 to 1.54, p = 0.72); contact with children (ORp 1.35, 95% CI 1.15 to 1.56, p = 0.05); and ex-smoking status (ORp 1.57, 95% CI 1.26 to 1.88, p = 0.76). Health-related factors were: chronic liver condition (ORp 1.30, 95% CI 1.09 to 1.50, p = 0.34); chronic renal condition (ORp 1.47, 95% CI 1.09 to 1.85, p = 0.14); and any hospitalisation in previous five years (ORp 1.64, 95% CI 1.46 to 1.82, p = 0.66).

Conclusions

We identified several modifiable risk factors associated with increased likelihood of acquiring RTIs in the community, including low BMI, contact with children and pets. Modification of risk factors and increased awareness of vulnerable groups could reduce morbidity, mortality and antibiotic use associated with RTIs.

PROSPERO registration

CRD42019134176.
Validation of the intolerance of uncertainty scale as a screening tool for perinatal anxiety
Authors: Furtado Melissa , Frey Benicio N. , Green Sheryl M.
Published: December 2021

Background

To date, there is a significant lack of research validating clinical tools for early and accurate detection of anxiety disorders in perinatal populations. Intolerance of uncertainty was recently identified as a significant risk factor for postpartum anxiety symptoms and is a key trait of non-perinatal anxiety disorders. The present study aimed to validate the Intolerance of Uncertainty Scale (IUS) in a perinatal population and evaluate its use as a screening tool for anxiety disorders.

Methods

Psychiatric diagnoses were assessed in a sample of perinatal women (n = 198), in addition to completing a self-report battery of questionnaires. Psychometric properties including internal consistency and convergent and discriminant validity were assessed. Determination of an optimal clinical cut-off score was measured through a ROC analysis in which the area under the curve, sensitivity, specificity, as well as positive and negative predictive values were calculated.

Results

The IUS demonstrated excellent internal consistency (α = 0.95) and an optimal clinical cut-off score of 64 or greater was established, yielding a sensitivity of 89%. The IUS also demonstrated very good positive (79%) and negative (80%) predictive values.

Conclusions

These findings suggest that the IUS represents a clinically useful screening tool to be used as an aid for the early and accurate detection of perinatal anxiety.
The psychological impact of paediatric burn injuries: a systematic review
Authors: Woolard Alix , Hill Nicole T. M. , McQueen Matthew , Martin Lisa , Milroy Helen , Wood Fiona M. , Bullman Indijah , Lin Ashleigh
Published: December 2021

Objective

To review and synthesise qualitative literature regarding the psychological outcomes following paediatric burn injuries, and to determine if children and adolescents who experience a burn injury have elevated risk of psychopathology following the injury.

Design

Systematic review of quantitative and qualitative studies.

Data sources

Informit health, Medline, Embase, and PsycINFO were searched from January 2010 to December 2020.

Data extraction and synthesis

Two reviewers screened articles, and one reviewer extracted data (with cross-checking from another reviewer) from the included studies and assessed quality using an established tool. Narrative synthesis was used to synthesise the findings from the quantitative studies, and thematic synthesis was used to synthesise the findings of included qualitative studies.

Results

Searches yielded 1240 unique titles, with 130 retained for full-text screening. Forty-five studies from 17 countries were included. The psychological outcomes included in the studies were mental health diagnoses, medication for mental illness, depression, anxiety, stress, fear, post-traumatic stress, post-traumatic growth, emotional issues, self-harm, self-esteem, self-concept, stigmatisation, quality of life, level of disability, resilience, coping, and suicidality.

Conclusions

Our findings highlight paediatric burn patients as a particularly vulnerable population following a burn injury. Studies suggest elevated anxiety and traumatic stress symptoms, and higher rates of psychopathology in the long-term. Further research is recommended to determine the psychological outcomes in the other mental health domains highlighted in this review, as findings were mixed.

Clinical care teams responsible for the aftercare of burn patients should involve psychological support for the children and families to improve outcomes.
Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade
Authors: Ding Yin , Tang Xuanli , Wang Yuhui , Yu Dongrong , Zhu Caifeng , Yu Jin
Published: December 2021

Background

Podocytes have become a crucial target for interventions in proteinuric kidney diseases. Many studies have reported that overexpression of transient receptor potential cation channel protein 6 (TRPC6) in podocyte injury upregulates intracellular Ca2+ influx and stimulates Ca2+-dependent protease calpain-1 signaling. The traditional Chinese drug, tetrandrine, a nonselective Ca2+ channel blocker, has long been used to treat chronic kidney disease. This research aimed to explore the possible mechanisms underlying the anti-proteinuric properties of tetrandrine.

Methods

We investigated the involvement of tetrandrine in Ca2+ dependent calpain-1 signaling in mouse podocytes and adriamycin-induced nephropathy rats. Cyclosporine A (CsA) and U73122 were used as positive controls. Cell viability, cytotoxicity, Ca2+ concentration, calpain activity, and mRNA and protein expression levels of calpain-1 signaling pathways were examined. The clinical and pathological changes were measured.

Results

Tetrandrine decreased intracellular Ca2+ influx in cultured TRPC6-overexpressing podocytes. In both in vitro and in vivo studies, the administration of tetrandrine downregulated calpain activity and the expression of calpain-1 and restored the expression of downstream Talin-1 and nephrin. Compared to CsA, tetrandrine treatment exhibited superior inhibitory effects on calpain activity and calpain-1 expression.

Conclusions

Tetrandrine has therapeutic potential in podocyte damage by blocking Ca2+-dependent activation of the calpain-1 signaling pathway. Tetrandrine reduced proteinuria, improved renal function, and alleviate renal pathological damage.
Protein expression of the tear film of domestic cats before and after inoculation with Toxoplasma gondii
Authors: Guedes Paula Elisa Brandão , Veloso Jéssica Fontes , Lacerda Luciana Carvalho , Santana Juliano Oliveira , Mora-Ocampo Irma Yuliana , Pirovani Carlos Priminho , Cruz Rebeca Dalety Santos , Munhoz Alexandre Dias , Carlos Renata Santiago Alberto
Published: December 2021

Background

Tear film (TF) helps maintain and protect ocular function against damage to the ocular surface. Proteins are one of its main constituents, whose expression pattern can be used as a biomarker of ocular changes and systemic diseases. The aim of this study was to evaluate the expression of proteins in the TF of domestic cats before and after infection with Toxoplasma gondii, in the phases of acute infection and chronicity. Twelve healthy cats received orally homogenized brain matter obtained from mice inoculated with T. gondii oocysts, strain ME49. Cat feces were collected daily from the third day after infection to assess the release of oocysts. TF samples were obtained from cats, by Schirmer’s Tear Test 1, on day 0 (before infection), day 5 after infection (acute phase of infection, with maximum peak release of oocysts in feces) and on day 21 after infection (start of chronic phase, 7 days after total absence of oocyst release in feces). Tear samples were also submitted to proteomic analysis in a Q-Tof-Premier mass spectrometer.

Results

A total of 37 proteins with scores equal to or greater than 100 were identified on D0, followed by 36 on D5 and 42 on D21. Of these, 27 were common to D0 and D5, 33 to D0 and D21, 27 to D5 and D21, and 26 were common to the three groups, totaling 54 proteins. The most abundant proteins were lipocalin allergen Fel d, serum albumin, aldehyde dehydrogenase, lactoperoxidase and lactotransferrin. There was no significant difference in the abundance of proteins found on D0 and D5, but there was a statistical difference between D0 and D21 for ACT1_AEDAE, CERU_HUMAN and GELS_HUMAN. Regarding D5 and D21, there were significant differences for KV1_CANLF, LAC_PIG, TRFL_PIG, ACT1_AEDAE, CERU_HUMAN, GELS_HUMAN and OVOS2_HUMAN.

Conclusions

The main proteins identified in the TF of domestic cats are similar to those found in humans and other animal species. Most are part of the ocular surface defense system against injuries. The most expressed proteins in animals in the chronic phase of T. gondii infection are associated with the immune response to the parasite.
Prevalence and associated factors of gender based violence among Baso high school female students, 2020
Authors: Mingude Alemu Basazin , Dejene Tadesse Mamo
Published: December 2021

Background

Gender-based violence (GBV) is a common reproductive health problem, especially in developing countries. It is still the first research priority area in Africa that is identified by World Health Organization. The main aim of this study was to identify the prevalence and determinants of Gender Based Violence among Baso high school female students in Debre Berhan town, Ethiopia.

Methods

An institutional based cross-sectional study was conducted in Debre Berhan, Ethiopia. A total of 350 female students were selected by stratified sampling technique. A self-administered structured questionnaire was used to collect the data. Each independent variable was fitted separately into bivariate logistic analysis, and Variables with p-values less than 0.25 in bivariable model were fitted into multivariate logistic regression analysis to evaluate the degree of association with gender-based violence. The significance level was obtained with 95% CI and p-value < 0.05.

Result

The prevalence of GBV during the lock- down was 36.2% (95% CI 0.3, 0.4), and the lifetime prevalence of GBV was 47.2% (95% CI 0.4, 0.5). The prevalence of life time sexual violence and physical violence were found to be 27.99% (95% CI 0.2, 0.3), and 37.99% (95% CI 0.3, 0.4), respectively. Sexual violence and physical violence during the lockdown were found to be 21.3% and 17.8%, respectively. Respondents educational performance (AOR = 4.5; 95% CI 1.8, 11.3), monthly pocket money received from their parents (AOR = 3; 95% CI 1.6, 5.6), free discussion about reproductive issue (AOR = 2.7; 95% CI 1.4, 5.2), and experience of sexual intercourse (AOR = 13.2; 95% CI 4.8, 36.4) were found to be associated factors of gender based violence.

Conclusion and recommendation

Gender Based Violence is still a significant sexual and reproductive health issue in Ethiopia. Governmental and non-governmental organizations should give due attention to this problem. Moreover, further large-scale studies are needed to estimate the national figure of GBV and to identify route causes.
Transmission of synovial sarcoma from a single multi-organ donor to three transplant recipients: case report
Authors: Zhang Jian , Yang Yang , Tian Ye , Xu Ruifang , Lin Jun
Published: December 2021

Background

Transmission of malignancy is a notable problem that cannot always be absolutely predicted at the time of transplantation. In particular, donor-derived transmission of synovial sarcoma in solid-organ transplantation is a rare but catastrophic event.

Case presentation

We are the first to report three cases of synovial sarcoma transmitted from a single multi-organ donor in China. The donor died of respiratory failure caused by an intrathoracic tumor, which was diagnosed as benign at the time of donation. All three recipients developed synovial sarcoma 3–13 months after transplantation; all three cases were confirmed to be donor transmitted. The liver transplant recipient died of tumor metastasis after partial-allograft hepatectomy. The two renal-transplant recipients survived after comprehensive therapy, including allograft nephrectomy, withdrawal of immunosuppressants and targeted therapy with anlotinib.

Conclusions

This report highlights the importance of detailed donor assessment, close follow-up and timely treatment of unexpected donor-transmitted malignancy. Although pathology is the most important evidence for the exclusion of donors for malignant potential, it should be combined with tumor type, tumor size and speed of growth. Organs from donors with malignant potential should be discarded. Allograft nephrectomy should be considered after confirmation of renal-allograft synovial sarcoma. Anlotinib for synovial sarcoma seems to be effective and well tolerated during long-term follow-up.
Prevalence of breastfeeding in a baby-friendly pediatric practice in Trieste, Italy: follow up to 36 months of age
Authors: Milinco Mariarosa , Cattaneo Adriano , Macaluso Anna , Materassi Paola , Di Toro Nicola , Ronfani Luca
Published: December 2021

Background

A breastfeeding-friendly physician’s office that applies the 13 recommendations of the Academy of Breastfeeding Medicine can help increase the exclusivity and duration of breastfeeding. Having already published the results up to five months of age of this intervention in our pediatric practice, we now report on the follow up to 36 months.

Methods

A cohort of 252 newborn infants was enrolled with our pediatric office in Trieste, Italy, between 1 January 2016 and 31 December 2016. The office implemented baby-friendly pediatric practices and a biological nurturing approach to the support of breastfeeding. In addition to the services offered by two pediatricians, support was provided by a peer counselor. Data on breastfeeding were collected at periodic healthy child visits up to 36 months of age. The outcome of interest for this follow up was the rate of any breastfeeding, defined as the percentage of infants and children who had received breastmilk in the previous 24 h.

Results

The rates of any breastfeeding at discharge and at 1, 3 and 5 months (n = 252) were 95.2, 95.8, 89.3 and 86.5%, respectively. At 8, 12, 18, 24 and 36 months of age, the rates of breastfeeding were 70.6% (163/231), 59% (135/229), 35% (78/224), 24.6% (55/224) and 7.2% (16/224), respectively.

Conclusions

The rates of any breastfeeding recorded in our pediatric practice up to age 36 months, are much higher than those reported elsewhere in high income countries and are likely to be associated with our baby-friendly and biological nurturing approach.
Multidisciplinary approach to screening and management of children with Fabry disease: practice at a Tertiary Children’s Hospital in China
Authors: Shen Qian , Liu Jialu , Chen Jing , Zhou Shuizheng , Wang Yi , Yu Lifei , Sun Li , Wang Liuhui , Wu Bingbing , Liu Fang , Cao Yun , Huang Ying , Wang Jianshe , Yang Chenhao , Zhu Daqian , Ma Yangyang , Xu Zhengmin , Lu Wei , Fu Lili , Zhou Wenhao , Xu Hong
Published: December 2021

Background

Fabry disease (FD) remains poorly recognized, especially in children in China. Considering the diversity and nonspecific clinical manifestations accompanying with life-threatening aspect of this disease, methods to improve effective screening and management of the suspects are needed. This study aims to explore how it can be done effectively from a multidisciplinary perspective for children with FD at a tertiary children’s hospital in China.

Methods

A multidisciplinary team (MDT) of pediatric FD experts was launched at Children’s Hospital of Fudan University. Children with high-risk characteristics were referred by the MDT screening team using the dried blood spot (DBS) triple-test (α-galactosidase A, globotriaosylsphingosine, GLA gene). For newborns who were undergoing genetic testing in the hospital, the GLA gene was listed as a routine analysis gene. Evaluation, family screening, and genetic counselling were implemented after screening by the MDT management team.

Results

Before the establishment of the MDT, no case was diagnosed with FD in the hospital. However, twelve months following the MDT program's implementation, thirty-five children with high-risk profiles were referred for screening by DBS triple-test, with a yield of diagnosis of 14.3% (5/35). These 5 diagnosed children were referred due to a high-risk profile of pain accompanied by dermatological angiokeratoma and hypohidrosis (n = 2), pain accompanied by abnormal liver function (n = 1), pain only (n = 1), and unexplained renal tubular dysfunction (n = 1). Two neonates were detected early with GLA mutations in the hospital, with a yield of detection of 0.14% (2/1420). Furthermore, another 3 children diagnosed with FD were referred from other hospitals. Family screening of these 10 diagnosed children indicated that 9 boys inherited it from their mothers and 1 girl inherited it from her father. Four of them started to receive enzyme replacement therapy.

Conclusion

Screening and management of children with FD is effective based on a defined screening protocol and a multidisciplinary approach. We should pay more attention to the high-risk profiles of pain, angiokeratoma, decreased sweating, and unexplained chronic kidney disease in children.
Clinical development innovation in rare diseases: lessons learned and best practices from the DevelopAKUre consortium
Authors: Rudebeck Mattias , Scott Ciarán , Rhodes Nicholas P. , van Kan Christa , Olsson Birgitta , Al-sbou Mohammed , Hall Anthony K. , Sireau Nicolas , Ranganath Lakshminarayan R.
Published: December 2021

New opportunities have arisen for development of therapies for rare diseases with the increased focus and progress in the field. However, standardised framework integrating individual initiatives has not been formed. We present lessons learned and best practice from a collaborative success case in developing a treatment for a rare genetic disease. Our unique consortium model incorporated several of the identified developments under one project, DevelopAKUre, truly bringing together academia, industry and patient organisations in clinical drug development. We found that the equal partnership between all parties in our consortium was a key success factor creating a momentum based on a strong organisational culture where all partners had high engagement and taking ownership of the entire programme. With an agreed mutual objective, this provided synergies through connecting the strengths of the individual parties. Another key success factor was the central role of the patient organisation within the management team, and their unique study participants’ advocacy role securing the understanding and meeting the needs of the clinical study participants in real-time. This resulted in an accelerated enrolment into the clinical studies with a high retention rate allowing for delivery of the programme with significantly improved timelines. Our project was partly funded through an external EU research grant, enabling our model with equal partnership. Further attention within the community should be given to establishing a functional framework where sustainable funding and risk sharing between private and public organisations allow for our model to be replicated.
Mobile clinics in conflict-affected communities of North West and South West regions of Cameroon: an alternative option for differentiated delivery service for internally displaced persons during COVID-19
Authors: Omam Lundi-Anne , Jarman Elizabeth , Ekokobe Wilfred , Evon Agbor , Omam Esther Njomo
Published: December 2021

Introduction

The guidelines for differentiated service delivery (DSD) for HIV treatment became operational in Cameroon in 2017 with the Test and Treat national strategy elaborating services that can be decentralized and task shifted at community level, but with little to no guidelines for DSD in fragile and conflict-affected settings. Since 2016, more than 680,000 Cameroonians have been internally displaced due to the conflict in the North West and South West regions (NWSW). This conflict has impacted on the health system with numerous attacks on health facilities and staff, reducing access to health care for internally displaced persons. The outbreak of COVID-19 further reduced humanitarian responses for fear of spreading COVID-19. Mobile clinics were utilized as a model of care in piloting DSD for HIV in conflict-affected settings within the COVID-19 context.

Methods

The HIV DSD framework was used to evaluate a project that used mobile clinics in 05 divisions across the NWSW to provide primary health care to internally displaced persons in hard-to-reach areas. These mobile clinics were operated in the COVID-19 context and integrated HIV services in the benefit package. The mobile clinics mainstreamed HIV and COVID-19 sensitization during community mobilization, HIV consultations, HIV testing and referrals, and in some cases antiretroviral (ARV) dispensation. The project ran from March to October 2020. The results from the evaluation of this model of HIV care delivery were analysed in 06 of 08 mobile clinics.

Results

In 07 months, a total of 14,623 persons living in conflict-affected settings were sensitized on HIV, 1979 received HIV testing from which 122 were positive and 33 placed on ARVs. 28 loss-to-follow up people living with HIV were relinked to treatment and 209 consultations for persons living with HIV were conducted. Despite the good collaboration at regional and field level, there was distrust by ARV centers for humanitarian organizations.

Conclusion

Mobile clinics are a model of care which could be leveraged in fragile and conflict-affected settings as an alternative model of care for HIV DSD to ensure continuum of HIV care and treatment. However this should be integrated within the benefit package of primary health care services offered by mobile clinics.
The impact of armed conflict on utilisation of health services in north-west Syria: an observational study
Authors: Ekzayez Abdulkarim , Alhaj Ahmad Yasser , Alhaleb Hasan , Checchi Francesco
Published: December 2021

Background

Armed conflicts are known to have detrimental impact on availability and accessibility of health services. However, little is known on potential impact on utilisation of these services and health seeking behaviour. This study examines whether exposure to different types of war incidents affected utilisation of key health services—outpatient consultations, antenatal care, deliveries, and C-sections, in conflict affected areas of north west Syria between 1 October 2014 and 30 June 2017.

Methods

The study is an observational study using routinely collected data of 597,675 medical consultations and a database on conflict incidents that has 11,396 events. Longitudinal panel data analysis was used with fixed effect negative binomial regression for the monthly analysis and distributed lag model with a lag period of 30 days for the daily analysis.

Results

The study found strong evidence for a negative association between bombardments and both consultations and antenatal care visits. The monthly Risk Ratio was 0.95 (95% CI 0.94–0.97) and 0.95 (95% CI 0.93–0.98); and the cumulative daily RR at 30 days was 0.19 (95% CI 0.15–0.25) and 0.42 (95% CI 0.25–0.69) for consultations and antenatal care respectively. Explosions were found to be positively associated with deliveries and C-sections. Each one unit increase in explosions in a given month in a given village was associated with about 20% increase in deliveries and C-sections; RR was 1.22 (95% CI 1.05–1.42) and 1.96 (95% CI 1.03–3.74) respectively.

Conclusion

The study found that access to healthcare in affected areas in Syria during the study period has been limited. The study provides evidence that conflict incidents were associated negatively with the utilisation of routine health services, such as outpatient consultations and antenatal care. Whereas conflict incidents were found to be positively associated with emergency type maternity services—deliveries, and C-sections.
Bullying at school and mental health problems among adolescents: a repeated cross-sectional study
Authors: Källmén Håkan , Hallgren Mats
Published: December 2021

Objective

To examine recent trends in bullying and mental health problems among adolescents and the association between them.

Method

A questionnaire measuring mental health problems, bullying at school, socio-economic status, and the school environment was distributed to all secondary school students aged 15 (school-year 9) and 18 (school-year 11) in Stockholm during 2014, 2018, and 2020 (n = 32,722). Associations between bullying and mental health problems were assessed using logistic regression analyses adjusting for relevant demographic, socio-economic, and school-related factors.

Results

The prevalence of bullying remained stable and was highest among girls in year 9; range = 4.9% to 16.9%. Mental health problems increased; range = + 1.2% (year 9 boys) to + 4.6% (year 11 girls) and were consistently higher among girls (17.2% in year 11, 2020). In adjusted models, having been bullied was detrimentally associated with mental health (OR = 2.57 [2.24–2.96]). Reports of mental health problems were four times higher among boys who had been bullied compared to those not bullied. The corresponding figure for girls was 2.4 times higher.

Conclusions

Exposure to bullying at school was associated with higher odds of mental health problems. Boys appear to be more vulnerable to the deleterious effects of bullying than girls.
Is the clinical pattern of pediatric celiac disease changing? A thirty-years real-life experience of an Italian center
Authors: Pedretti Melissa , Sbravati Francesca , Allegri Davide , Labriola Flavio , Lombardo Virginia , Spisni Enzo , Zarbo Chiara , Alvisi Patrizia
Published: December 2021

Objectives

Clinical presentation of pediatric celiac disease (CD) is heterogeneous and ever-evolving. Our aim is to highlight its changes throughout the years.

Methods

Data about clinical presentation of CD in children diagnosed between 1990 and 2020 at the CD Center of Maggiore Hospital, Bologna, were collected. Patients were stratified into groups based on the date [P1 (1990–2011), P2 (2012–2020)] and age [G1 (< 2 years), G2 (2–5), G3 (6–11), G4 (12–18)] at diagnosis, then investigated by comparing CD clinical presentation in different periods and ages.

Results

1081 children were selected. Mean age at diagnosis increases from 5.9 to 6.6 years from P1 to P2. Gastrointestinal Symptoms (GIs) are predominant, with a decline of diarrhea (47%VS30%) and an increase of constipation (4%VS19%) (p < 0.001). Among Extraintestinal symptoms (EIs) a decrease of anemia (76%VS43%, p = 0,001) is observed. Failure to Thrive (FTT) is stable throughout the years (p = 0.03), while screenings show a trend of increment (19%VS23%). GIs’ frequency decline from G1 to G4 (p = 0,001), with reduction of diarrhea (p < 0.001), and rise of recurrent abdominal pain (p = 0,02). EIs are more frequent at older ages, FTT in younger patients.

Conclusions

Changes in clinical presentation of CD have occurred in the last 30 years. We observe a reduction of severe and classic gastroenterologic symptoms and a rise of atypical ones, together with a growth of serological screenings and higher age at diagnosis. Awareness about CD clinical trends is crucial for a proper approach and early diagnosis.
Diagnostic challenges of an incidental finding: case report of definitely-congenital glioblastoma multiforme in a very preterm infant
Authors: Martini Silvia , Paoletti Vittoria , Maffei Monica , Zucchelli Mino , Locatelli Chiara , Fischer Maximilian , Fabbri Viscardo Paolo , Foschini Maria Pia , Tallini Giovanni , Corvaglia Luigi
Published: December 2021

Background

Congenital brain tumors are extremely rare in the neonatal population, and often associated with a poor prognosis. The diagnostic suspicion is often aroused at antenatal scans or postnatally, if clinical signs and symptoms of increased intracranial pressure become evident. We present a case of definitely congenital glioblastoma multiforme incidentally diagnosed in a preterm infant, aiming to raise clinical awareness on this condition and to highlight the challenges of the related diagnostic work-up.

Case presentation

This female infant was born at 31 weeks’ gestation after an uneventful pregnancy. No abnormalities were detected at antenatal ultrasound scans and genetic tests. Head circumference at birth was on the 25th centile. A routine brain ultrasound scan performed on day 1 revealed a large, inhomogeneous lesion in the right cerebral hemisphere, with contralateral midline shift, which was confirmed by brain magnetic resonance imaging (MRI). Eye fundus and routine blood exams, including platelets count, coagulation screening and C-reactive protein, were normal.

Given the high risk of complications, surgical biopsy of the lesion was temporarily hold and a daily sonographic follow-up was undertaken. Although head circumference growth was steady on the 25th centile, progressive changes of the lesion were detected by cranial ultrasound.

The repeat MRI scans showed a significant enlargement of the mass, with contralateral midline shift and signs of intralesional and intraventricular bleeding. In view of this worsening, surgical resection was performed. The histological examination of the lesion biopsy documented a GFAP+ highly cellular neoplasm, with no mutation on SMARCB1 gene. At the molecular analysis, mutations on IDH and H3F3A genes were absent, whereas MGMT promoter was unmethylated. The diagnosis was grade IV glioblastoma IDH wild-type.

Conclusions

Congenital glioblastoma multiforme is an extremely rare but highly aggressive neoplasm. Since intralesional biopsy is not often feasible in affected neonates, knowledge of the associated clinical and neuroradiological features is particularly important, as they can also add useful information on the neoplasm behavior. Specimens from open surgical resection allow to perform a definite histological analysis and an extended molecular characterization, with relevant prognostic implications.
Prevalence of germline TP53 mutation among early onset middle eastern breast cancer patients
Authors: Siraj Abdul Khalid , Masoodi Tariq , Bu Rong , Parvathareddy Sandeep Kumar , Iqbal Kaleem , Azam Saud , Al-Rasheed Maha , Ajarim Dahish , Tulbah Asma , Al-Dayel Fouad , Al-Kuraya Khawla Sami
Published: December 2021

Background

The data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited.

Methods

We determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing.

Results

Germline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS.

Conclusions

TP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.
Disablement in the Physically Active Scale Short Form-8: psychometric evaluation
Authors: Casanova Madeline P. , Nelson Megan C. , Pickering Michael A. , Larkins Lindsay W. , Appleby Karen M. , Grindley Emma J. , Baker Russell T.
Published: December 2021

Background

Patient-centered care and evidence-based practice (EBP) are core competencies for health care professionals. The importance of EBP has led to an increase in research involving clinical outcomes; current recommendations emphasize collecting patient focused measures, thus increasing the need for psychometrically sound patient reported outcome measures (PROMs) of health. Disablement has been identified as a valuable multi-dimensional construct for patient care. The Disablement in the Physically Active Scale Short Form-8 (DPA SF-8) has been proposed as a tool to be used in the physically active population that assesses a physical summary component of health and a quality of life component however, further analysis is necessary to ensure the instrument is psychometrically sound.

Methods

Confirmatory factor analyses (CFAs) were conducted on the DPA SF-8 at each time point to ensure factor structure. Reliability of the scale and internal consistency of the subscales were assessed, and a minimal detectable change (MDC) calculated. Additionally, a minimal clinically important difference (MCID) was also established, and invariance testing across three time points and groups was conducted.

Results

The CFAs at all three visits exceeded recommended model fit indices. The interclass correlation coefficient value (.924) calculated indicated excellent scale reliability and Cronbach’s alpha for subscales PHY and QOL were within recommend values. The MDC value calculated was 5.83 and the MCID for persistent injuries were 2 points and for acute injuries, 3 points. The DPA SF-8 was invariant across time and across subgroups.

Conclusions

The DPA SF-8 met CFA recommendations and criteria for multi-group and longitudinal invariance testing, which indicates the scale may be used to assess for differences between the groups or across time. Our overall analysis indicates the DPA SF-8 is a valid, reliable, and responsive instrument to assess patient improvement in the physically active population.
Reproducibility and research integrity: the role of scientists and institutions
Authors: Diaba-Nuhoho Patrick , Amponsah-Offeh Michael
Published: December 2021

Reproducibility and research integrity are essential tenets of every scientific study and discovery. They serve as proof that an established and documented work can be verified, repeated, and reproduced. New knowledge in the biomedical science is built on the shoulders of established and proven principles. Thus, scientists must be able to trust and build on the knowledge of their colleagues. Scientific innovation and research discoveries especially in the field of medicine has contributed to improving the lives of patients and increasing life expectancies. However, the growing concerns of failure to comply with good scientific principles has resulted in issues with research integrity and reproducibility. Poor reproducibility and integrity, therefore, may lead to ineffective interventions and applications. Here we comment on research reproducibility in basic medical and life sciences with regards to issues arising and outline the role of stakeholders such as research institutions and their employees in addressing this crisis.
Evidence of an active Cushing reflex in a preterm neonate with hyaline membrane disease: a case report
Authors: Rothberg Alan D. , Smith Johan , Lubbe Welma
Published: December 2021

Background

The Cushing reflex does not appear to have been described in preterm neonates. This case report shows the presence of an active Cushing reflex in a 32-week preterm neonate with hyaline membrane disease.

Case presentation

The 1.94 kg Caucasian infant was delivered by caesarean section following concerns about possible maternal infection and fetal compromise. Chest X-ray showed mild-to-moderate hyaline membrane disease and treatment was initiated with supplemental oxygen and nasal continuous positive airway pressure. It is probable that a pneumothorax occurred at 5–6 hours of age, with progression during the day. Interstitial air, pneumomediastinum, and tension pneumothorax were diagnosed on subsequent X-ray, and ultrasound of the brain showed a grade IV intraventricular hemorrhage. A review of the nurses’ recordings of heart rate, blood pressure, and respiratory rate showed a progressive increase in blood pressure accompanied by slowing of the heart rate and irregular respiration. These are features of the Cushing reflex that is elicited in response to raised intracranial pressure.

Conclusion

While well-described in older children and adults, in neonates the Cushing reflex has mainly been described in animal experiments and infants who have developed hydrocephalus. It is likely that in this case, the reflex was elicited as a result of a progressive increase in intracranial pressure due to the combination of elevated intrathoracic pressure, obstructed venous return from the brain, and concurrent intraventricular hemorrhage.
Magnetic nanoparticles in theranostics of malignant melanoma
Authors: Shevtsov Maxim , Kaesler Susanne , Posch Christian , Multhoff Gabriele , Biedermann Tilo
Published: December 2021

Malignant melanoma is an aggressive tumor with a tendency to metastasize early and with an increasing incidence worldwide. Although in early stage, melanoma is well treatable by excision, the chances of cure and thus the survival rate decrease dramatically after metastatic spread. Conventional treatment options for advanced disease include surgical resection of metastases, chemotherapy, radiation, targeted therapy and immunotherapy. Today, targeted kinase inhibitors and immune checkpoint blockers have for the most part replaced less effective chemotherapies. Magnetic nanoparticles as novel agents for theranostic purposes have great potential in the treatment of metastatic melanoma. In the present review, we provide a brief overview of treatment options for malignant melanoma with different magnetic nanocarriers for theranostics. We also discuss current efforts of designing magnetic particles for combined, multimodal therapies (e.g., chemotherapy, immunotherapy) for malignant melanoma.