bluuebunny/crossref_metadata_2025 huggingface dataset:
REDuction of Antibiotic RESistance (REDARES) in urinary tract infections using treatments according to national clinical guidelines: study protocol for a pragmatic randomized controlled trial with a multimodal intervention in primary care
Authors: Gágyor Ildikó , Greser Alexandra , Heuschmann Peter , Rücker Viktoria , Maun Andy , Bleidorn Jutta , Heintze Christoph , Jede Felix , Eckmanns Tim , Klingeberg Anja , Mentzel Anja , Schmiemann Guido
Published: September 2021

Background

Urinary tract infections (UTIs) are a common cause of prescribing antibiotics in family medicine. In Germany, about 40% of UTI-related prescriptions are second-line antibiotics, which contributes to emerging resistance rates. To achieve a change in the prescribing behaviour among family physicians (FPs), this trial aims to implement the guideline recommendations in German family medicine.

Methods/design

In a randomized controlled trial, a multimodal intervention will be developed and tested in family practices in four regions across Germany. The intervention will consist of three elements: information on guideline recommendations, information on regional resistance and feedback of prescribing behaviour for FPs on a quarterly basis. The effect of the intervention will be compared to usual practice. The primary endpoint is the absolute difference in the mean of prescribing rates of second-line antibiotics among the intervention and the control group after 12 months. To detect a 10% absolute difference in the prescribing rate after one year, with a significance level of 5% and a power of 86%, a sample size of 57 practices per group will be needed. Assuming a dropout rate of 10%, an overall number of 128 practices will be required. The accompanying process evaluation will provide information on feasibility and acceptance of the intervention.

Discussion

If proven effective and feasible, the components of the intervention can improve adherence to antibiotic prescribing guidelines and contribute to antimicrobial stewardship in ambulatory care. 

Trial registration DRKS, DRKS00020389, Registered 30 January 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020389.
Re-emergence of syphilis in women of reproductive age and its association with the increase in congenital syphilis in Mexico during 2010–2019: an ecological study
Authors: García-Cisneros Santa , Herrera-Ortiz Antonia , Olamendi-Portugal Maria , Sánchez-Alemán Miguel Angel
Published: September 2021

Background

Syphilis is a sexually transmitted infection that is re-emerging in different parts of the world. This infection can be transmitted during pregnancy, causing neonatal syphilis. The objective of this study was to examine trend in syphilis, congenital syphilis, and neonatal deaths among the Mexican population during 2010–2019.

Methods

An ecological study was carried out to collect information about the incidence of syphilis, the incidence of congenital syphilis, and the incidence of neonatal death from congenital syphilis. The variables were described considering age, sex, Mexican state, and year. Trends across time (calendar year) were analyzed using linear regression, increases were estimated with 95% confidence intervals, and p < 0.05 was considered statistically significant.

Results

The incidence of syphilis increased by an average of 0.336 cases/100,000 per year and was higher among women aged 15–19 years (0.693 cases). Cases of congenital syphilis increased from 62 cases in 2010 to 372 cases in 2019; furthermore, the increase in syphilis cases among women aged 20 to 24 years was associated with an increase in cases of congenital syphilis. In 2010, 50% of Mexican states did not report cases of congenital syphilis, but in 2018, only 10% did not report cases of congenital syphilis. Between 2010 and 2018, 83 neonatal deaths were reported, with the highest incidence in 2018 (0.88 deaths/100,000 newborns).

Conclusion

The incidence of congenital syphilis is increasing in Mexico. As a consequence of the reemergence of syphilis among the population of reproductive age, it is necessary to address and treat syphilis in various population groups.
Changes in magnetic resonance imaging relaxation time on postmortem magnetic resonance imaging of formalin-fixed human normal heart tissue
Authors: Ebata Kiyokadzu , Noriki Sakon , Inai Kunihiro , Kimura Hirohiko
Published: September 2021

Background

Postmortem magnetic resonance imaging (MRI) has been used to investigate the cause of death, but due to time constraints, it is not widely applied to the heart. Therefore, MRI analysis of the heart after formalin fixation was previously performed. However, the changes in MRI signal values based on the fixation time of formalin were not investigated. The objective was to investigate changes over time in the T1- and T2-values of MRI signals in normal areas of hearts removed during autopsy, hearts subsequently fixed in formalin, and heart specimens sliced for the preparation of pathological specimens.

Methods

The study subjects were 21 autopsy cases in our hospital between May 26, 2019 and February 16, 2020 whose hearts were removed and scanned by MRI. The male:female ratio was 14:7, and their ages at death ranged from 9 to 92 years (mean age 65.0 ± 19.7 years). Postmortem (PM)-MRI was conducted with a 0.3-Tesla (0.3-T) scanner containing a permanent magnet. A 4-channel QD head coil was used as the receiver coil. Scans were performed immediately after removal, post-formalin fixation, and after slicing; 7 cases were scanned at all three time points.

Results

The T1- and T2-values were calculated from the MRI signals of each sample organ at each scanning stage. Specimens were sliced from removed organs after formalin fixation, and the changes in T1- and T2-values over time were graphed to obtain an approximate curve. The median T1-values at each measurement time point tended to decrease from immediately after removal. The T2-values showed the same tendency to decrease, but this tendency was more pronounced for the T1-values.

Conclusion

MRI signal changes in images of heart specimens were investigated. Formalin fixation shortened both T1- and T2-values over time, and approximation formulae were derived to show these decreases over time. The shortening of T1- and T2-values can be understood as commensurate with the reduction in the water content (water molecules) of the formalin-fixed heart.
Periphery kinetic perimetry: clinically feasible to complement central static perimetry
Authors: Ma Xiaoxiao , Tang Li , Chen Xiaoming , Zeng Liuzhi
Published: September 2021

Background

Existing evidence suggests that visual field defect in eyes with glaucoma significantly varies between individuals. The following study compared the central visual field defects with the peripheral visual field defects in patients with suspect glaucoma and primary open-angle glaucoma (POAG) and investigated whether using the central visual field test alone could result in loss of clinically valuable information.

Methods

In this prospective observational study, 167 eyes from 89 patients with suspect glaucoma or POAG were first examined with static automated perimetry (SAP), followed by a peripheral visual field test on Octopus 900 perimeter (Haag-Streit, Koeniz, Switzerland). The peripheral visual field test was performed by “Auto Kinetic Perimetry” program, in which Goldmann III4e stimuli randomly moved along 16 vectors at a constant angular velocity of 5 deg/s.

Results

Glaucomatous peripheral visual field defects were seen in 18% of the eyes with a normal central visual field. In addition, 86% of glaucoma patients with moderate-to-severe central visual field defects had corresponding peripheral visual field defects in the form of localized or diffuse depression of the isopters. Furthermore, a moderate correlation was found between the central and peripheral visual fields. The median test duration was 71 s for the peripheral test and 803 s for the central test (p < 0.001).

Conclusions

Our study demonstrated the diversity of glaucomatous visual field defects, as well as the possibility of losing the clinically valuable information due to focusing on the central visual field test alone. The peripheral kinetic perimetry is clinically feasible to complement the central static perimetry for a comprehensive assessment of visual function in glaucoma patients.
No difference in the incidence or location of deep venous thrombosis according to use of pharmacological prophylaxis following total knee arthroplasty
Authors: Itou Junya , Kuwashima Umito , Itoh Masafumi , Okazaki Ken
Published: September 2021

Background

The incidence and characteristics of deep vein thrombosis (DVT) following total knee arthroplasty (TKA) without pharmacologic prophylaxis have not been fully investigated. This study aimed to determine whether there are any differences in the incidence, location, and characteristics of DVT following TKA with pharmacologic prophylaxis and without pharmacologic prophylaxis.

Methods

A total of 156 knees were retrospectively evaluated for DVT following TKA by duplex ultrasound on postoperative day 7, after excluding 60 knees from 216 consecutive knees because of antiplatelet or anticoagulant use before surgery, history of venous thromboembolism, or bleeding risk. The 156 knees included in the analysis were divided into two groups: with pharmacologic prophylaxis (n = 79) and without pharmacologic prophylaxis (n = 77).

Results

The overall incidence of DVT was 34% (54/156 knees). DVT was detected in 31.6% of knees with pharmacologic prophylaxis and in 37.6% of knees without pharmacologic prophylaxis; the difference was not statistically significant. Soleal vein thrombus was observed in 74.6% of the knees with DVT and non-floating thrombus was observed in 98.7%. There were no obvious between-group differences in thrombus characteristics such as compressibility, echogenicity, mean vein diameter, and whether the thrombus was attached to the vein wall or free-floating.

Conclusions

No differences were found in the incidence, location, or characteristics of DVT following TKA with or without pharmacological prophylaxis.
Treatment of humeral shaft fractures: a new minimally-invasive plate osteosynthesis versus open reduction and internal fixation: a case control study
Authors: Yang Jing , Liu Dapeng , Zhang Lina , Lu Zhanxin , Liu Tang , Tao Cheng
Published: September 2021

Background

To evaluate the feasibility and safety of a new minimally-invasive surgical approach–anteromedial minimally-invasive plate osteosynthesis (MIPO)–in the treatment of middle and distal humeral shaft fractures.

Methods

Fourteen patients with humeral shaft fracture treated with anteromedial MIPO from November 2016 to March 2020 (MIPO Group) were selected as the study subjects. Open reduction and internal fixation (ORIF) were used to treat 14 patients with humeral shaft fractures as the control group (ORIF group). The two groups were fixed with a locking compression plate (LCP) or LCP + multi-directional locking screw system (MDLS). The incision length, intraoperative blood loss, intraoperative fluoroscopy time, operation time, length of hospital stay, fracture healing time, QuickDASH score and Constant score were observed and compared between the two groups.

Results

Fourteen patients were enrolled in each group. The incision length (7.79 ± 2.39 cm), intraoperative blood loss (96.07 ± 14.96 mL), operative time (110.57 ± 21.90 min), hospital stay (6.29 ± 1.49 days) and fracture healing time (14.94 ± 0.99 weeks) in the MIPO group were all lower than those in the ORIF group, and the difference was statistically significant for each parameter (P < 0.05). The intraoperative fluoroscopy time (20.07 ± 3.22) in the MIPO group was significantly higher than that in the ORIF group (P < 0.05). There were no significant differences in age (P = 0.078), QuickDASH score (P = 0.074) or Constant score (P = 0.293) between the two groups and no postoperative complications occurred in any of the patients.

Conclusion

The anteromedial approach MIPO technique has the advantages of less trauma, less bleeding, low risk of nerve injury and high rate of fracture healing. It is one of the most effective methods for the treatment of middle and middle–distal humeral shaft fractures.
Physical functioning and mental health treatment initiation and retention for veterans with posttraumatic stress disorder: a prospective cohort study
Authors: Duan-Porter Wei , Nelson David B. , Ensrud Kristine E. , Spoont Michele R.
Published: September 2021

Background

Most US adults with posttraumatic stress disorder (PTSD) do not initiate mental health treatment within a year of diagnosis. Increasing treatment uptake can improve health and quality of life for those with PTSD. Individuals with PTSD are more likely to report poor physical functioning, which may contribute to difficulty with treatment initiation and retention. We sought to determine the effects of poor physical functioning on mental health treatment initiation and retention for individuals with PTSD.

Methods

We used data for a national cohort of veterans in VA care; diagnosed with PTSD in June 2008-July 2009; with no mental health treatment in the prior year; and who responded to baseline surveys on physical functioning and PTSD symptoms (n = 6,765). Physical functioning was assessed using Veterans RAND 12-item Short Form Health Survey, and encoded as limitations in physical functioning and role limitations due to physical health. Treatment initiation (within 6 months of diagnosis) was determined using VA data and categorized as none (reference), only medications, only psychotherapy, or both. Treatment retention was defined as having ≥ 4 months of appropriate antidepressant or ≥ 8 psychotherapy encounters.

Results

In multinomial models, greater limitations in physical functioning were associated with lower odds of initiating only psychotherapy (OR 0.82 [95 % CI 0.68, 0.97] for limited a little and OR 0.74 [0.61, 0.90] for limited a lot, compared to reference “Not limited at all”). However, it was not associated with initiation of medications alone (OR 1.04 [0.85, 1.28] for limited a little and OR 1.07 [0.86, 1.34] for limited a lot) or combined with psychotherapy (OR 1.03 [0.85, 1.25] for limited a little and OR 0.95 [0.78, 1.17] for limited a lot). Greater limitations in physical functioning were also associated with lower odds of psychotherapy retention (OR 0.69 [0.53, 0.89] for limited a lot) but not for medications (e.g., OR 0.96 [0.79, 1.17] for limited a lot). Role limitations was only associated with initiation of both medications and psychotherapy, but there was no effect gradient (OR 1.38 [1.03, 1.86] for limitations a little or some of the time, and OR 1.18 [0.63, 1.06] for most or all of the time, compared to reference “None of the time”). Accounting for chronic physical health conditions did not attenuate associations between limitations in physical functioning (or role limitations) and PTSD treatment; having more chronic conditions was associated with lower odds of both initiation and retention for all treatments (e.g., for 2 + conditions OR 0.53 [0.41, 0.67] for initiation of psychotherapy).

Conclusions

Greater limitations in physical functioning may be a barrier to psychotherapy initiation and retention. Future interventions addressing physical functioning may enhance uptake of psychotherapy.
Self-organising human gonads generated by a Matrigel-based gradient system
Authors: Oliver Elizabeth , Alves-Lopes João Pedro , Harteveld Femke , Mitchell Rod T. , Åkesson Elisabet , Söder Olle , Stukenborg Jan-Bernd
Published: September 2021

Background

Advances in three-dimensional culture technologies have led to progression in systems used to model the gonadal microenvironment in vitro. Despite demonstrating basic functionality, tissue organisation is often limited. We have previously detailed a three-dimensional culture model termed the three-layer gradient system to generate rat testicular organoids in vitro. Here we extend the model to human first-trimester embryonic gonadal tissue.

Results

Testicular cell suspensions reorganised into testis-like organoids with distinct seminiferous-like cords situated within an interstitial environment after 7 days. In contrast, tissue reorganisation failed to occur when mesonephros, which promotes testicular development in vivo, was included in the tissue digest. Organoids generated from dissociated female gonad cell suspensions formed loosely organised cords after 7 days. In addition to displaying testis-specific architecture, testis-like organoids demonstrated evidence of somatic cell differentiation. Within the 3-LGS, we observed the onset of AMH expression in the cytoplasm of SOX9-positive Sertoli cells within reorganised testicular cords. Leydig cell differentiation and onset of steroidogenic capacity was also revealed in the 3-LGS through the expression of key steroidogenic enzymes StAR and CYP17A1 within the interstitial compartment. While the 3-LGS generates a somatic cell environment capable of supporting germ cell survival in ovarian organoids germ cell loss was observed in testicular organoids.

Conclusion

The 3-LGS can be used to generate organised whole gonadal organoids within 7 days. The 3-LGS brings a new opportunity to explore gonadal organogenesis and contributes to the development of more complex in vitro models in the field of developmental and regenerative medicine.
Glycerol or crude glycerol as substrates make Pseudomonas aeruginosa achieve anaerobic production of rhamnolipids
Authors: Zhao Feng , Wu Yuting , Wang Qingzhi , Zheng Mengyao , Cui Qingfeng
Published: September 2021

Background

The anaerobic production of rhamnolipids is significant in research and application, such as foamless fermentation and in situ production of rhamnolipids in the anoxic environments. Although a few studies reported that some rare Pseudomonas aeruginosa strains can produce rhamnolipids anaerobically, the decisive factors for anaerobic production of rhamnolipids were unknown.

Results

Two possible hypotheses on the decisive factors for anaerobic production of rhamnolipids by P. aeruginosa were proposed, the strains specificity of rare P. aeruginosa (hypothesis 1) and the effect of specific substrates (hypothesis 2). This study assessed the anaerobic growth and rhamnolipids synthesis of three P. aeruginosa strains using different substrates. P. aeruginosa strains anaerobically grew well using all the tested substrates, but glycerol was the only carbon source that supported anaerobic production of rhamnolipids. Other carbon sources with different concentrations still failed for anaerobic production of rhamnolipids by P. aeruginosa. Nitrate was the excellent nitrogen source for anaerobic production of rhamnolipids. FTIR spectra analysis confirmed the anaerobically produced rhamnolipids by P. aeruginosa using glycerol. The anaerobically produced rhamnolipids decreased air-water surface tension to below 29.0 mN/m and emulsified crude oil with EI24 above 65%. Crude glycerol and 1, 2-propylene glycol also supported the anaerobic production of rhamnolipids by all P. aeruginosa strains. Prospects and bottlenecks to anaerobic production of rhamnolipids were also discussed.

Conclusions

Glycerol substrate was the decisive factor for anaerobic production of rhamnolipids by P. aeruginosa. Strain specificity resulted in the different anaerobic yield of rhamnolipids. Crude glycerol was one low cost substrate for anaerobic biosynthesis of rhamnolipids by P. aeruginosa. Results help advance the research on anaerobic production of rhamnolipids, deepen the biosynthesis theory of rhamnolipids and optimize the anaerobic production of rhamnolipids.
Successful transplantation of spermatogonial stem cells into the seminiferous tubules of busulfan-treated mice
Authors: Azizi Hossein , Niazi Tabar Amirreza , Skutella Thomas
Published: September 2021

Background

Spermatogonial stem cells (SSCs) in the testis are crucial for transferring genetic information to the next generation. Successful transplantation of SSCs to infertile men is an advanced therapeutic application in reproductive biology research.

Methods

In this experimental research, both in vitro and in vivo characterization of undifferentiated and differentiated SSCs were performed by morphology—immunocytochemistry (ICC), immunohistochemistry (IMH), Fluidigm Real-Time polymerase chain reaction (RT-PCR) and flow cytometry analysis. The isolated SSCs were finally microinjected into the rete testis of busulfan-treated mice.

The compact undifferentiated and more loosely connected round differentiated SSCs were isolated during testicular cell expansion from their specific feeder layer.

Results

ICC analysis indicated high and low expression levels of Zbtb16 in undifferentiated and differentiated germ cells. Also, IMH analysis showed different expression levels of Zbtb16 in the two different germ stem cell populations of the testicular tissue. While Fluidigm RT-PCR analysis indicated overexpression of the TAF4B germ cell gene, the expression of DAZL, VASA, and Zbtb16 were down-regulated during the differentiation of SSCs (P < 0.05). Also, flow cytometry analysis confirmed the significant downregulation of Itgb1 and Itga4 during differentiation. By transplantation of SSCs into busulfan-treated NOD/SCID mice, GFP-labeled sperm cells developed.

Conclusions

In the current study, we performed a transplantation technique that could be useful for the future microinjection of SSCs during infertility treatment and for studying in vivo differentiation of SSCs into sperm.
Human adenoviruses in paediatric patients with respiratory tract infections in Beijing, China
Authors: Huang Yiman , Wang Chao , Ma Fenlian , Guo Qiong , Yao Lihong , Chen Aijun , Luo Xiaoyi , Zheng Lishu
Published: September 2021

Background

Human adenoviruse (HAdV) is a major pathogen of paediatric respiratory tract infections (RTIs). Mutation or recombination of HAdV genes may cause changes in its pathogenicity and transmission. We described the epidemiology and genotypic diversity of HAdV in hospitalized children with RTIs in Beijing, China.

Methods

Nasopharyngeal aspirates were collected from hospitalized children with RTIs from April 2018 to March 2019. HAdVs were detected by a quantitative real-time PCR, and the hexon gene was used for phylogenetic analysis.

Results

Among 1572 samples, 90 (5.72%) were HAdV-positive. The HAdV detection rate was highest in November and July. Among HAdV-positive children, 61.11% (55/90) were co-infected with other respiratory viruses, the most common of which were human respiratory syncytial virus and human rhinovirus. The main diagnosis was bronchopneumonia, most patient have cough and fever. Children with a high viral load were more likely to have a high fever (P = 0.041) and elevated WBC count (P = 0.000). Of 55 HAdV-positive specimens, HAdV-B (63.64%), HAdV-C (27.27%), and HAdV-E (9.09%) were main epidemic species. Phylogenetic analysis indicated that hexon sequences of three samples were on the same branch with the recombinant HAdV strain (CBJ113), which was circulating in Beijing since 2016.

Conclusion

The HAdV-B3 and HAdV-B7 are the main epidemic strains in Beijing, and the recombinant HAdV-C strain CBJ113 has formed an epidemic trend.
Priorities for addressing substance use disorder in humanitarian settings
Authors: Greene M. Claire , Haddad Stephanie , Busse Anja , Ezard Nadine , Ventevogel Peter , Demis Lina , Inoue Sachi , Gumm Jan-Christopher , Campello Giovanna , Tol Wietse A. , Kane Jeremy C.
Published: September 2021

Background

Populations affected by humanitarian emergencies are vulnerable to substance (alcohol and other drug) use disorders, yet treatment and prevention services are scarce. Delivering substance use disorder treatment services in humanitarian settings is hampered by limited guidance around the preparation, implementation, and evaluation of substance use disorder treatment programs. This study aims to identify and prioritize key gaps and opportunities for addressing substance use disorder in humanitarian settings.

Methods

UNODC convened a consultation meeting (n = 110) in coordination with UNHCR and WHO and administered an online survey (n = 34) to, thirteen program administrators and policymakers, eleven service providers, nine researchers, and one person with lived experience to explore best practices and challenges to addressing substance use disorder in diverse populations and contexts. Participants presented best practices for addressing substance use disorder, identified and ranked challenges and opportunities for improving the delivery of substance use disorder treatment interventions, and provided recommendations for guidelines that would facilitate the delivery of substance use disorder treatment services in humanitarian emergencies.

Results

Participants agreed on key principles for delivering substance use disorder treatment in humanitarian settings that centered on community engagement and building trust, integrated service delivery models, reducing stigma, considering culture and context in service delivery, and an ethical ‘do no harm’ approach. Specific gaps in knowledge that precluded the delivery of appropriate substance use disorder treatment include limited knowledge of the burden and patterns of substance use in humanitarian settings, the effectiveness of substance use disorder treatment services in humanitarian settings, and strategies for adapting and implementing interventions for a given population and humanitarian context. Participants emphasized the need to strengthen awareness and commitment related to the burden of substance use disorder treatment interventions among communities, practitioners, and policymakers in humanitarian settings.

Conclusions

Results from this consultation process highlight existing gaps in knowledge related to the epidemiology and treatment of substance use disorders in humanitarian emergencies. Epidemiological, intervention, and implementation research as well as operational guidance are needed to fill these gaps and improve access to substance use treatment services in humanitarian settings.
Perceived causes of mental illness and views on appropriate care pathways among Indonesians
Authors: Anjara Sabrina Gabrielle , Brayne Carol , Van Bortel Tine
Published: September 2021

Background

The mental health system in Indonesia comprises attempts to modernise a colonial relic. There is still a disconnect between available services and help-seeking behaviours at the grassroots level. This study aims to explore the perceptions of Javanese people on the aetiology of mental illness and their ideas on how to deal with individuals who may have mental illness.

Methods

This qualitative study involves semi-structured interviews, embedded in a cluster randomised trial examining the clinical and cost-effectiveness of primary mental health services. Interviews were conducted with Indonesian and Javanese. The recruitment procedure was aligned to the trial. Participants were primary care patients recruited from 21 sites across Yogyakarta province. Interviews were recorded, transcribed, and translated into English. Thematic analysis was used to analyse the interview transcripts.

Results

75 participants took part in the study: 51 women (68%) and 24 men (32%). Key themes emerged around perceived causes of mental health problems (including ‘extrinsic factors’; ‘intrinsic factors’; and ‘spiritual factors’), and perceived appropriate pathways of care (‘modern medical science’; ‘social support and activities’; and ‘religious or spiritual interventions’). Gender potentially influenced some of the responses.

Conclusions

Themes indicate the variety of preconceptions towards mental health problems and assumptions regarding the best management pathways. Some of these preconceptions and assumptions support the utility of modern medical care, while the rest promote spiritual or religious healers. Participants’ ideas of the appropriate care pathways largely correspond to their perception of what the symptoms are caused by. Despite hints to some understanding of the bio-psycho-social model of mental illness, most participants did not capture the complexity of mental health and illness, indicating the importance of contextual (especially culturally and religiously-aligned) public education around mental health, illness and care.
Hypoxia with inflammation and reperfusion alters membrane resistance by dynamically regulating voltage-gated potassium channels in hippocampal CA1 neurons
Authors: Yang Yoon-Sil , Choi Joon Ho , Rah Jong-Cheol
Published: September 2021

Hypoxia typically accompanies acute inflammatory responses in patients and animal models. However, a limited number of studies have examined the effect of hypoxia in combination with inflammation (Hypo-Inf) on neural function. We previously reported that neuronal excitability in hippocampal CA1 neurons decreased during hypoxia and greatly rebounded upon reoxygenation. We attributed this altered excitability mainly to the dynamic regulation of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels and input resistance. However, the molecular mechanisms underlying input resistance changes by Hypo-Inf and reperfusion remained unclear. In the present study, we found that a change in the density of the delayed rectifier potassium current (IDR) can explain the input resistance variability. Furthermore, voltage-dependent inactivation of A-type potassium (IA) channels shifted in the depolarizing direction during Hypo-Inf and reverted to normal upon reperfusion without a significant alteration in the maximum current density. Our results indicate that changes in the input resistance, and consequently excitability, caused by Hypo-Inf and reperfusion are at least partially regulated by the availability and voltage dependence of KV channels. Moreover, these results suggest that selective KV channel modulators can be used as potential neuroprotective drugs to minimize hypoxia- and reperfusion-induced neuronal damage.
SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs
Authors: Rabin Avigayel , Zaffagni Michela , Ashwal-Fluss Reut , Patop Ines Lucia , Jajoo Aarti , Shenzis Shlomo , Carmel Liran , Kadener Sebastian
Published: September 2021

Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We show that SRCP is more sensitive than other individual pipelines and allows for more comprehensive quantification of a larger number of differentially expressed circRNAs. To facilitate the use of SRCP, we generate a comprehensive collection of validated circRNAs in five different organisms, including humans. We then utilize our approach and identify a subset of circRNAs bound to the miRNA-effector protein AGO2 in human brain samples.
Coordination of consolidated bioprocessing technology and carbon dioxide fixation to produce malic acid directly from plant biomass in Myceliophthora thermophila
Authors: Li Jingen , Chen Bingchen , Gu Shuying , Zhao Zhen , Liu Qian , Sun Tao , Zhang Yongli , Wu Taju , Liu Defei , Sun Wenliang , Tian Chaoguang
Published: September 2021

Background

Consolidated bioprocessing (CBP) technique is a promising strategy for biorefinery construction, producing bulk chemicals directly from plant biomass without extra hydrolysis steps. Fixing and channeling CO2 into carbon metabolism for increased carbon efficiency in producing value-added compounds is another strategy for cost-effective bio-manufacturing. It has not been reported whether these two strategies can be combined in one microbial platform.

Results

In this study, using the cellulolytic thermophilic fungus Myceliophthora thermophila, we designed and constructed a novel biorefinery system DMCC (Direct microbial conversion of biomass with CO2 fixation) through incorporating two CO2 fixation modules, PYC module and Calvin–Benson–Bassham (CBB) pathway. Harboring the both modules, the average rate of fixing and channeling 13CO2 into malic acid in strain CP51 achieved 44.4, 90.7, and 80.7 mg/L/h, on xylose, glucose, and cellulose, respectively. The corresponding titers of malic acid were up to 42.1, 70.4, and 70.1 g/L, respectively, representing the increases of 40%, 10%, and 7%, respectively, compared to the parental strain possessing only PYC module. The DMCC system was further improved by enhancing the pentose uptake ability. Using raw plant biomass as the feedstock, yield of malic acid produced by the DMCC system was up to 0.53 g/g, with 13C content of 0.44 mol/mol malic acid, suggesting DMCC system can produce 1 t of malic acid from 1.89 t of biomass and fix 0.14 t CO2 accordingly.

Conclusions

This study designed and constructed a novel biorefinery system named DMCC, which can convert raw plant biomass and CO2 into organic acid efficiently, presenting a promising strategy for cost-effective production of value-added compounds in biorefinery. The DMCC system is one of great options for realization of carbon neutral economy.
Association of sleep quality with glycemic variability assessed by flash glucose monitoring in patients with type 2 diabetes
Authors: Yang Yang , Zhao Li-hua , Li Dan-dan , Xu Feng , Wang Xiao-hua , Lu Chun-feng , Wang Chun-hua , Yu Chao , Zhang Xiu-lin , Ning Li-yan , Wang Xue-qin , Su Jian-bin , Wang Li-hua
Published: September 2021

Background

Deterioration of sleep quality has been reported to contribute to the incidence of diabetes and may be responsible for glycemic status in diabetes. The present study explored the relationship between sleep quality and glycemic variability in patients with type 2 diabetes (T2D).

Methods

We recruited 111 patients with T2D for this cross-sectional study. Each patient underwent flash glucose monitoring for 14 days to obtain glycemic variability parameters, such as standard deviation of glucose (SD), coefficient of variation of glucose (CV), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and time in glucose range of 3.9–10 mmol/L (TIR3.9–10). After 14 days of flash glucose monitoring, each patient received a questionnaire on the Pittsburgh Sleep Quality Index (PSQI) to evaluate subjective sleep quality. HbA1c was also collected to assess average glucose.

Results

HbA1c was comparable among the subgroups of PSQI score tertiles. Across ascending tertiles of PSQI scores, SD, CV and MAGE were increased, while TIR3.9–10was decreased (pfor trend  <  0.05), but not MODD (pfor trend  =  0.090). Moreover, PSQI scores were positively correlated with SD, CV, MODD and MAGE (r =  0.322, 0.361, 0.308 and 0.354, respectively,p  <  0.001) and were inversely correlated with TIR3.9–10(r  =  − 0.386,p  <  0.001). After adjusting for other relevant data by multivariate linear regression analyses, PSQI scores were independently responsible for SD (β  =  0.251,t  =  2.112,p  =  0.041), CV (β  =  0.286,t  =  2.207,p  =  0.033), MAGE (β  =  0.323,t  =  2.489,p  =  0.018), and TIR3.9–10(β  =  − 0.401,t  =  − 3.930,p  <  0.001) but not for MODD (β  =  0.188,t =  1.374,p  =  0.177).

Conclusions

Increased glycemic variability assessed by flash glucose monitoring was closely associated with poor subjective sleep quality evaluated by the PSQI in patients with T2D.
Tubulointerstitial nephritis and uveitis syndrome following meningitis and systemic lymphadenopathy with persistent Toxoplasma immunoglobulin M: a case report
Authors: Oya Yoshihiro , Futami Hidekazu , Nakazawa Takuya , Ishijima Kazuyuki , Umemiya Keiko , Takizawa Fumiyoshi , Imai Naoki , Kitamura Hiroshi , Matsumura Ryutaro
Published: September 2021

Background

Tubulointerstitial nephritis and uveitis syndrome is a rare lymphocyte-related oculorenal inflammatory disease presumed to be associated with drug use and infectious agents. Toxoplasma gondii is one of such pathogens that could exhibit encephalitis, meningitis, and uveitis in immunocompromised or in some immunocompetent individuals. If the immunoglobulin M of Toxoplasma is positive on screening, the interpretation of the result is not simple, especially when immunoglobulin M stays positive persistently.

Case presentation

A 34-year-old Asian male developed fever, headache, and lymphadenopathy with tenderness, which was initially diagnosed as meningitis. Antibiotics were started, and diclofenac sodium was used for the fever. Although his symptoms were alleviated in a week by the treatment, gradual decline in renal function was noted, prompting a renal biopsy that indicated acute granulomatous interstitial nephritis. A week later, tenderness in both eyes with blurred vision appeared and revealed iritis and keratic precipitations in both eyes; hence, the diagnosis of acute tubulointerstitial nephritis and bilateral uveitis syndrome was made. Toxoplasma gondii-specific immunoglobulin G and immunoglobulin M titers were both positive. Although we could not rule out recent infection of Toxoplasma gondii, which may cause uveitis initially, Toxoplasma immunoglobulin G avidity test indicated a distant infection, which allowed us to rule out meningitis and uveitis as responsible for the complication of recent Toxoplasma gondii infection. Drug-induced lymphocyte stimulation test, or lymphocyte transformation test of diclofenac sodium, was solely positive among the tested drugs. Uveitis was alleviated only with ophthalmic steroid, and renal function returned to normal without administration of systemic steroid.

Conclusions

We experienced a case of diclofenac-induced tubulointerstitial nephritis and uveitis syndrome. In ruling out infections, Toxoplasma immunoglobulin M was persistently positive, and Toxoplasma immunoglobulin G avidity test indicated a “distant” infection. From these two results, we ruled out recent infection. However, it should be noted that “distant” infection indicated by commercial immunoglobulin G avidity is still a multiplex profile consisting of reinfection, reactivation, and latent infection. Narrowing down the infection profile of Toxoplasma is challenging in some cases. Therefore, careful diagnosis and extended follow-up of such patients are needed.
An assemblage of giant aquatic snakes (Serpentes, Palaeophiidae) from the Eocene of Togo
Authors: Georgalis Georgios L. , Guinot Guillaume , Kassegne Koffi Evenyon , Amoudji Yawovi Zikpi , Johnson Ampah Kodjo C. , Cappetta Henri , Hautier Lionel
Published: September 2021

We here describe a monospecific assemblage of giant aquatic snakes from the middle Eocene of Kpogamé, Togo. The material, consisting of large isolated vertebrae, is referred to Palaeophis africanus, an enigmatic palaeophiid species, which was so far otherwise known only from a limited number of vertebrae from the middle Eocene of Nigeria and Angola. Material from the late Eocene of the eastern USA that had been referred to the same species, is here instead considered too fragmentary for species-level determination and Palaeophis africanus is thus so far restricted to Africa. With the aid of micro-CT scanning, we present 3D models of 17 vertebrae, pertaining to different portions of the vertebral column. We provide detailed comparisons of the new material with all named African species of the genus Palaeophis. A tentative diagnosis of Palaeophis africanus is provided. With more than 50 vertebrae, the new Togolese specimens represent the most abundant known material attributed to Palaeophis africanus and significantly enhance our knowledge of the vertebral anatomy and intracolumnar variation for this taxon. Furthermore, this adds to the, as yet, extremely scarce fossil record of squamates from central western Africa, a region where Paleogene herpetofaunas are only rather poorly known.
Imaging modalities for diagnosis and monitoring of cancer cachexia
Authors: Han Jessie , Harrison Luke , Patzelt Lisa , Wu Mingming , Junker Daniela , Herzig Stephan , Berriel Diaz Mauricio , Karampinos Dimitrios C.
Published: September 2021

Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities—that is, computed tomography, magnetic resonance imaging, (18F) fluoro-2-deoxy-d-glucose (18FDG) PET and dual-energy X-ray absorptiometry—shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.
Bifurcation curves and exact multiplicity of positive solutions for Dirichlet problems with the Minkowski-curvature equation
Authors: Gao Hongliang , Xu Jing
Published: September 2021

In this paper, we consider the bifurcation curves and exact multiplicity of positive solutions of the one-dimensional Minkowski-curvature equation
$$ \textstyle\begin{cases} - (\frac{u'}{\sqrt{1-u^{\prime \,2}}} )'=\lambda f(u), &x\in (-L,L), \\ u(-L)=0=u(L), \end{cases} $$

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Calculation of vectorial derivatives for functions of a quaternion variable and their properties
Authors: Kim Ji Eun
Published: September 2021

Various attempts have been made in defining the derivative of a quaternionic function due to the noncommutativity of the product over quaternions. We observe that the difference in the left and right operations caused by the noncommutativity of the quaternion product is determined by the vector part of the quaternion. In this paper, we propose a corresponding derivative to replace the derivative of a quaternion-valued function of a quaternionic variable using the component terms of a quaternion. Further, the analogous constant, product, and quotient rules for the proposed calculations are given. Application of the proposed derivatives is provided to compute the derivatives of elementary functions. Several illustrations are also presented.
Safety of elective abdominal and vascular surgery during the COVID-19 pandemic: a retrospective single-center study
Authors: Flemming Sven , Hankir Mohammed K. , Kusan Simon , Krone Manuel , Anger Friedrich , Germer Christoph-Thomas , Wiegering Armin
Published: September 2021

Background

Patients with coronavirus disease 2019 (COVID-19) who undergo surgery have impaired postoperative outcomes and increased mortality. Consequently, elective and semi-urgent operations on the increasing number of patients severely affected by COVID-19 have been indefinitely postponed.in many countries with unclear implications on disease progression and overall survival. The purpose of this study was to evaluate whether the establishment of a standardized screening program for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sufficient to ensure high-quality medical and surgical treatment of COVID-19 and non-COVID-19 patients while minimizing in-hospital SARS-CoV-2 transmission.

Methods

The screening program comprised polymerase chain reaction (PCR) testing of nasopharyngeal swabs and a standardized questionnaire about potential symptoms for SARS-CoV-2 infection. All elective and emergency patients admitted to the surgical department of a tertiary-care hospital center in Lower Franconia, Germany, between March and May 2020 were included and their characteristics were recorded.

Results

Out of the study population (n = 657), 509 patients (77.5%) had at least one risk factor for a potentially severe course of COVID-19 and 164 patients (25%) were active smokers. The average 7-day incidence in Lower Franconia was 24.0/100,000 during the observation period. Preoperative PCR testing revealed four asymptomatic positive patients out of the 657 tested patients. No postoperative SARS-CoV-2 infection or transmission could be detected.

Conclusion

The implementation of a standardized preoperative screening program to both COVID-19 and non-COVID-19 patients can ensure high-quality surgical care while minimizing infection risk for healthcare workers and potential in-hospital transmission.
User experiences and perceptions of health wearables: an exploratory study in Cambodia
Authors: Liverani Marco , Ir Por , Wiseman Virginia , Perel Pablo
Published: September 2021

Background

In many low- and middle-income countries (LMICs), health system capacities to address the burden of non-communicable diseases (NCDs) are often inadequate. In these countries, wearable health technologies such as smartbands and smartwatches could be used as part of public health programmes to improve the monitoring, prevention, and control of NCDs. Considering this potential, the purpose of this study was to explore user experiences and perceptions of a health wearable in Cambodia.

Methods

Data collection involved a survey, conducted between November 2019 and January 2020, among different categories of participants (including hypertensive participants, non-hypertensive participants, postgraduate students, and civil servants). All participants were given a sample of a watch-type wearable and advised to use it day and night. One month after product delivery, we conducted a survey to explore their views and experiences. Results were analysed by using descriptive statistics and Chi square or Fisher's exact test to compare responses from urban and rural participants.

Results

A total of 156 adult participants completed the study. Technology acceptance was positive overall. 89.1% of the participants said they would continue using the watch and 76.9% of them would recommend it to either friends or relatives, while 94% said the device stimulated them to think more frequently about their health. However, challenges to technology adoption were also identified, including concerns with the accuracy and quality of the device and unfamiliarity with the concept of health self-monitoring, especially among the elderly. Short battery life and cost were also identified as potential barriers to continued use.

Conclusions

Health wearables are a promising new technology that could be used in Cambodia and in other LMICs to strengthen health sector responses to the challenges of NCDs. However, this technology should be carefully adapted to the local context and the needs of less resourced population groups. In addition, further studies should examine if adequate health sector support and infrastructure are in place to implement and sustain the technology.