bluuebunny/crossref_metadata_2025 huggingface dataset:
Dealing with low access to harm reduction: a qualitative study of the strategies and risk environments of people who use drugs in a small Swedish city
Authors: Holeksa Julie
Published: March 2022

Background

The development of harm reduction has been limited in many areas of Sweden. This study aims to understand the implications that this has for the life circumstances and risk management of people who use drugs in areas of low access.

Methods

Eleven qualitative, semi-structured interviews were undertaken with people who use drugs in a small urban centre with no needle and syringe exchange program (NSP) or Housing First policy.

Results

Participants reported many solutions to lack of NSP, including travel to an external NSP, creating bridging distribution networks, stealing, borrowing, reusing, ordering online, and smuggling injection equipment. They were at risk of having their equipment confiscated by police. Participants were mostly homeless, and to address exclusion from housing services, were forced to frequently find new temporary solutions, sheltering themselves in public places, with friends, in cars, among others. Participants felt the lack of services reflected stigmatized notions of drug use and heightened their exclusion from general society. For example, they avoided accessing other health care services for fear of discrimination. These issues caused high levels of stress and anxiety, in addition to serious risk for many somatic and psychological health conditions, including HIV and HCV transmission.

Conclusion

Lack of harm reduction services placed a great burden on study participants to develop strategies due to gaps in official programming. It also contributes to a vicious cycle of exclusion from services. The implementation of such evidence-based programs will reduce this burden, as well as provide the indirect, symbolic effect of inclusion.
One-month alcohol abstinence national campaigns: a scoping review of the harm reduction benefits
Authors: de Ternay Julia , Leblanc Pierre , Michel Philippe , Benyamina Amine , Naassila Mickael , Rolland Benjamin
Published: March 2022

Over the last decade, one-month alcohol abstinence campaigns (OMACs) have been implemented within the general population in an increasing number of countries. We identified the published studies reporting data on OMACs to explore the following aspects: profile of participants, rates and factors associated with the completion of the abstinence challenge, and outcomes and harm reduction benefits in participating in the challenges. We screened 322 records, including those found in the grey literature, and reviewed 6 studies and 7 Dry July Annual Reports. Compared to non-participating alcohol users, participants were more likely to be female, have a higher income, and a higher level of education. They were heavier drinkers and were more concerned by the consequences of alcohol on health and by their health in general. Participants who achieved the one-month abstinence challenge were lower drinkers and more likely to have registered on the campaign-related Internet communities. Both successful and unsuccessful participants frequently reported health benefits, including sleep improvement and weight loss. Successful participants were more likely to durably change their alcohol drinking habits. Overall, OMACs provide short- or mid-term harm reduction benefits for both successful and unsuccessful participants. Findings were limited by the paucity of studies, their observational nature, and heterogeneity in the features of the different national campaigns, which would probably gain in enhanced internationalization.
Cross-cultural adaptation of the Spanish MINICHAL instrument into English for use in the United Kingdom
Authors: Jordan Andrew N. , Anning Christine , Wilkes Lindsay , Ball Claire , Pamphilon Nicola , Clark Christopher E. , Bellenger Nicholas G. , Shore Angela C. , Sharp Andrew S. P. , Valderas Jose M.
Published: March 2022

Background

Hypertension is a highly prevalent condition, with optimal treatment to BP targets conferring significant gains in terms of cardiovascular outcomes. Understanding why some patients do not achieve BP targets would be enhanced through greater understanding of their health-related quality of life (HRQoL). However, the only English language disease-specific instruments for measurement of HRQoL in hypertension have not been validated in accordance with accepted standards. It is proposed that the Spanish MINICHAL instrument for the assessment of HRQoL in hypertension could be translated, adapted and validated for use in the United Kingdom. The aim of the study was therefore to complete this process.

Methods

The MINICHAL authors were contacted and the original instrument obtained. This was then translated into English by two independent English-speakers, with these versions then reconciled, before back-translation and subsequent production of a 2nd reconciled version. Thereafter, a final version was produced after cognitive debriefing, for administration and psychometric analysis in the target population of patients living in the Exeter area (Southwest UK) aged 18–80 years with treatment-naïve grade II-III hypertension, before, during and after 18 weeks’ intensive treatment.

Results

The English-language instrument was administered to 30 individuals (median age: 58.5 years, 53% male). Psychometric analysis demonstrated a floor effect, though no ceiling effect. Internal consistency for both state of mind (StM) and somatic manifestations (SM) dimensions of the instrument were acceptable (Cronbach’s alpha = 0.81 and 0.75), as was test–retest reliability (ICC = 0.717 and 0.961) and construct validity, which was measured through co-administration with the EQ-5D-5L and Bulpitt-Fletcher instruments. No significant associations were found between scores and patient characteristics known to affect HRQoL. The EQ-5D-5L instrument found an improvement in HRQoL following treatment, with the StM and SM dimensions of the English language MINICHAL trending to support this (d = 0.32 and 0.02 respectively).

Conclusions

The present study details the successful English translation and validation of the MINICHAL instrument for use in individuals with hypertension. The data reported also supports an improvement in HRQoL with rapid treatment of grade II-III hypertension, a strategy which has been recommended by contemporaneous European guidelines.

Trial registration ISRCTN registry number: 57475376 (assigned 25/06/2015).
Comparison of prolonged postoperative ileus between laparoscopic right and left colectomy under enhanced recovery after surgery: a propensity score matching analysis
Authors: Lin Zhenmeng , Yang Chunkang , Wang Yi , Yan Mingfang , Zheng Huizhe
Published: March 2022

Background

There were differences in the recovery of bowel function and prolonged postoperative ileus (PPOI) between laparoscopic right colectomy (RC) and left colectomy (LC) under the guidance of enhanced recovery after surgery.

Methods

We selected 870 patients who underwent elective laparoscopic colectomy from June 2016 to December 2021, including 272 patients who had RC and 598 who had LC. According to 1:1 proportion for propensity score matching and correlation analysis, 247 patients who had RC and 247 who had LC were finally enrolled.

Results

The incidence of PPOI in all patients was 13.1%. Age, sex, smoking habit, preoperative serum albumin level, operation type, and operation time were the important independent risk factors based on multivariate logistic regression and correlation analysis for PPOI (p<0.05). Age, sex, body mass index, preoperative serum albumin level, operation time, and degree of differentiation between the two groups were significantly different before case matching (p<0.05). There were no statistically significant differences in baseline characteristics and preoperative biochemical parameters between the two groups after case matching (p>0.05). The incidence of PPOI in patients who had RC was 21.9%, while that in patients who had LC was 13.0%. The first flatus, first semi-liquid, and length of stay in LC patients were lower than those in RC patients (p<0.05).

Conclusion

The return of bowel function in LC was faster than that in RC, and the incidence of PPOI was relatively lower. Therefore, caution should be taken during the early feeding of patients who had laparoscopic RC.
Effect of deploying biomedical equipment technician on the functionality of medical equipment in the government hospitals of rural Nepal
Authors: Thapa Rita , Yih Alison , Chauhan Ashish , Poudel Salomi , Singh Sagar , Shrestha Suresh , Tamang Suresh , Shrestha Rishav , Rajbhandari Ruma
Published: March 2022

Background

Medical equipment plays a crucial role in the provision of quality healthcare services, despite this more than 50% of equipment in developing countries are non-functioning due to a lack of appropriate human resources to maintain. To address this problem some government hospitals of Nepal have deployed a mid-level technical cadre called 'Biomedical Equipment Technician' (BMET). This study aims to evaluate the effectiveness of deploying a BMET on the functionality of medical equipment in government hospitals of rural Nepal.

Methods

We used a mixed-methods approach with a comparative research design. A comprehensive range of 2189 pieces of medical equipment at 22 hospitals with and without BMET were observed to assess their functional status. Medical equipment were stratified into 6 categories based on department and T tests were conducted. We collected qualitative data from 9 BMETs, 22 medical superintendents, and 22 health staff using semi-structured interviews and focus-group discussions. Thematic content analysis was conducted to explore how the BMET's work was perceived.

Findings

The quantity of non-functional devices in hospitals without BMETs was double that of hospitals with BMETs (14% and 7% respectively, p < 0.005). Results were similar across all departments including General (16% versus 3%, p = 0.056), Lab (15% versus 7%, p < 0.005) and Operation Theater (14% versus 5%, p < 0.005). Hospitals with BMETs had fewer overall non-functional devices requiring simple or advanced repair compared to hospitals without BMETs [3% versus 7% (p < 0.005) simple; 4% versus 6% (p < 0.005) advanced]. In our qualitative analysis, we found that BMETs were highly appreciated by hospital staff. Hospital workers perceived that having a BMET on staff, rather than twice-yearly visits from central-level maintenance technicians, is an effective way to keep medical equipment functional. However, without a favorable working environment, the BMET alone cannot perform optimally.

Conclusions

Having a BMET at a rural government hospital has a substantial positive effect on the functional status of medical devices at the hospital. BMETs should be deployed at all rural hospitals to increase the functionality of medical devices, thereby improving the working environment and quality of health services provided.
Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy
Authors: Mashiko Takanobu , Tsukada Kunihisa , Takada Hitomi , Wu Szu-Hsien , Kanayama Koji , Asahi Rintaro , Mori Masanori , Kurisaki Akira , Oka Shinichi , Yoshimura Kotaro
Published: March 2022

Background

The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients.

Methods

All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV− healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry.

Results

The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV.

Conclusions

Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes’ sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.
The patterns of co-occurrence variation are explained by the low dependence of bark beetles (Coleoptera: Scolytinae and Platypodinae) on hosts along altitude gradients
Authors: Luo Fang , Meng Ling-Zeng , Wang Jian , Liu Yan-Hong
Published: March 2022

Background

Separation of biotic and abiotic impacts on species diversity distribution patterns across a significant climatic gradient is a challenge in the study of diversity maintenance mechanisms. The basic task is to reconcile scale-dependent effects of abiotic and biotic processes on species distribution models. Here, we used a hierarchical modeling method to detect the host specificities of bark beetles (Scolytinae and Platypodinae) with their dependent tree communities across a steep climatic gradient, which was embedded within a relatively homogenous spatial niche.

Results

Species turnover of both trees and bark beetles have an opposite pattern along the climatic proxy (represented by the elevation gradients) at the regional scale, but not at local spatial scales. This pattern confirmed the hypothesis wherein emphasis was on influences of macro-climate on local biotic interactions between trees and hosted bark beetle communities, whereas local biotic relations, represented by host specificity dependence, were regionally conserved.

Conclusions

At a confined spatial scale, cross-taxa comparisons of β-diversity highlighted the importance of simultaneous impacts from both extrinsic factors related to geography and environment, and intrinsic factors related to organism characteristics. The effects of tree abundance and phylogeny diversity on bark beetle diversity were, to a large extent, indirect, operating via changes in bark beetle abundance through spatial and temporal dynamics of resources distribution. Tree host dependence, which was considered and represented by host specificities, plays a minor role on the hosted beetle community in this concealed wood decomposing interacting system.
Application of a VP4/VP2-inferred transmission clusters in estimating the impact of interventions on rhinovirus transmission
Authors: Ng Kim Tien , Ng Liang Jie , Oong Xiang Yong , Chook Jack Bee , Chan Kok Gan , Takebe Yutaka , Kamarulzaman Adeeba , Tee Kok Keng
Published: March 2022

Background

Despite the clinical burden attributable to rhinovirus (RV) infections, the RV transmission dynamics and the impact of interventions on viral transmission remain elusive.

Methods

A total of 3,935 nasopharyngeal specimens were examined, from which the VP4/VP2 gene was sequenced and genotyped. RV transmission clusters were reconstructed using the genetic threshold of 0.005 substitutions/site, estimated from the global VP4/VP2 sequences. A transmission cluster is characterized by the presence of at least two individuals (represent by nodes), whose viral sequences are genetically linked (represent by undirected edges) at the estimated genetic distance threshold supported by bootstrap value of ≥ 90%. To assess the impact of facemask, pleconaril and social distancing on RV transmission clusters, trials were simulated for interventions with varying efficacy and were evaluated based on the reduction in the number of infected patients (nodes) and the reduction in the number of nodes-connecting edges. The putative impact of intervention strategies on RV transmission clusters was evaluated through 10,000 simulations.

Results

A substantial clustering of 168 RV transmission clusters of varying sizes were observed. This suggests that RV disease burden observed in the population was largely due to multiple sub-epidemics, predominantly driven by RV-A, followed by RV-C and -B. No misclassification of RV species and types were observed, suggesting the specificity and sensitivity of the analysis. Through 10,000 simulations, it was shown that social distancing may be effective in decelerating RV transmission, by removing more than 95% of nodes and edges within the RV transmission clusters. However, facemask removed less than 8% and 66% of nodes and edges, respectively, conferring moderate advantage in limiting RV transmission.

Conclusion

Here, we presented a network-based approach of which the degree of RV spread that fuel disease transmission in the region was mapped for the first time. The utilization of RV transmission clusters in assessing the putative impact of interventions on disease transmission at the population level was demonstrated.
Maternal and health care workers’ perspectives on exclusive breastfeeding in the context of maternal HIV infection, in Busia county, western Kenya: a mixed methods cross-sectional survey
Authors: Nabakwe Esther Clyde , Egesah Omar , Kiverenge-Ettyang Grace Adisa
Published: March 2022

Background

World Health Organization recommends exclusive breastfeeding (EBF) for 6 months with maternal active antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT) of HIV. However, EBF in low resource settings remains low. We explored perspectives of EBF by HIV-infected mothers and health care workers in Busia County with a high prevalence of HIV to understand factors influencing the practice.

Methods

A mixed methods cross-sectional survey using concurrent quantitative and qualitative data collection methods was conducted at PMTCT clinics. Data on socio-demography, young infant feeding practices, maternal and infant health was collected between February 2013 and August 2015 from 371 purposively sampled HIV-infected mother-infant dyads using a semi-structured questionnaire. Focus group discussions with mothers, in-depth interviews and passive observation of health care workers during interaction with mothers were conducted. Significance of difference between mothers practicing EBF or not was tested by Chi-square and Fisher’s exact tests setting significance level at 5%. Qualitative data was coded and content analyzed to generate themes.

Results

Three hundred and forty-nine (94%) mothers practiced EBF. Maternal comprehension of EBF to PMTCT of HIV influenced choice and practice of EBF (P value = 0.019 and < 0.001 respectively). Health care workers emphasized adherence to ART and offered nutritional supplementation during EBF. Health care workers’ nutritional counseling in the context of maternal HIV was poor. Mentor mothers shared their experiences with mothers and offered live case demonstrations of their successfully EBF, healthy and HIV-uninfected children. The main threats to EBF were teenage motherhood, low maternal education and working during EBF.

Conclusions

EBF among HIV-infected mothers in Busia County, Kenya was high. Health education and counselling by health care workers, maternal comprehension of ART adherence to PMTCT of HIV, nutritional supplementation and mentor mothers’ peer counseling using live case demonstrations of HIV-uninfected EBF children promoted and sustained practice of EBF for 6 months. Teenage motherhood, low maternal education and having to work threatened EBF,
WSES guidelines on blunt and penetrating bowel injury: diagnosis, investigations, and treatment
Authors: Smyth Luke , Bendinelli Cino , Lee Nicholas , Reeds Matthew G. , Loh Eu Jhin , Amico Francesco , Balogh Zsolt J. , Di Saverio Salomone , Weber Dieter , ten Broek Richard Peter , Abu-Zidan Fikri M. , Campanelli Giampiero , Beka Solomon Gurmu , Chiarugi Massimo , Shelat Vishal G. , Tan Edward , Moore Ernest , Bonavina Luigi , Latifi Rifat , Hecker Andreas , Khan Jim , Coimbra Raul , Tebala Giovanni D. , Søreide Kjetil , Wani Imtiaz , Inaba Kenji , Kirkpatrick Andrew W. , Koike Kaoru , Sganga Gabriele , Biffl Walter L. , Chiara Osvaldo , Scalea Thomas M. , Fraga Gustavo P. , Peitzman Andrew B. , Catena Fausto
Published: March 2022

The aim of this paper was to review the recent literature to create recommendations for the day-to-day diagnosis and surgical management of small bowel and colon injuries. Where knowledge gaps were identified, expert consensus was pursued during the 8th International Congress of the World Society of Emergency Surgery Annual (September 2021, Edinburgh). This process also aimed to guide future research.
Three-dimensional digital anatomical measurement of modified sacroiliac screws
Authors: Wang Tingguang , Zhao Bei , Yan Jun , Wang Jia , Chen Chong , Mu Weidong
Published: March 2022

Purpose

To rebuild a model of the pelvis and effectively simulate the trajectory of modified sacroiliac screws, we measured the parameters of each screw and screw channel and assessed the safety and feasibility of the parameters in adults.

Method and materials

One hundred (50 males and 50 females) normal adult pelvic computed tomography (CT) images were randomly selected and imported into Mimics software to rebuild the three-dimensional pelvis model. In these models, each ideal channel of modified screws was simulated, and then we obtained the precise parameters of screws and channels using Mimics and Three-matic software.

Results

The results of the comparison (right vs. left) showed that there were no significant differences in any of the angles, radius or M1SI parameters (the first modified sacroiliac). However, one parameter (BS) of M2SI (the second modified sacroiliac), two parameters (AP and BS) of M3SI (the third modified sacroiliac), and three parameters (AP, BS, L) of M4SI (the fourth modified sacroiliac) were statistically significant (P < 0.05). The result of comparison (between genders) showed that there were no significant differences in M1SI and M2SI; in contrast, the radius, length and the α angle of M3SI and M4SI were significantly different between genders (P < 0.05), and the radius of M4SI required special attention. If the radius of the limiting screw channel was > 3.50 mm, 52 cases (52%, 24 males and 28 females) could not complete the M4SI screw placement among 100 samples. If the radius of the limiting screw channel was > 3.0 mm, a total of 10 cases (10%, 2 males and 8 females) could not complete the M4SI screw placement.

Conclusion

Through the measurement of 100 healthy adult real three-dimensional pelvic models, we obtained the parameters of each modified sacroiliac screw and measured the three angles of each screw based on international coordinates for the first time, which can instruct clinical application.
Comparison of extended segmentectomy with traditional segmentectomy for stage I lung cancer
Authors: Cheng Ya-Fu , Hsieh Yueh-Che , Chang Yu-Jun , Cheng Ching-Yuan , Huang Chang-Lun , Hung Wei-Heng , Wang Bing-Yen
Published: March 2022

Background

For stage I non-small cell lung cancer (NSCLC), lobectomy and segmentectomy are still controversial operations. Extended segmentectomy was proposed to make larger safe margins than segmentectomy. Image-guided video-assisted thoracoscopic surgery (iVATS) is useful to accomplish extended segmentectomy. We aimed to compare the effects of iVATS extended segmentectomy to the effects of traditional segmentectomy for stage I NSCLC.

Methods

This study is a retrospective analysis in a single institute. Patients with stage I NSCLC who received segmentectomy between January 2017 and September 2020 were included. Patients were distributed to iVATS extended segmentectomy (group A), and traditional segmentectomy (group B). The impacts of the different surgical methods on resection margin were assessed.

Results

There were 116 patients enrolled in this study. Sixty-two patients distributed in group A, and the other 54 patients in group B. The resection margin to a staple line was 17.94 mm in group A versus 14.15 mm in group B, p = 0.037. The margin/tumor diameter ratio was 2.08 in group A versus 1.39 in group B, p = 0.003. The enough margin rate was 75.81% and 57.41%, respectively, for group A and group B. The subgroup analysis of iVATS extended segmentectomy showed that T1a lesions had larger margin distances than did T1b lesions (19.85 mm vs. 14.83 mm, p = 0.026).

Conclusions

The iVATS extended segmentectomy can provide more resection margin than traditional segmentectomy. Segmentectomy is more suitable to perform when the nodule’s diameter is less than 10 mm.
Thoracic endovascular aortic repair with a right thoracotomy approach
Authors: Tanioka Hideki , Shibukawa Takanori , Iwata Keiji
Published: March 2022

Background

The common femoral artery is usually the preferred access route for thoracic endovascular aortic repair (TEVAR). However, if access from the common femoral artery is challenging, other routes must be considered. We report a case of TEVAR performed by approaching the descending thoracic aorta with a right thoracotomy and using the descending thoracic aorta as an access route.

Case presentation

A 70-year-old female was diagnosed with a descending thoracic aortic aneurysm (65 mm in diameter), a thoracoabdominal aneurysm (54 mm in diameter), and an abdominal aortic aneurysm (49 mm in diameter). Since the patient had severe chronic obstructive pulmonary disease, one-stage replacement of the thoracoabdominal aortic aneurysm was contraindicated and TEVAR on the descending aorta was selected. A strong tortuous section of the aorta—from the descending aorta to the abdominal aorta—hampered endovascular access to the site from the common femoral artery. A TEVAR approach from the abdominal aorta was also considered; however, an abdominal aortic aneurysm and a transverse colon loop stoma from an earlier surgery presented challenges to this technique. We chose to access the descending thoracic aorta with a thoracotomy from the right 6th intercostal space for TEVAR, because the access route that is not affected by the meandering of the aorta is considered to be the descending aorta with a right thoracotomy. The patient’s postoperative course was uneventful after the stent graft was placed. No complications were detected with postoperative contrast-enhanced computed tomography (CT).

Conclusions

Our findings suggest that TEVAR can be performed by approaching the descending aorta from a right thoracotomy, if variations of vascular anatomy interfere with the more commonly used femoral artery approach.
Genetic mutation spectrum of pantothenate kinase-associated neurodegeneration expanded by breakpoint sequencing in pantothenate kinase 2 gene
Authors: Yang Dahae , Cho Sanghyun , Cho Sung Im , Kim Manjin , Seong Moon-Woo , Park Sung Sup
Published: March 2022

Background

Neurodegeneration with brain iron accumulation describes a group of rare heterogeneous progressive neurodegenerative disorders characterized by excessive iron accumulation in the basal ganglia region. Pantothenate kinase-associated neurodegeneration (PKAN) is a major form of this disease.

Results

A total of 7 unrelated patients were diagnosed with PKAN in a single tertiary center from August 2009 to February 2018. Ten variants inPANK2including three novel sequence variants and one large exonic deletion were detected. Sequencing of the breakpoint was performed to predict the mechanism of large deletion and AluSx3 and AluSz6 were found with approximately 97.3% sequence homology.

Conclusion

The findings support the disease-causing role ofPANK2and indicate the possibility that exonic deletion ofPANK2found in PKAN is mediated throughAlu-mediated homologous recombination.
Clinical classification, visual outcomes, and optical coherence tomographic features of 48 patients with posterior sympathetic ophthalmia
Authors: Zhuang Hong , Zhang Rui , Zhang Ting , Chang Qing , Xu Gezhi
Published: March 2022

Background

To investigate the clinical manifestations, visual outcomes and optical coherence tomographic (OCT) features of patients with posterior sympathetic ophthalmia (PSO).

Methods

We performed a retrospective review of 48 patients diagnosed with PSO between January 2013 and December 2019. We compared the clinical and OCT features among different clinical types of PSO.

Results

PSO could be classified into two types according to whether the fundus exhibited serous retinal detachment (SRD) or multifocal choroiditis (MFC). There were 41 patients (85.4%) with SRD and 7 patients (14.6%) with MFC. The latent period of patients with MFC was significantly longer than that of patients with SRD (P = 0.002). The final visual acuity of patients with MFC was significantly worse than that of patients with SRD (P = 0.0001). In patients with acute SRD, OCT revealed that the mean height of retinal detachment in the fovea was 528.8 ± 437.5 μm. After treatment, the retina reattached in all patients and the band structures of the outer retina were restored in most patients (92.7%). In patients with acute MFC, the OCT images revealed inflammatory lesions on the retinal pigment epithelium layer. After treatment, the OCT images showed hyperreflective fibrosis of the lesions and loss of the outer retinal band structures in all patients.

Conclusions

We found that PSO could be classified according to the presence of SRD or MFC. The visual prognosis differed significantly between these types of PSO. OCT imaging is useful for clinical classification and monitoring of retinal changes after treatment.
Transcriptomic analysis of patients with clinical suspicion of maturity-onset diabetes of the young (MODY) with a negative genetic diagnosis
Authors: Vázquez-Mosquera María E. , González-Vioque Emiliano , Barbosa-Gouveia Sofía , Bellido-Guerrero Diego , Tejera-Pérez Cristina , Martinez-Olmos Miguel A. , Fernández-Pombo Antía , Castaño-González Luis A. , Chans-Gerpe Roi , Couce María L.
Published: March 2022

Background

Diagnosis of mature-onset diabetes of the young (MODY), a non-autoimmune monogenic form of diabetes mellitus, is confirmed by genetic testing. However, a positive genetic diagnosis is achieved in only around 50% of patients with clinical characteristics of this disease.

Results

We evaluated the diagnostic utility of transcriptomic analysis in patients with clinical suspicion of MODY but a negative genetic diagnosis. Using Nanostring nCounter technology, we conducted transcriptomic analysis of 19 MODY-associated genes in peripheral blood samples from 19 patients and 8 healthy controls. Normalized gene expression was compared between patients and controls and correlated with each patient’s biochemical and clinical variables. Z-scores were calculated to identify significant changes in gene expression in patients versus controls. Only 7 of the genes analyzed were detected in peripheral blood. HADH expression was significantly lower in patients versus controls. Among patients with suspected MODY, GLIS3 expression was higher in obese versus normal-weight patients, and in patients aged < 25 versus > 25 years at diabetes onset. Significant alteration with respect to controls of any gene was observed in 57.9% of patients.

Conclusions

Although blood does not seem to be a suitable sample for transcriptomic analysis of patients with suspected MODY, in our study, we detected expression alterations in some of the genes studied in almost 58% of patients. That opens the door for future studies that can clarify the molecular cause of the clinic of these patients and thus be able to maintain a more specific follow-up and treatment in each case.
Perfect match: mTOR inhibitors and tuberous sclerosis complex
Authors: Luo Cong , Ye Wen-Rui , Shi Wei , Yin Ping , Chen Chen , He Yun-Bo , Chen Min-Feng , Zu Xiong-Bin , Cai Yi
Published: March 2022

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that presents with diverse and complex clinical features and involves multiple human systems. TSC-related neurological abnormalities and organ dysfunction greatly affect the quality of life and can even result in death in patients with TSC. It is widely accepted that most TSC-related clinical manifestations are associated with hyperactivation of the mammalian target of rapamycin (mTOR) pathway caused by loss‑of‑function mutations in TSC1 or TSC2. Remarkable progress in basic and translational research has led to encouraging clinical advances. Although mTOR inhibitors (rapamycin/everolimus) demonstrate great potential in TSC management, two major concerns hamper their generalized application. One is the frequent manifestation of adverse events, such as stomatitis, infections, and menstrual disorders; and the other is the poor response in certain patients. Thus, indicators are required to effectively predict the efficacy of mTOR inhibitors. Herein, we have summarized the current utilization of mTOR inhibitors in the treatment of TSC and focused on their efficacy and safety, in an attempt to provide a reference to guide the treatment of TSC.
Learn, Engage, Act, Dedicate (LEAD): development and feasibility testing of a task-shifted intervention to improve alcohol use, depression and family engagement for fathers
Authors: Giusto Ali M. , Ayuku David , Puffer Eve S.
Published: March 2022

Background

Men’s depression, alcohol use, and family problems commonly co-occur to create of cluster of mental health problems. Yet, few treatments exist to address these problems, especially in low and middle-income countries (LMICs). This paper describes the development and initial feasibility and acceptability of a novel task-shifted intervention to address this cluster of men’s mental health problems with a focus on engaging and retaining men in treatment.

Methods

The intervention, Learn, Engage, Act, Dedicate (LEAD), is based in behavioral activation blended with motivational interviewing and was pilot tested in Kenya. To develop LEAD, we engaged in a community-engaged multi-step, collaborative process with local Kenyan stakeholders. LEAD was piloted with nine fathers reporting problem drinking. To assess initial feasibility and acceptability, recruitment and participation were tracked and descriptive statistics were generated given engagement of men was key for proof of concept. Semi-structured interviews were conducted with participants and analyzed using thematic content analysis.

Results

The development process resulted in a weekly 5-session intervention rooted in behavioral activation, motivational interviewing, and masculinity discussion strategies. These approaches were combined and adapted to fit contextually salient constructs, such as the importance of the man as provider, and streamlined for lay providers. Feasibility and acceptability results were promising with high attendance, acceptability of delivery and intervention content, and perceived intervention helpfulness.

Conclusion

Results describe an acceptable task-shifted treatment that may engage men in care and addresses a cluster of common mental health problems among men in ways that consider social determinants like masculinity. Findings set the stage for a larger trial.

Trial registration ISRCTN, ISRCTN130380278. Registered 7 October 2019—Retrospectively registered, http://www.isrctn.com/ISRCTN13038027
HIV related stigma associated with social support, alcohol use disorders, depression, anxiety, and suicidal ideation among people living with HIV: a systematic review and meta-analysis
Authors: Armoon Bahram , Fleury Marie-Josée , Bayat Amir-Hossein , Fakhri Yadollah , Higgs Peter , Moghaddam Ladan Fattah , Gonabadi-Nezhad Leila
Published: March 2022

Background

Stigma is a social phenomenon known to have a negative impact on the lives of people living with HIV (PLWH). However, defining HIV-related stigma (HRS) is difficult because of the intersection it has with structural inequalities, and cultural differences, discrimination by health care providers that measure stigma among PLWH. HIV/AIDS has been characterized as a traumatic experience and PLWH may experience stigma which can cause negative mental health disorders and experiences, including emotional distress, shame, depression, anxiety, suicidal ideation. A systematic review of the evidence on the mental disorders of PLWH is currently lacking. This study aimed to analyze the association between HRS and social support, alcohol use disorders and mental health disorders and experiences (depression, anxiety, and suicidal ideation) among PLWH.

Methods

In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) this study searched PubMed, Scopus, Web of sciences, PsycInfo, SciELO and Cochrane library electronic databases to identify publications between January 1992 and August 2020 that discussed social support, alcohol use disorders, mental health disorders and experiences (i.e., depression and anxiety and suicidal ideation) associated with HRS. Pooled Odds Ratios (ORs) were utilized at a 95% confidence level, and as sampling methods differed between articles pooled estimates used a random effects model.

Results

Twenty-two studies with 9548 participants met the eligibility criteria. No association was observed between HRS and alcohol use disorders. PLWH who had higher levels of social supports were less likely to report HRS. Participants who had been diagnosed with anxiety were 1.89 times more likely to report HRS, while those diagnosed with depression were 1.61 times more. Respondents who reported suicidal ideation also were 1.83 times more likely to report HRS.

Conclusions

This meta-analysis supports that HRS has a detrimental association with anxiety, depression and suicidal ideation, but social support protects again HRS in PLWH. Applying interventions which focus on the mental health disorders of PLWH may decrease HRS. Provision of social support by practitioners, combined with mental health treatment and assessments, and designing methods to identify stigma at different stages of illness are warranted.
Circadian rhythms and cancers: the intrinsic links and therapeutic potentials
Authors: Zhou Li , Zhang Zhe , Nice Edouard , Huang Canhua , Zhang Wei , Tang Yong
Published: March 2022

The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep–wake cycles, eating–fasting cycles, and activity–rest cycles, coordinating the behavior and physiology of all organs for whole-body homeostasis. Acute disruption of circadian rhythm may lead to transient discomfort, whereas long-term irregular circadian rhythm will result in the dysfunction of the organism, therefore increasing the risks of numerous diseases especially cancers. Indeed, both epidemiological and experimental evidence has demonstrated the intrinsic link between dysregulated circadian rhythm and cancer. Accordingly, a rapidly increasing understanding of the molecular mechanisms of circadian rhythms is opening new options for cancer therapy, possibly by modulating the circadian clock. In this review, we first describe the general regulators of circadian rhythms and their functions on cancer. In addition, we provide insights into the mechanisms underlying how several types of disruption of the circadian rhythm (including sleep–wake, eating–fasting, and activity–rest) can drive cancer progression, which may expand our understanding of cancer development from the clock perspective. Moreover, we also summarize the potential applications of modulating circadian rhythms for cancer treatment, which may provide an optional therapeutic strategy for cancer patients.
Interstitial deletions of chromosome 1p: novel 1p31.3p22.2 microdeletion in a newborn with craniosynostosis, coloboma and cleft palate, and review of the genomic and phenotypic profiles
Authors: Serra Gregorio , Antona Vincenzo , Giuffrè Mario , Piro Ettore , Salerno Sergio , Schierz Ingrid Anne Mandy , Corsello Giovanni
Published: March 2022

Background

Rearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynostosis, dysmorphic face, ocular defects, cleft palate, urinary tract anomalies and hand/foot abnormalities.

Case presentation

Hereby, we report on an Italian female newborn with craniosynostosis, facial dysmorphisms including bilateral microphthalmia and coloboma, cleft palate, and a severe global developmental and growth delay, associated to a 1p31.3p22.2 deletion of 20.7 Mb. This was inherited from the healthy mother, who was carrier of a smaller (2.6 Mb) deletion included within the centromeric region (1p22.3p22.2) of the same rearrangement, in addition to a translocation between chromosomes 1p and 4q. The deleted region of the proband contains about ninety genes. We focus on the genotype–phenotype correlations.

Conclusions

The results of the present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome. It is hard to establish whether the critical rearrangement of such syndrome may involve the centromeric band p22.3p22.2, or more likely do not, also in light of the genomic profile of the healthy mother of our patient. Neonatologists and pediatricians should take into consideration 1p31 microdeletion in cases of developmental and growth delay associated to craniosynostosis, peculiar facial dysmorphisms, cleft palate and hand/foot abnormalities. The present report provides new data about 1p31 microdeletion syndrome, in view of a better characterization of its genomic and phenotypic profile.
Prospective preference assessment for the Comparison of Analgesic Regimen Effectiveness and Safety in Surgery (CARES) trial
Authors: Hyung Brian , Bicket Mark C. , Brull Richard , Pazmino-Canizares Janneth , Bozak Didem , Ladha Karim S.
Published: March 2022

Background

Clinical trials face major barriers such as under-enrollment and selective enrollment, which threaten study completion and undermine validity and generalizability. Thus, we conducted a prospective preference assessment (PPA) prior to commencing the Comparison of Analgesic Regimen Effectiveness and Safety in Surgery (CARES) trial—a randomized controlled study comparing the outcomes of managing acute postoperative pain between opioid-sparing and opioid-based therapies. This PPA aimed to (1) determine the patients’ willingness to participate in the CARES trial, (2) identify the areas for improvement, and (3) assess the differences between willing and unwilling patients.

Methods

Patients undergoing elective laparoscopic cholecystectomy were recruited between August 2019 and February 2020 from two academic hospitals. A survey was administered to each patient consisting of (1) a vignette describing the trial, (2) an assessment of the patients’ understanding of the trial, (3) open-ended questions assessing the attitudes towards the trial, and (4) patient-completed questionnaires. Data were analyzed qualitatively with thematic analysis and quantitatively with the Wilcoxon signed-rank and chi-square tests.

Results

Forty-two patients were enrolled and grouped based on the 6-point Likert scale into willing (4–6, 71%) and not willing (1–3, 29%) to participate in the CARES trial. There were no significant differences with respect to all variables: age, education, sex, visible minority status, previous research, previous surgery, regular use of pain medications, surgical concerns, previous discussions on pain management, significant pain within the past 3 months, and significant use of pain medication within the past month. Factors that motivated participation were contributing to scientific research (45%), altruism (29%), and improving personal pain (24%). Common discouraging factors were negative perceptions of opioids (29%), side effects (21%), being blinded to the study medication (21%), and poor pain management (19%).

Conclusions

This PPA revealed that two key discouraging factors for patients were being blinded to the type of pain medication being taken and the potential for poor pain management as a consequence of participation. Modifications to improve patient acceptance of the CARES trial include ensuring sufficient rescue medicine and follow-up visits consistent with current standards of care for all patients, as well as patient education surrounding safe administration and side effects of the study medications.
Methyl-qPCR: a new method to investigate Epstein–Barr virus infection in post-transplant lymphoproliferative diseases
Authors: Borde Chloé , Quignon Frédérique , Amiel Corinne , Gozlan Joël , Marechal Vincent , Brissot Eolia
Published: March 2022

Epstein–Barr virus DNA viral load is used as a surrogate marker to start Rituximab in transplant recipients at risk of developing PTLD. However, an elevated EBV DNAemia does not discriminate lymphoproliferation and replication. We designed a new molecular assay (methyl-qPCR) to distinguish methylated versus unmethylated viral genomes. In blood, viral genomes were highly methylated in EBV primary infections, PTLD and 4/5 transplant recipients with high viral load. The only patient with under-methylated EBV genomes did not respond to rituximab. Methyl-qPCR is a convenient method to discriminate between latent and lytic EBV genomes and could be useful in treatment decisions.
Current status of clinical trials assessing mesenchymal stem cell therapy for graft versus host disease: a systematic review
Authors: Li Ying , Hao Jie , Hu Zheng , Yang Yong-Guang , Zhou Qi , Sun Liguang , Wu Jun
Published: March 2022

Background

Graft-versus-host disease (GVHD) is a common fatal complication of hematopoietic stem cell transplantation (HSCT), where steroids are used as a treatment option. However, there are currently no second-line treatments for patients that develop steroid-resistance (SR). Mesenchymal stem cells (MSCs) have immunomodulatory functions and can exert immunosuppressive effects on the inflammatory microenvironment. A large number of in vitro experiments have confirmed that MSCs can significantly inhibit the proliferation or activation of innate and adaptive immune cells. In a mouse model of GVHD, MSCs improved weight loss and increased survival rate. Therefore, there is great promise for the clinical translation of MSCs for the prevention or treatment of GVHD, and several clinical trials have already been conducted to date.

Main body

In this study, we searched multiple databases and found 79 clinical trials involving the use of MSCs to prevent or treat GVHD and summarized the characteristics of these clinical trials, including study design, phase, status, and locations. We analyzed the results of these clinical trials, including the response and survival rates, to enable researchers to obtain a comprehensive understanding of the field’s progress, challenges, limitations, and future development trends. Additionally, factors that might result in inconsistencies in clinical trial results were discussed.

Conclusion

In this study, we attempted to analyze the clinical trials for MSCs in GVHD, identify the most suitable group of patients for MSC therapy, and provide a new perspective for the design of such trials in the future.