bluuebunny/crossref_metadata_2025 huggingface dataset:
C-reactive protein/albumin ratio and Glasgow prognostic score are associated with prognosis and infiltration of Foxp3+ or CD3+ lymphocytes in colorectal liver metastasis
Authors: Kanno Hiroki , Hisaka Toru , Akiba Jun , Hashimoto Kazuaki , Fujita Fumihiko , Akagi Yoshito
Published: August 2022

Background

Inflammatory indices and tumor-infiltrating lymphocytes (TILs) have prognostic value in many cancer types. This study aimed to assess the prognostic value of inflammatory indices and evaluate their correlation with survival and presence of TILs in patients with colorectal liver metastasis (CRLM).

Methods

Medical records of 117 patients who underwent hepatectomy for CRLM were retrospectively reviewed. We calculated inflammatory indices comprising the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, C-reactive protein/albumin ratio (CAR), and Glasgow prognostic score (GPS). Furthermore, we evaluated the relationship between these ratios and the GPS and survival rates and immunohistochemical results of tumor-infiltrating CD3+, CD8+, and Foxp3+ lymphocytes.

Results

The patients with low CAR values and low GPS had significantly better overall survival as per the log-rank test (p = 0.025 and p = 0.012, respectively). According to the multivariate analysis using the Cox proportional hazard model, the CAR (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.33–0.99; p = 0.048) and GPS (HR, 0.40; 95% CI, 0.19–0.83; p = 0.013) were independent prognostic factors. Additionally, Foxp3+ lymphocytes were more common in samples from the patients with a low CAR (p = 0.041). Moreover, the number of CD3+ TILs was significantly higher in the patients with a low GPS (p = 0.015).

Conclusions

The CAR and GPS are simple, inexpensive, and objective markers associated with predicting survival in patients with CRLM. Moreover, they can predict the presence of Foxp3+ and CD3+ lymphocytes in the invasive margin of a tumor.

Trial registration

Retrospectively registered. https://www.kurume-u.ac.jp/uploaded/attachment/14282.pdf.
Prevalence and sociodemographic factors associated with polysubstance use: analysis of a population-based survey in Jamaica
Authors: Lalwani Kunal , Whitehorne-Smith Patrice , Walcott Geoffrey , McLeary Joni-Gaye , Mitchell Gabrielle , Abel Wendel
Published: July 2022

Background

In Latin America and the Caribbean, there is a dearth of research exploring polysubstance use. This study aims to determine the prevalence, varying combinations and associated sociodemographic characteristics of polysubstance use in Jamaica.

Methods

This study involved a secondary data analysis of the Jamaica National Drug Prevalence Survey 2016 dataset where 4,623 participants between the age of 12 and 65 years from each household were randomly selected as respondents. Statistical analysis was performed to determine the prevalence and the sociodemographic correlates of polysubstance use among Jamaicans.

Results

19.6% of respondents used two or more drugs in their lifetime. Of this amount 68.7% reported past year use and 61.9% reported past month use. Bivariate analyses reported polysubstance use was statistically significantly higher amongst males (U = 54,579,p = 0.000), those living in rural areas (U = 91,892,p = 0.003), non-Christian (U = 89,514,p = 0.014), and married persons (U = 74,672,p = 0.000). Past month polysubstance use was statistically significantly higher among employed persons than unemployed persons were (U = 81,342,p = 0.001). Surprisingly, there was a lack of significant differences between education level, household income and past month concurrent polysubstance use (p = 0.609;p = 0.115 respectively). Logistic regression model indicated males were 3.076 times more likely than females to report past month polysubstance use than females. Also, when compared to those 55–65 years old, participants 35–54 years were 2.922 times more likely and those 18–34 years were 4.914 times more likely to report past month polysubstance use. Additionally, those living in rural areas were 1.508 times more likely than participants living in urban areas to report past month polysubstance use. As it relates to occupational status, when compared to armed forces, skilled workers were 4.328 times more likely and unskilled workers were 7.146 times more likely to report past month polysubstance use.

Conclusions

One in five Jamaicans identified as polysubstance users, predominated by marijuana as the most common factor amongst the polysubstance combinations examined, signalling the need for early marijuana interventions.
A 34-year overview of night work by occupation and industry in France based on census data and a sex-specific job-exposure matrix
Authors: Houot Marie-Tülin , Tvardik Nastassia , Cordina-Duverger Emilie , Guénel Pascal , Pilorget Corinne
Published: July 2022

Background

Night work has been increasing in the last decades due to new working arrangements for good and services production. Numerous studies have shown that night shift work causes disruptions in circadian rhythms that may affect health. In 2019, night shift work was classified as probably carcinogenic to humans by the International Agency for Research on Cancer, and may contribute to other health disorders. In this context, we assessed the number and proportion of workers exposed to night work today and investigated time trends by occupation and industry in France since 1982 in terms of prevention.

Methods

Using the data on work time schedules collected in the French Labour Force Surveys, sex- and period-specific job-exposure matrices (JEMs) to night work (working between midnight and 5 AM) were developed. After linkage of the JEMs with data of the national censuses of 1982, 1990, 1999, 2007 and 2015, the numbers and proportions of workers usually or occasionally exposed to night work were estimated.

Results

The number of night workers (usual and occasional) increased from 3.67 million in 1982 to 4.37 million in 2015 (15.8% vs 16.4%). Night work was more common in men than in women (e.g. 22.4% vs 10.0% in 2015), and usual night work largely increased after 2000 (4.4% in 1999, 7.2% in 2007). In 2015, 1.29 million men worked usually at night, including 882,000 workers in the service sector (63%) and 360,000 in the manufacturing and extracting industries (28%). For the same period, 581,000 women were usual night workers, most of them being employed in the service sector (90%). Among women, a 97% increase of usual night work was observed between 1982 and 2015.

Conclusions

This study shows that night work involves a growing number of workers in France, particularly in women in the service sector. These results raise concern about the public health impact of night work and particularly about the numbers of outcomes attributable to this exposure such as breast or prostate cancers.
Netizens’ risk perception in new coronary pneumonia public health events: an analysis of spatiotemporal distribution and influencing factors
Authors: Li Yanling , Wu Xiancong , Wang Jihong
Published: July 2022

Background

Internet search volume reflects the level of Internet users’ risk perception during public health events. The Internet search volume index model, an algorithm of concentration of Internet users, and statistical analysis of popular topics on Weibo are used to analyze the effects of time, space, and space-time interaction. We conducted in-depth research on the characteristics of the spatial and temporal distribution of Internet users’ risk perceptions of public health events and the associated influential factors.

Methods

We analyzed the spatiotemporal distribution characteristics of Internet users’ risk perception after the Wuhan “city closing” order during the coronavirus disease 2019 (COVID-19) pandemic. We established five linear regression models according to different time periods and analyzed factors influencing Internet users’ risk perception by employing a Poisson and spatial distribution and topic modeling analysis.

Results

Economy, education, health, and the degree of information disclosure affect Internet users’ risk perception significantly. Internet users’ risk perception conforms to the exponential distribution law in time and has periodic characteristics and stability trends. Additionally, Internet users’ average arrival rate dropped from week 1 to week 8 after the “city closing.” Internet users’ risk perception has a uniform distribution in space, economic and social development level distribution consistency, spatial agglomeration, and other characteristics. The results of the time-space interaction show that after 8 weeks of COVID-19, Internet search hot topics have become more stable, and Internet users’ information demand structure has become more rational.

Conclusions

The Internet search cycle of the COVID-19 event is synchronized with the evolution cycle of the epidemic. The physical risk of Internet users is at the top of the risk structure, focusing on the strong concern about the government’s ability to control COVID-19 and its future trend. The government should strengthen network management; seize the risk control focus of key time nodes, regional locations, and information content of online communication; actively adjust the information content supply; effectively control the rebound of Internet users’ risk perception; establish a data-driven, risk-aware intelligence system for internet users; and guide people to actively face and overcome the potential risks and threats of COVID-19.
Increased shoulder pain across an exercise session and subsequent shoulder exercise: a prospective cohort study
Authors: Trøstrup Jeanette , Svendsen Susanne Wulff , Dalbøge Annett , Mikkelsen Lone Ramer , Høybye Mette Terp , Jørgensen Lene Bastrup , Klebe Thomas Martin , Frost Poul
Published: July 2022

Background

Shoulder complaints are common and the recommended first-line treatment is exercise therapy. However, it remains unknown if increased shoulder pain after an exercise session is a barrier for subsequent exercise dose, particularly in people with high fear-avoidance beliefs. Such knowledge could indicate ways to optimise shoulder rehabilitation. The aim was to examine whether increased shoulder pain across an exercise session was associated with a lower subsequent exercise dose, and if high fear-avoidance beliefs exaggerated this association.

Methods

We conducted a prospective cohort study using data from a randomised controlled trial in Central Denmark Region 2017–2019. Participants were employees (n = 79) with shoulder complaints and high occupational shoulder exposures. The intervention was a home-based or partly supervised exercise programme lasting 2–3 months. Linear mixed models were used to examine the associations between change in shoulder pain and exercise dose (number of repetitions, progression level (1–3), resistance level (1–3), and time until next exercise session [days]).

Results

At baseline, the participants had a median pain intensity at rest of 2 on a numerical rating scale (0–10). For a 1-cm increase in pain on a visual analogue scale (0–10 cm) during an exercise session, the subsequent number of repetitions, progression level and resistance level were − 1.3 (95% confidence interval [CI] − 3.4 to 0.9), 0.0 (95% CI − 0.1 to 0.0) and − 0.0 (95% CI − 0.1 to 0.0), respectively. Likewise, the time until next exercise session was − 0.6 (95% CI − 2.4 to 1.3) days for a 1-cm increase. There were no interactions with fear-avoidance beliefs.

Conclusion

Increased pain across an exercise session was not associated with subsequent exercise dose, regardless of fear-avoidance beliefs, among employees with shoulder complaints and high occupational shoulder exposures.

Trial registration

The trial was registered at Clinicaltrials.gov 19/05/2017 (ID: NCT03159910).
The effect of hydroalcoholic extract of Psidium guajava L. on experimentally induced oral mucosal wound in rat
Authors: Ghaderi Faezeh , Ebrahimi Elham , Sari Aslani Fatemeh , Koohi-Hosseinabadi Omid , Koohpeyma Farhad , Irajie Cambyz , Tanideh Nader , Iraji Aida
Published: July 2022

Background

The aim of this study was to evaluate the biological effects of hydroalcoholic extract of Psidium guajava L leaves and phenytoin as a standard agent on the induced oral mucosal wound.

Methods

Hundred seventy Sprague Dawley rats were grouped in 5 clusters randomly. Oral mucosal wounds were induced in all rats except for the control group. Phenytoin and guajava leaf extract were used as a mouthwash. Twelve rats from the 5 groups were euthanized on day 7th and 10th, and 10 rats from each group were sacrificed on the 14th day. Interleukin-6 and total antioxidant capacity were determined in the serum. The tissues were evaluated for pathological and stereological assessments. Phytochemical analyses were performed on the hydroalcoholic extract of Psidium guajava L to determine the antioxidant potency.

Results

Total phenolic content test and DPPH analysis demonstrated the high potential of antioxidant capacity of Psidium guajava L. Decreasing IL-6 and increasing TAC were seen in the guajava hydroalcoholic extract and phenytoin groups. The difference of IL-6 between the wound treated guajava group and the wounded group was significant. The wound treated guajava group and wound treated phenytoin group on the 14th day increased the number of fibroblast cells and volume density of sub-mucosae effectively to the same thickness to be considered as a healed sub-mucosae layer. The volume density of the epithelium changes showed statistically significant different responses based on gender.

Conclusion

In conclusion, hydroalcoholic extract of Psidium guajava L leaves might exert theraputic effects on oral mucositis.
PTPRO knockdown protects against inflammation in hemorrhage shock-induced lung injury involving the NF-κB signaling pathway
Authors: Huan Zhirong , Tang Ying , Xu Ce , Cai Jimin , Yao Hao , Wang Yan , Bu Fanyu , Ge Xin
Published: July 2022

Background

Hemorrhage shock (HS) is characterized by decreased tissue oxygenation and organ damage due to severe blood loss. Protein tyrosine phosphatase receptor type O (PTPRO) is abnormally up-regulated in the rat lungs after trauma/HS.

Methods

To elucidate the regulatory mechanism of PTPRO in lung inflammation following HS, we established a rat model of HS via withdrawing blood by a catheter inserted into the femoral artery followed by resuscitation. The rats were infected with lentivirus harboring short hairpin RNA (shRNA) targeting PTPRO by intratracheal instillation.

Results

PTPRO was significantly up-regulated in rat lungs after HS. PTPRO knockdown enhanced epithelial integrity and reduced capillary leakage by up-regulating tight junction proteins zonula occludens-1 (ZO-1) and occludin (OCC) in the lungs. Besides, HS-induced myeloperoxidase activity and inflammatory cell infiltration was mitigated by PTPRO knockdown. The expression of inflammatory cytokines/chemokines (TNF-α, IL-6, MIP-2, MCP-1, and KC) in the lungs and bronchoalveolar lavage fluid was regressed after PTPRO knockdown. The nuclear factor kappa B (NF-κB) pathway was involved in HS-induced lung inflammation. PTPRO down-regulation inhibited the NF-κB pathway activation by suppressing the phosphorylation of NF-κB and its translocation from the cytoplasm into the nucleus in HS.

Conclusion

Taken together, we demonstrated that PTPRO knockdown may contribute to attenuating inflammation in HS-induced lung injury via inhibiting NF-κB pathway activation.
The molecular biology and therapeutic potential of Nrf2 in leukemia
Authors: Khodakarami Atefeh , Adibfar Sara , Karpisheh Vahid , Abolhasani Shiva , Jalali Pooya , Mohammadi Hamed , Gholizadeh Navashenaq Jamshid , Hojjat-Farsangi Mohammad , Jadidi-Niaragh Farhad
Published: July 2022

NF-E2-related factor 2 (Nrf2) transcription factor has contradictory roles in cancer, which can act as a tumor suppressor or a proto-oncogene in different cell conditions (depending on the cell type and the conditions of the cell environment). Nrf2 pathway regulates several cellular processes, including signaling, energy metabolism, autophagy, inflammation, redox homeostasis, and antioxidant regulation. As a result, it plays a crucial role in cell survival. Conversely, Nrf2 protects cancerous cells from apoptosis and increases proliferation, angiogenesis, and metastasis. It promotes resistance to chemotherapy and radiotherapy in various solid tumors and hematological malignancies, so we want to elucidate the role of Nrf2 in cancer and the positive point of its targeting. Also, in the past few years, many studies have shown that Nrf2 protects cancer cells, especially leukemic cells, from the effects of chemotherapeutic drugs. The present paper summarizes these studies to scrutinize whether targeting Nrf2 combined with chemotherapy would be a therapeutic approach for leukemia treatment. Also, we discussed how Nrf2 and NF-κB work together to control the cellular redox pathway. The role of these two factors in inflammation (antagonistic) and leukemia (synergistic) is also summarized.
A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML
Authors: Cai Baohuan , Liu Yun , Chong Yating , Mori Stephanie Fay , Matsunaga Atsuko , Zhang Hualei , Fang Xuexiu , Chang Chang-Sheng , Cowell John K. , Hu Tianxiang
Published: July 2022

Background

Myeloid and lymphoid malignancies associated with chimeric FGFR1 kinases are the hallmark of stem cell leukemia and lymphoma syndrome (SCLL). In all cases, FGFR1 kinase is constitutively phosphoactivated as a result of chromosome translocations, which lead to acquisition of dimerization motifs in the chimeric proteins. Recently, we demonstrated that these chimeric kinases could be cleaved by granzyme B to generate a truncated derivative, tnFGFR1, which localized exclusively into the nucleus and was not phosphorylated.

Methods

Stem cell transduction and transplantation in syngeneic mice was used to assess the transforming ability of tnFGFR1 in bone marrow stem cells, and RPPA and RNA-Seq was used to examine the related signaling pathways and regulated target genes.

Results

For the first time, we show that this non-classical truncated form of FGFR1 can independently lead to oncogenic transformation of hematopoietic stem cells in an animal model in vivo. These leukemia cells show a mixed immunophenotype with a B-cell B220 + Igm- profile in the majority of cells and Kit+ in virtually all cells, suggesting a stem cell disease. tnFGFR1, however, does not activate classic FGFR1 downstream signaling pathways but induces a distinct profile of altered gene expression with significant upregulation of transmembrane signaling receptors including FLT3 and KIT. We further show that de novo human AML also express tnFGFR1 which correlates with upregulation of FLT3 and KIT as in mouse leukemia cells. ChIP analysis demonstrates tnFGFR1 occupancy at the Flt3 and Kit promoters, suggesting a direct transcriptional regulation. Cells transformed with tnFGFR1 are insensitive to FGFR1 inhibitors but treatment of these cells with the Quizartinib (AC220) FLT3 inhibitor, suppresses in vitro growth and development of leukemia in vivo. Combined treatment with FGFR1 and FLT3 inhibitors provides increased survival compared to FGFR1 inhibition alone.

Conclusions

This study demonstrates a novel model for transformation of hematopoietic stem cells by chimeric FGFR1 kinases with the combined effects of direct protein activation by the full-length kinases and transcriptional regulation by the truncated nuclear tnFGFR1 derivative, which is associated with GZMB expression levels. Genes significantly upregulated by tnFGFR1 include Flt3 and Kit which promote a leukemia stem cell phenotype. In human AML, tnFGFR1 activation leads to increased FLT3 and KIT expression, and higher FLT3 and GZMB expression levels are associated with an inferior prognosis. These observations provide insights into the relative therapeutic value of targeting FGFR1 and FLT3 in treating AML with this characteristic gene expression profile.
Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions
Authors: Einenkel Rebekka , Ehrhardt Jens , Zygmunt Marek , Muzzio Damián Oscar
Published: July 2022

Early pregnancy is marked by placentation and embryogenesis, which take place under physiological low oxygen concentrations. This oxygen condition is crucial for many aspects of placentation, trophoblast function, vascularization and immune function. Recently, a new family of innate lymphoid cells has been found to be expressed at the fetomaternal interface. Among these, type 3 innate lymphoid cells (ILC3) are important antigen presenting cells in the context of MHC-II. The expression of MHC-II on ILC3s during pregnancy is reduced. We tested the hypothesis that low oxygen concentrations reduce the potential of ILC3s to present antigens promoting fetal tolerance.

Using an in vitro approach, NCR+ILC3s generated from cord blood stem cell precursors were incubated under different O2concentrations in the presence or absence of the pregnancy-related hormones hCG and TGF-β1. The expression of MHC-II, accessory molecules and an activation marker were assessed by flow cytometry. We observed that 1% O2reduced the expression of the MHC-II molecule HLA-DR as compared to 21% O2and modulated the relative effects of hCG and TGF-β1.

Our data indicate that low oxygen concentrations reduce the antigen presentation potential of NCR+ILC3s and suggest that it may promote fetal tolerance during the first trimester of pregnancy.
Dual contraceptives and associated predictors in HIV positive women: a case–control study
Authors: Ashore Alemu , Erkalo Desta , Prakash Ravi
Published: July 2022

Background

People living with the human immune deficiency virus (PLHIV) are an important group to address HIV prevention. Mostly, 90% of the HIV cases in children are usually through mother-to-child transmission. Dual contraception (barrier condoms i.e., male, and female condoms) are one of the most effective ways to avoid HIV transmission. Thus, the present study was carried out to establish the predictors associated with the use of dual contraceptives in sexually active HIV positive women in Hossana, Southern Ethiopia.

Methods

An institution based unmatched case–control study among randomly selected 312 sexually active HIV positive women was conducted from February 2021 to May 2021. The data were collected through structured questionnaire and anti-retroviral treatment (ART) cards considering the case-to-control ratio of 1:3. The information was coded, entered into Epi-Info7.0 and exported to SPSS 20.0 for further analysis. A P-value < 0.25 in bi-variate analysis was further processed for multi-variate analysis and P-value < 0.05 was considered statistically significant.

Results

A response rate of 97.2% was recorded. A significant difference was observed towards the use of dual contraceptives in sexually active HIV positive women living in urban vs rural areas (AOR = 0.28; 95% CI = 0.09–0.84), having sexual intercourse with a regular partner (AOR = 3.77; 95% CI = 1.48–9.55) and taking first initiation to use (AOR = 0.05; 95% CI = 0.02–0.11).

Conclusion

The determinants associated with lower use of dual contraceptives were residing in rural areas, sexual intercourse with a regular partner and low initiation rate at first time for use of dual contraceptives. Therefore, we strongly recommend that open discussion about sexually transmitted infections like HIV and their prevention, providing adequate facilities in rural areas can help to prevent HIV transmission and reduce the disease burden. The health professionals are encouraged to organize awareness campaigns in rural areas for use of dual contraceptives among PLHIV.
Adjunct diagnostic value of radiological findings in mucopolysaccharidosis type IVa-related thoracic spinal abnormalities: a pilot study
Authors: Jan Ya-Ting , Tsai Pei-Shan , Huang Wen-Hui , Huang Shih-Chieh , Liu Yu-Peng , Cheng She-Meng , Huang Kun-Shuo
Published: July 2022

Background

In patients with mucopolysaccharidosis (MPS), systematic assessment and management of cervical instability, cervicomedullary and thoracolumbar junction spinal stenosis and spinal cord compression averts or arrests irreversible neurological damage, improving outcomes. However, few studies have assessed thoracic spinal involvement in MPS IVa patients. We aimed to evaluate thoracic spinal abnormalities in MPS IVa patients and identify associated image manifestations by CT and MRI study.

Results

Data of patients diagnosed and/or treated for MPS IVa at MacKay Memorial Hospital from January 2010 to December 2020 were extracted from medical records and evaluated retrospectively. Computed tomography (CT), plain radiography and magnetic resonance imaging (MRI) findings of MPS IVa-related spinal abnormalities were reviewed. Spine CT and plain radiography findings of 12 patients (6 males and 6 females with median age 7.5 years, range 1–28 years) revealed two subtypes of spinal abnormalities: thoracic kyphosis apex around T2 (subtype 1, n = 8) and thoracic kyphosis apex around T5 (subtype 2, n = 4). Spine CT and plain radiography clearly identified various degrees of thoracic kyphosis with apex around T2 or T5 in MPS IVa patients. Square-shaped to mild central beaking in middle thoracic vertebral bodies was observed in subtype 1 patients, while greater degrees of central beaking in middle thoracic vertebral bodies was observed in subtype 2 patients.

Conclusions

Spine CT findings clearly identify new radiological findings of thoracic kyphosis apex around T2 or T5 in MPS IVa patients. The degrees of central beaking at middle thoracic vertebral bodies may be a critical factor associated with different image presentations of thoracic kyphosis.
Salmonella serovars in sheep and goats and their probable zoonotic potential to humans in Suez Canal Area, Egypt
Authors: Hawwas Hanan Abd El-Halim , Aboueisha Abdel-Karim Mahmoud , Fadel Hanaa Mohamed , El-Mahallawy Heba Sayed
Published: July 2022

Background

Salmonella is one of the most common and economically important zoonotic pathogens. This study aimed to determine the occurrence of Salmonella serovars in sheep and goats and their probable zoonotic risk to humans in Suez Canal area in Egypt. A total of 320 fecal samples from sheep (n = 120), goats (n = 100), and humans (n = 100) were collected and examined for the presence of Salmonella based on cultural and biochemical characteristics, and serological analysis. Moreover, the virulence of the identified Salmonella isolates was assessed by molecular screening for invA, stn, spvC, and sopB virulence genes using PCR.

Results

Overall, the occurrence of Salmonella in sheep feces (23.3%) was higher than that in goat feces (7%) and human stool (13%) in the study area. The identified isolates belonged to 12 serotypes; ten, five, and eight from sheep, goats, and humans, respectively. The most frequently identified serotypes were S. Typhimurium from sheep feces, and S. Enteritidis from both goat feces and human stool, with four serotypes; S. Typhimurium, S. Enteritidis, S. Dublin and S. Saintpaul, were mutually shared between all of them. Demographic data revealed that diarrheic sheep (85.7%) and goats (25%) had a higher risk for Salmonella fecal carriage than non-diarrheic ones (19.5% and 6.25%, respectively). The prevalence of Salmonella infection in humans in contact with sheep and goats (28%) was significantly higher than its prevalence in people having a history of contact with animals other than sheep and goats (10%) and those having no history of animal contact (7.3%) (χ2 = 6.728, P ˂ 0.05). The stn, spvC, and sopB genes were detected in 98.1% of the isolates, with a significant, very strong positive correlation for their mutual presence (P < 0.05). Approximately 40.7% of isolates that carried the invA gene had a non-significant, very weak positive correlation with other virulence genes. The most common genotypic virulence profile for all isolates was stn, spvC, and sopB; however, invA, stn, spvC, and sopB was the frequent virulotype for S. Typhimurium, S. Tsevie, S. Apeyeme, and S. Infantis.

Conclusions

The present study highlights the role of apparently healthy and diarrheic sheep and goats as reservoirs and sources of human infection with virulent Salmonella serovars in the Suez Canal area.
Depression and suicidal behavior among adolescents living with HIV in Botswana: a cross-sectional study
Authors: Olashore Anthony A. , Paruk Saeeda , Tshume Ontibile , Chiliza Bonginkosi
Published: July 2022

Background

Depression and suicidal behavior are the main causes of disability and morbidity, especially in adolescents living with HIV (ALWHIV). Data regarding these are lacking in Botswana, a country with a predominantly youthful population and ranked among the top four in the world most affected by HIV. Therefore, the present study aimed to estimate the prevalence of depression and suicidal behavior and explore their associated factors in Botswana ALWHIV.

Methods

Responses were obtained from 622 ALWHIV using the DSM-5 and the Mini-International Neuropsychiatric Interview for Children and Adolescents.

Results

The mean age (SD) of the participants was 17.7 (1.60) years and more males (54.3%) participated than females. Depression and suicidal behavior rates among adolescents were 23% and 18.9%, respectively. Female participants were more likely to be depressed (AOR = 1.96; 95% CI 1.11–3.45) and have suicidal behaviour (AOR = 6.60; 95% CI 3.19–13.7). Loss of mother (AOR = 2.87; 95% CI 1.08–7.62) and viral load of 400 copies and above (AOR = 5.01; 95% CI 2.86–8.78) were associated with depression. Alcohol use disorder (AOR = 3.82; 95% CI 1.83–7.96) and negative feelings about status (AOR = 8.79; 95% CI 4.62–16.7) were associated with suicidal behavior. Good support (AOR = 0.42; 95% CI 0.23–0.76) and increased frequency of religious activities were protective (AOR = 0.33; 95% CI 0.14–0.79) against depression and suicidal behaviour, respectively.

Conclusion

Therefore, routine psychologic screening, which includes identifying psychological stressors and maladaptive coping, family and caregiver support services, and psychosocial support platforms, should be integrated into the management package for ALWHIV in Botswana.
Congenital hypothyroidism after newborn screening program reorganization in the Apulia region
Authors: Simonetti Simonetta , D’Amato Gabriele , Esposito Benedetta , Chiarito Mariangela , Dentico Domenico , Lorè Tania , Cardinali Roberta , Russo Silvia , Laforgia Nicola , Faienza Maria Felicia
Published: July 2022

Background

Congenital hypothyroidism (CH) is the most frequent congenital endocrine disorder. The purpose of the present study was to evaluate the incidence and etiological classification of CH in Apulia in a three-year period according to the reorganization of the regional screening program in a single central laboratory, as well as to analyze the growth characteristics and the associated risk factors of the CH newborns diagnosed during the study period.

Methods

Data derived from the reorganization of the newborn screening program for CH in a single central laboratory that collects dried blood spot (DBS) from 27 Maternity Hospitals are analyzed over a three-year period. Birth weight and length, daily dose of L-T4 at specific key points (3, 6, 12 and 18 months, 2, 2.5 and 3 years) were also obtained from medical records of the CH newborns during the study period and calculated as standard deviation score (SDS).

Results

The screening program diagnosed 90 newborns with confirmed CH (incidence 1:990; recall rate: 3.6%). In detail, 75.6% newborns had an eutopic thyroid, and 24.4% had thyroid dysgenesis; 33 out of the 90 newborns (36.6%) had one or more risk factors. Among these, the multiple pregnancies are the most important because they tripled the risk of CH. At diagnosis, TSH levels were different between patients with dysgenesis and those with an eutopic thyroid (p = 0.005). Treatment was started at a mean of 18.5 ± 12.8 days of life. The mean starting dose of levothyroxine (L-T4) was 11.38 ± 2.46 μg/kg/day.

Conclusions

The results of these study show an increase of CH cases in newborns with an eutopic thyroid compared to the traditional classification. The centralization of the screening program allows a closer cooperation between laboratory and clinical centers and facilitates the implementation of appropriate diagnostic evaluations and timely initiation of treatment, with positive effects on the management of the condition.
Distal Arthrogryposis type 5 in an Italian family due to an autosomal dominant gain-of-function mutation of the PIEZO2 gene
Authors: Serra Gregorio , Antona Vincenzo , Cannata Chiara , Giuffrè Mario , Piro Ettore , Schierz Ingrid Anne Mandy , Corsello Giovanni
Published: July 2022

Background

Arthrogryposis multiplex congenita (AMC) is a group of clinically and etiologically heterogeneous conditions, characterized by prenatal onset contractures affecting two or more joints. Its incidence is about 1 in 3000 live births. AMC may be distinguished into amyoplasia, distal and syndromic arthrogryposis. Distal arthrogryposis (DA) predominantly affects hands and feet. It is currently divided into more than ten subtypes (DA1, DA2A/B, DA3–10), based on clinical manifestations, gene mutations and inheritance pattern. Among them, only a few patients with DA5 have been reported. It is associated to a gain-of-function pathogenic variant of thePIEZO2gene, encoding for an ion-channel necessary to convert mechanical stimulus to biological signals and crucial for the development of joints, neuromuscular and respiratory systems. Main clinical features include multiple distal contractures, short stature, ptosis, ophthalmoplegia and, in some cases, restrictive lung disease.

Case presentation

Hereby, we report on a four-generation Italian family with DA5. Our first proband was a newborn with prenatal suspicion of AMC. At birth, clinical findings were compatible with a DA diagnosis. Family history was positive for the mother withshort stature,ophthalmoplegia, short neck, and contractures of the joints of distal extremities, and for three other relatives on the maternal side, including grandfather and great-grandmother, who all shared similar findings. Thus, we performed a next generation sequencing analysis (NGS) of the genes associated to AMC and of those involved in DA. The gain-of-function heterozygous mutation c.8181_8183delAGA (p.Glu2727del) ofPIEZO2was identified in the proband, and the same mutation was also found in the mother, confirming the autosomal dominant inheritance of the condition.

Conclusions

Our patients contribute to the current DA5 genomic database, and to a better characterization of the disease. Clinicians may have suspicion of a DA diagnosis based on suggestive (also prenatal) clinical findings, which must be then confirmed by NGS analysis. Since natural history varies widely among different DA disorders, detection of the underlying causal variant is essential for the identification of the exact subtype, and to its adequate management, which must rely on a multidisciplinary and individualized approach.
Novel de novo missense mutation in the interferon regulatory factor 6 gene in an Italian infant with IRF6-related disorder
Authors: Schierz Ingrid Anne Mandy , Amoroso Salvatore , Antona Vincenzo , Giuffrè Mario , Piro Ettore , Serra Gregorio , Corsello Giovanni
Published: July 2022

Background

Congenital maxillomandibular syngnathia is a rare craniofacial anomaly leading to difficulties in feeding, breathing and ability to thrive. The fusion may consist of soft tissue union (synechiae) to hard tissue union. Isolated cases of maxillomandibular fusion are extremely rare, it is most often syndromic in etiology.

Case presentation

Clinical management of a female newborn with oromaxillofacial abnormities (synechiae, cleft palate, craniofacial dysmorphisms, dental anomaly) and extraoral malformations (skinfold overlying the nails of both halluces, syndactyly, abnormal external genitalia) is presented. The associated malformations addressed to molecular genetic investigations revealing an interferon regulatory factor 6 (IRF6)-related disorder (van der Woude syndrome/popliteal pterygium syndrome). A novel de novo heterozygous mutation in exon 4 of IRF6 gene on chromosome 1q32.2, precisely c.262A > G (p.Asn88Asp), was found. Similarities are discussed with known asparagine missense mutations in the same codon, which may alter IRF6 gene function by reduced DNA-binding ability. A concomitant maternal Xp11.22 duplication involving two microRNA genes could contribute to possible epigenetic effects.

Conclusions

Our reported case carrying a novel mutation can contribute to expand understandings of molecular mechanisms underlying synechiae and orofacial clefting and to correct diagnosing of incomplete or overlapping features in IRF6-related disorders. Additional multidisciplinary evaluations to establish the phenotypical extent of the IRF6-related disorder and to address family counseling should not only be focused on the surgical corrections of syngnathia and cleft palate, but also involve comprehensive otolaryngologic, audiologic, logopedic, dental, orthopedic, urological and psychological evaluations.
A longitudinal assessment of trial protocols approved by research ethics committees: The Adherance to SPIrit REcommendations in the UK (ASPIRE-UK) study
Authors: Speich Benjamin , Odutayo Ayodele , Peckham Nicholas , Ooms Alexander , Stokes Jamie R. , Saccilotto Ramon , Gryaznov Dmitry , von Niederhäusern Belinda , Copsey Bethan , Altman Douglas G. , Briel Matthias , Hopewell Sally
Published: July 2022

Background

To assess the quality of reporting of RCT protocols approved by UK research ethics committees before and after the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline.

Methods

We had access to RCT study protocols that received ethical approval in the UK in 2012 (n=103) and 2016 (n=108). From those, we assessed the adherence to the 33 SPIRIT items (i.e. a total of 64 components of the 33 SPIRIT items). We descriptively analysed the adherence to SPIRIT guidelines as proportion of adequately reported items (median and interquartile range [IQR]) and stratified the results by year of approval and sponsor.

Results

The proportion of reported SPIRIT items increased from a median of 64.9% (IQR, 57.6–69.2%) in 2012 to a median of 72.5% (IQR, 65.3–78.3%) in 2016. Industry-sponsored RCTs reported more SPIRIT items in 2012 (median 67.4%; IQR, 64.1–69.4%) compared to non-industry-sponsored trials (median 59.8%; IQR, 46.5–67.7%). This gap between industry- and non-industry-sponsored trials increased in 2016 (industry-sponsored: median 75.6%; IQR, 71.2–79.0% vs non-industry-sponsored: median 65.3%; IQR, 51.6–76.3%).

Conclusions

The adherence to SPIRIT guidelines has improved in the UK from 2012 to 2016 but remains on a modest level, especially for non-industry-sponsored RCTs.
Impact of probiotic supplementation on exercise endurance among non-elite athletes: study protocol for a randomized, placebo-controlled, double-blind, clinical trial
Authors: McDermott Caitlin E. , Vincent Heather K. , Mathews Anne E. , Cautela Brunella Gonzalez , Sandoval Mariana , Tremblay Annie , Langkamp-Henken Bobbi
Published: July 2022

Background

Some probiotics appear to improve athletic performance, endurance, and recovery after intense exercise. Other formulations may provide performance-related benefits via immune and gastrointestinal functions in athletic individuals. However, few formulations have been studied for both types of effects among non-elite athletes. The primary objective of this study is to assess the ergogenic effects of a probiotic on high-intensity endurance running performance in non-elite runners. Secondary objectives include assessment of perceived exertion, blood chemistry, immune and stress biomarkers, cold and flu symptoms, and gastrointestinal health after the probiotic intervention.

Methods

This 9-week randomized, placebo-controlled, double-blind, parallel trial will assess the ergogenic effects of a probiotic (5 billion colony-forming units/day, for 6 weeks) in healthy, non-elite runners (N=32; 18–45 years). Participants will be monitored via daily and weekly questionnaires during the 2-week pre-baseline, 6-week intervention, and 1-week washout. Questionnaires will inquire about activity, muscle soreness, gastrointestinal symptoms, cold and flu symptoms, stool form and frequency, and adverse events. During the pre-baseline visit, maximal oxygen uptake (V̇O2max) is assessed to set appropriate individualized workload settings for the treadmill time-to-exhaustion endurance tests. These time-to-exhaustion endurance running tests will be completed at an intensity of 85% VO2max at baseline and final visits. During these tests, self-perceived exercise effort will be rated via the Borg Rating of Perceived Exertion scale and finger sticks assessing capillary blood glucose and lactate concentrations will be collected every 3 min. Additional questionnaires will assess diet and motivation to exercise. Body composition will be assessed using air displacement plethysmography at the baseline and final visits. Hypotheses will be tested using two-sided tests, and a linear model and with a type I error rate ofα=0.05. Primary and secondary outcomes will be tested by comparing results between the intervention groups, adjusting for baseline values.

Discussion

These results will build evidence documenting the role of probiotics on running endurance performance and physiological responses to exercise in non-elite athletes. Understanding the potential mechanisms of probiotic effects and how they mitigate the intestinal or immune discomforts caused by running could provide additional strategy means to help runners improve their performance.

Trial registration number

ClinicalTrials.govNCT04588142. Posted on October 19, 2020.

Protocol version: July 2, 2021, version 1.2
A fat body transcriptome analysis of the immune responses of Rhodnius prolixus to artificial infections with bacteria
Authors: Salcedo-Porras Nicolas , Oliveira Pedro Lagerblad , Guarneri Alessandra Aparecida , Lowenberger Carl
Published: July 2022

Background

Rhodnius prolixus is an important vector of Trypanosoma cruzi, the causal agent of Chagas disease in humans. Despite the medical importance of this and other triatomine vectors, the study of their immune responses has been limited to a few molecular pathways and processes. Insect immunity studies were first described for holometabolous insects such as Drosophila melanogaster, and it was assumed that their immune responses were conserved in all insects. However, study of the immune responses of triatomines and other hemimetabolous insects has revealed discrepancies between these and the Drosophila model.

Methods

To expand our understanding of innate immune responses of triatomines to pathogens, we injected fifth instar nymphs of R. prolixus with the Gram-negative (Gr−) bacterium Enterobacter cloacae, the Gram-positive (Gr+) bacterium Staphylococcus aureus, or phosphate-buffered saline (PBS), and evaluated transcript expression in the fat body 8 and 24 h post-injection (hpi). We analyzed the differential expression of transcripts at each time point, and across time, for each treatment.

Results

At 8 hpi, the Gr− bacteria-injected group had a large number of differentially expressed (DE) transcripts, and most of the changes in transcript expression were maintained at 24 hpi. In the Gr+ bacteria treatment, few DE transcripts were detected at 8 hpi, but a large number of transcripts were DE at 24 hpi. Unexpectedly, the PBS control also had a large number of DE transcripts at 24 hpi. Very few DE transcripts were common to the different treatments and time points, indicating a high specificity of the immune responses of R. prolixus to different pathogens. Antimicrobial peptides known to be induced by the immune deficiency pathway were induced upon Gr− bacterial infection. Many transcripts of genes from the Toll pathway that are thought to participate in responses to Gr+ bacteria and fungi were induced by both bacteria and PBS treatment. Pathogen recognition receptors and serine protease cascade transcripts were also overexpressed after Gr− bacteria and PBS injections. Gr- injection also upregulated transcripts involved in the metabolism of tyrosine, a major substrate involved in the melanotic encapsulation response to pathogens.

Conclusions

These results reveal time-dependent pathogen-specific regulation of immune responses in triatomines, and hint at strong interactions between the immune deficiency and Toll pathways.

Graphical abstract
Association between serum lipid profile and liver fibrosis in patients infected with Schistosoma japonicum
Authors: Liu Yang , Zhang PengPeng , Li JunHui , Li Hao , Zhou Chen , Zhang Yu , Ming YingZi
Published: July 2022

Background

Liver fibrosis is thought to have a close relationship with lipid profile. The possible association between lipids and liver fibrosis of different etiologies has been widely explored. However, the association between lipids and liver fibrosis in patients infected with Schistosoma japonicum remains unclear. In the present study we undertook a preliminary exploration of the association between lipid profile and liver fibrosis, and developed a new predictive index for liver fibrosis in S. japonicum-infected patients.

Methods

A total of 1503 patients diagnosed with S. japonicum at Xiangyue Hospital, China were enrolled in this retrospective study. The patients were divided into two groups, i.e., those with and those without liver fibrosis, by two experienced schistosomiasis specialists, according to the results of liver ultrasound examination. Demographic, clinical, and laboratory data were collected. Multivariable logistic models were used to estimate the independent associations between lipid profile and liver fibrosis. Receiver operating characteristic (ROC) curves were used to assess the discriminative ability of the new index in predicting liver fibrosis in patients with schistosomiasis.

Results

Logistic regression analysis showed that high-density lipoprotein (HDL) [adjusted odds ratio (aOR), 95% confidence interval (CI) 7.334, 5.051–10.649; P < 0.001], low-density lipoprotein (LDL) (aOR, 95% CI 0.434, 0.370–0.509; P < 0.001), hemoglobin (HB) (aOR, 95% CI 0.979, 0.971–0.987; P < 0.001) and platelets (PLT) (aOR, 95% CI 0.996, 0.994–0.999; P < 0.001) were independently associated with liver fibrosis in patients with schistosomiasis. ROC analysis indicated that the combination of HDL, LDL and HB levels [(HDL × 100)/(LDL × HB)] had a higher area under the ROC curve (AUC = 0.773), and thus may better predict liver fibrosis than the aspartate transaminase-to-platelet ratio index (AUC = 0.608) and fibrosis index based on four factors (AUC = 0.624).

Conclusions

To the best of our knowledge, this is the first study to report that HDL, LDL, HB and PLT levels are independently associated with liver fibrosis in patients with schistosomiasis. (HDL × 100)/(LDL × HB) outperformed the aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors in terms of ROC, and thus could be a new predictive index for liver fibrosis. These findings may help clinicians to more easily and effectively diagnose liver fibrosis in patients with schistosomiasis.

Graphical abstract