bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized trial comparing standard versus thermocontrolled haemodialysis using intradialytic cardiac, brain and renal magnetic resonance imaging
Authors: Gullapudi Venkata R Latha , Cox Eleanor F , Buchanan Charlotte E , Canaud Bernard , White Kelly , Taal Maarten W , Selby Nicholas M , Francis Susan T
Published: July 2023

Background

Ischaemic end-organ damage during haemodialysis (HD) is a significant problem that may be ameliorated by intradialytic cooling. A randomised trial was performed to compare standard HD (SHD; dialysate temperature 37°C) and programmed cooling of the dialysate [thermocontrolled HD (TCHD)] using multiparametric magnetic resonance imaging (MRI) to assess structural, functional and blood flow changes in the heart, brain and kidneys.

Methods

Prevalent HD patients were randomly allocated to receive either SHD or TCHD for 2 weeks before undergoing serial MRI at four time points: pre-, during (30 min and 180 min) and post-dialysis. MRI measures include cardiac index, myocardial strain, longitudinal relaxation time (T1), myocardial perfusion, internal carotid and basilar artery flow, grey matter perfusion and total kidney volume. Participants then crossed to the other modality to repeat the study protocol.

Results

Eleven participants completed the study. Separation in blood temperature between TCHD (−0.1 ± 0.3°C) and SHD (+0.3 ± 0.2°C; P = .022) was observed, although there was no difference in tympanic temperature changes between arms. There were significant intradialytic reductions in cardiac index, cardiac contractility (left ventricular strain), left carotid and basilar artery blood flow velocities, total kidney volume, longitudinal relaxation time (T1) of the renal cortex and transverse relaxation rate (T2*) of the renal cortex and medulla, but no differences between arms. Pre-dialysis T1 of the myocardium and left ventricular wall mass index were lower after 2 weeks of TCHD compared with SHD [1266 ms (interquartile range 1250–1291) versus 1311 ± 58 ms, P = .02; 66 ± 22 g/m2 versus 72 ± 23 g/m2, P = .004].

Conclusions

HD adversely affects cardiac function, reduces carotid and basilar artery blood flow and total kidney volume, but mild dialysate cooling using a biofeedback module did not result in differences in intradialytic MRI measures compared with SHD.
MULTIPLATFORM MOLECULAR ANALYSIS OF VESTIBULAR SCHWANNOMA REVEALS TWO ROBUST SUBGROUPS WITH DISTINCT MICROENVIRONMENT
Authors: Landry Alexander P , Wang Justin Z , Suppiah Suganth , Zadeh Gelareh
Published: July 2023

BTFC travel award recipient

Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle and poses a significant morbidity for patients. While many exhibit benign behaviour, others have a more aggressive nature and pattern of growth. Predicting who will fall into which category consistently remains uncertain. There is a need for a better understanding of the molecular landscape, and important subgroups therein, of this disease.

METHODS: We select all vestibular schwannomas from our tumour bank with both methylation and RNA profiling available. Unsupervised clustering methods were used to define two distinct molecular subgroups of VS which were explored using computational techniques including bulk deconvolution analysis, gene pathway enrichment analysis, and drug repurposing analysis. Methylation data from two other cohorts were used to validate our findings, given a paucity of external samples with available multi-omic data. RESULTS: A total of 75 tumours were analyzed. Consensus clustering and similarity network fusion defined two subgroups ("immunogenic" and "proliferative”) with significant differences in immune, stroma, and tumour cell abundance (p<0.05). Gene network analysis and computational drug repurposing found critical differences in targets of immune checkpoint inhibition PD-1 and CTLA-4, the MEK pathway, and the epithelial to mesenchymal transition program, suggesting a need for subgroup-specific targeted treatment/trial design in the future. CONCLUSIONS: We leverage computational tools with multi-omic molecular data to define two robust subgroups of vestibular schwannoma with differences in microenvironment and therapeutic vulnerabilities.
A FIRST REPORT ON OUTCOMES OF STEREOTACTIC BODY RADIOTHERAPY FOR POSTERIOR ELEMENT ONLY SPINAL METASTASES AND VALIDATION OF RECOMMENDED CLINICAL TARGET VOLUME DELINEATION PRACTICE
Authors: Burgess Laura , Zeng K Liang , Myrehaug Sten , Soliman Hany , Tseng Chia-Lin , Detsky Jay , Chen Hanbo , Palhares Daniel Moore , Witiw Christopher D , Zhang Beibei , Maralani Pejman , Sahgal Arjun
Published: July 2023

Spine stereotactic body radiotherapy (SBRT) improves local control and pain response compared to conventional external beam radiotherapy. Consensus stipulates MRI-based delineation of the clinical target volume (CTV) and is based on spine segment sector involvement. The applicability to metastases limited to the posterior elements remains to be validated. We aimed to determine the patterns of failure and safety of treating posterior element metastases when the vertebral body (VB) was intentionally excluded from the CTV.

METHODS AND MATERIALS: A retrospective review of a prospectively maintained database of 605 patients and 1412 spine segments treated with spine SBRT was performed. Only treated segments involving the posterior elements alone were included. The primary outcome was local failure and secondary outcomes included patterns of failure, toxicities. RESULTS: 24/605 patients and 31/1412 segments were treated to the posterior elements only. Local failure occurred in 11/31 segments. The cumulative rate of local recurrence was 9.7% at 12 months and 30.8% at 24 months. Amongst local failures, the most common histologies were renal cell carcinoma (36.4%) and non-small cell lung cancer (36.4%) and 73% had baseline paraspinal disease extension. 6/11 (54.5%) failed exclusively within treated CTV sectors and 5/11 (45.5%) with both treated and adjacent untreated sectors. 4/5 cases had recurrent disease extending into the VB, but no failure was observed exclusively within the VB. CONCLUSIONS: Posterior element alone metastases are rare. Our analyses support SBRT consensus contouring guidelines such that the VB can be excluded from CTV in spinal metastases confined to the posterior elements.
BEVACIZUMAB FOR SYMPTOMATIC RADIATION NECROSIS IN BRAIN METASTASES: OUTCOMES FROM A SINGLE-CENTER RETROSPECTIVE ANALYSIS
Authors: Roberto Katrina , Tyono Ivan , Soliman Hany , Sahgal Arjun , Perry James , Lim-Fat Mary Jane
Published: July 2023

Radiation necrosis is a late complication after radiotherapy and can be treated with bevacizumab, however predictors of response are not well established. We performed a single-institution retrospective chart review of patients with previously irradiated brain metastases who developed radiation necrosis and were treated with bevacizumab. 19 patients (86% female, median age of 62 years) were included. 50% had metastatic lung cancer, 37% had breast cancer and 11 % had melanoma. 18 had perfusion imaging, 9 had chemical exchange saturation transfer (CEST) imaging to increase diagnostic confidence. 6 cases were tissue-confirmed, 3 before treatment, and 3 upon recurrence after bevacizumab. All patients received a dose of 7.5 mg/kg per infusion every 3 weeks and 63% received 4 infusions. All were symptomatic before treatment. Clinical response was seen in 89% while radiographic response was achieved in 95% of patients. Dexamethasone was successfully discontinued in 71% of steroid-dependent patients. The median duration of response (interval between first infusion and recurrence) was 7.2 months (range: 2.3 to 43.2). Of the nine diagnosed using perfusion and CEST imaging, 89% had clinical response, 100% had a reduction in T2/FLAIR volume and 89% in T1 post-gadolinium enhancement, 83% discontinued dexamethasone. Grade 1/2 adverse events occurred in 8 patients (hypertension, fatigue, rash, joint pain, intracranial hemorrhage). One patient developed a grade 3 bowel perforation requiring surgery. Bevacizumab resulted in significant and prolonged clinical and radiographic improvement in a series of carefully selected patients. CEST imaging helped select responders to bevacizumab in our cohort.
CEREBELLAR DIFFUSE MIDLINE GLIOMA, H3K27M ALTERED IN A FIFTY-FIVE-YEAR-OLD PATIENT
Authors: Ibdah Haleem , Pejhan Shervin , Ang Lee , Hawkins Cynthia , Fisher Barbara , Megyesi Joseph , MacDonald Maria
Published: July 2023

H3 K27M mutations were first identified in Pediatric Diffuse Intrinsic Pontine Glioma and are now recognized in gliomas occurring in other midline locations such as the thalamus, spinal cord and cerebellum. These gliomas were renamed to Diffuse Midline Glioma (DMG) H3 K27-altered in the 2021 WHO classification due to the discovery of alternate mechanisms of H3 K27 loss. These gliomas are more commonly found in children but also occur in adolescents and young adults. We present the case of a 55- year-old woman who presented with a 2.5-month history of nausea, vomiting and gait impairment. Imaging revealed a partially cystic, enhancing lesion in the midline of the cerebellum. She had a gross total resection with pathology revealing Diffuse Midline Glioma, H3K27 altered, subgroup DMG, H3 wildtype with EZHIP over-expression, WHO grade 4. The patient completed chemoradiation with temozolomide with plans to enroll in a clinical trial upon progression. However due to loss of ambulation and function she was admitted to hospice. The patient survived 24 months after her surgery, a period longer than the reported median overall survival in DMG with EZIP overexpression which is 16 months. This case illustrates the importance of considering DMG H3K27- altered glioma in adults older than 40 years who present with infiltrative IDH wildtype glioma in midline locations. Recognition of this diagnosis may allow enrollment in clinical trials and should prompt molecular testing for concurrent targetable alterations in the RAS-MAPK-pathway (e.g., mutations in BRAF V600E, FGFR1, NF1 and NTRK) and PI3K-mTOR pathway (e.g., PIK3CA mutation).
30 GY IN 4 STEREOTACTIC BODY RADIOTHERAPY (SBRT) FRACTIONS FOR COMPLEX SPINAL METASTASES: MATURE OUTCOMES SUPPORTING THIS NOVEL REGIMEN
Authors: Moore-Palhares Daniel , Sahgal Arjun , Liang Zeng K , Myrehaug Sten , Tseng Chia-Lin , Detsky Jay , Chen Hanbo , Ruschin Mark , Atenafu Eshetu G , Wilson Jeff , Larouche Jeremie , da Costa Leodante , Maralani Pejman Jabehdar , Soliman Hany
Published: July 2023

We designed a 30 Gy in 4 fractions stereotactic body radiotherapy (SBRT) protocol, as an alternative option to our standard 2-fraction approach, for primarily large volume, multilevel, or previously radiated spinal metastases. We report imaging-based outcomes of this novel fractionation scheme.

MATERIALS AND METHODS: Retrospective analysis of all patients who underwent 30 Gy/4 fractions from 2010-2021 identified from an institutional database. Primary outcomes were magnetic resonance-based vertebral compression fracture (VCF) and local failure (LF). RESULTS: We reviewed 245 treated segments in 116 patients. The median number of consecutive segments within the treatment volume was 2 (range, 1-6) and clinical target volume (CTV) was 126.2 cc (range, 10.4-863.5). Fifty-four percent had received at least one prior course of radiotherapy. The cumulative incidence of LF was 10.7% (95% CI 7.1-15.2) at 1 year and 16% (95% CI 11.5-21.2) at 2 years. The cumulative incidence of VCF was 7.3% (95% CI 4.4-11.2) at 1 and 11.2% (95% CI 7.5-15.8) at 2 years. On multivariable analysis, age ≥68 years (p=0.038), CTV volume ≥72 cc (p=0.021), and no prior surgery (p=0.021) predicted for VCF. The risk of VCF for CTV volumes <72 cc/≥72 cc was 1.8%/14.6% at 2 years. No case of radiation-induced myelopathy was observed. CONCLUSION: 30 Gy in 4 fractions was safe and efficacious despite a population at increased risk of toxicity. The lower risk of VCF in previously stabilized segments highlights the potential for a multi-modal treatment approach for complex metastases, especially for those with CTV volume ≥72 cc.
What, where, and how: Regulation of translation and the translational landscape in plants
Authors: Wu Hsin-Yen Larry , Jen Joey , Hsu Polly Yingshan
Published: July 2023

Translation is a crucial step in gene expression and plays a vital role in regulating various aspects of plant development and environmental responses. It is a dynamic and complex program that involves interactions between mRNAs, transfer RNAs, and the ribosome machinery through both cis- and trans-regulation while integrating internal and external signals. Translational control can act in a global (transcriptome-wide) or mRNA-specific manner. Recent advances in genome-wide techniques, particularly ribosome profiling and proteomics, have led to numerous exciting discoveries in both global and mRNA-specific translation. In this review, we aim to provide a “primer” that introduces readers to this fascinating yet complex cellular process and provide a big picture of how essential components connect within the network. We begin with an overview of mRNA translation, followed by a discussion of the experimental approaches and recent findings in the field, focusing on unannotated translation events and translational control through cis-regulatory elements on mRNAs and trans-acting factors, as well as signaling networks through 3 conserved translational regulators TOR, SnRK1, and GCN2. Finally, we briefly touch on the spatial regulation of mRNAs in translational control. Here, we focus on cytosolic mRNAs; translation in organelles and viruses is not covered in this review.
Multifidus dysfunction and restorative neurostimulation: a scoping review
Authors: Tieppo Francio Vinicius , Westerhaus Benjamin D , Carayannopoulos Alexios G , Sayed Dawood
Published: July 2023

Objective

Chronic low back pain (CLBP) is multifactorial in nature, with recent research highlighting the role of multifidus dysfunction in a subset of nonspecific CLBP. This review aimed to provide a foundational reference that elucidates the pathophysiological cascade of multifidus dysfunction, how it contrasts with other CLBP etiologies and the role of restorative neurostimulation.

Methods

A scoping review of the literature.

Results

In total, 194 articles were included, and findings were presented to highlight emerging principles related to multifidus dysfunction and restorative neurostimulation. Multifidus dysfunction is diagnosed by a history of mechanical, axial, nociceptive CLBP and exam demonstrating functional lumbar instability, which differs from other structural etiologies. Diagnostic images may be used to grade multifidus atrophy and assess other structural pathologies. While various treatments exist for CLBP, restorative neurostimulation distinguishes itself from traditional neurostimulation in a way that treats a different etiology, targets a different anatomical site, and has a distinctive mechanism of action.

Conclusions

Multifidus dysfunction has been proposed to result from loss of neuromuscular control, which may manifest clinically as muscle inhibition resulting in altered movement patterns. Over time, this cycle may result in potential atrophy, degeneration and CLBP. Restorative neurostimulation, a novel implantable neurostimulator system, stimulates the efferent lumbar medial branch nerve to elicit repetitive multifidus contractions. This intervention aims to interrupt the cycle of dysfunction and normalize multifidus activity incrementally, potentially restoring neuromuscular control. Restorative neurostimulation has been shown to reduce pain and disability in CLBP, improve quality of life and reduce health care expenditures.
Glucocorticoid treatment in SLE is associated with infections, comorbidities and mortality—a national cohort study
Authors: Frodlund Martina , Jönsen Andreas , Remkus Lauren , Telg Gunilla , Söderdahl Fabian , Leonard Dag
Published: July 2023

Objectives

Patients with SLE have an increased risk of comorbidities and impaired survival. We aimed to assess whether various thresholds of oral CS (OCS) can predict development of infections, comorbidities, malignancies and survival in SLE using data from national health registries in Sweden.

Methods

All incident SLE cases, age >18 years, in Sweden (n = 5309) between 2005 and 2020 and matched population controls (n = 26 545) were included and followed until 2020, a total of 257 942 patient years. Data from national registers were retrieved including information from the National Prescribed Drug Register. Risk factors were analysed using time-dependent Cox regression models.

Results

Compared with no OCS, >0 to <5.0 mg/day, 5.0–7.5 mg/day as well as >7.5 mg/day OCS predicted development of infections (pneumonia, influenza, herpes zoster and urinary tract infection), osteoporosis, osteonecrosis, gastroduodenal ulcers, cataracts, hypertension and mortality (all P < 0.05). OCS >0 to <5.0 mg/day was associated with lower hazard ratios for these comorbidities than higher doses of OCS. Fifteen years after diagnosis, 48% of patients were taking OCS at a median dose of 5.7 mg/day. A small reduction of OCS treatment 5 years after diagnosis in patients diagnosed with SLE 2006–10 compared with 2011–15 was observed, 49% vs 46% respectively (P = 0.039).

Conclusion

Results highlight the potential harm associated with even low OCS dose treatment in SLE and the need to judiciously use OCS at the lowest possible dose to maximize efficacy and minimize harm.
Assessing comfort with sexuality-related questions in medical students: “a little discomfort is better than a lifetime of suffering in silence”
Authors: Thomson Jantien , Ross Michael W , van Deventer Heidi , Poelsma Mieke , Pienaar Marie E , du Toit Marlena , Botha Matthys H
Published: July 2023

Background

Sexual history–taking competence in medical students is an essential skill that they need to acquire. It requires them to learn to develop comfort in using sexuality-related language and raising the subject with patients. Sexual history exploration skills are inadequately taught in a significant number of medical schools.

Aim

We studied comfort levels in using sexuality-related language in medical students who had no training yet in history taking.

Methods

First-year medical students in a South African university engaged in an exercise in pairs—a dyad—alternating the role of interviewer and interviewee. Provided questions and answers were offered to the students, who videotaped their dyad interview and uploaded it to a safe university environment for peer review.

Outcomes

As part of the exercise, students rated their comfort in the interview for 35 questions on a 5-point Likert scale. Students then participated in online discussion forums with fellow students and tutors on their experience.

Results

Students posing the questions, the interviewers, were significantly more comfortable with the questions than interviewees. Total comfort scores over the 35 questions showed a roughly normal distribution for both. Questions with explicit sexual behavior or vocabulary were rated more uncomfortable by interviewers as well as interviewees. The total scores for interviewers showed a distribution with a longer tail toward discomfort. Female interviewees were significantly more uncomfortable than male interviewees, but this was not the case for interviewers. Dyads of 2 females were significantly more uncomfortable than mixed-gender and 2-male dyads. Qualitative data showed wide acceptance of the exercise by students, with increasing confidence and comfort in using sexually explicit terms in strong appreciation of the responder’s perspective in the exercise, as well as awareness that receiving a question—the patient’s position—is more uncomfortable.

Clinical Translation

Data indicate that comfort assessment in asking sexuality-related questions with expected different levels of comfort and discomfort is a valuable measure that can evaluate progress in this skill. The data also suggest the need for students to select profiles and questions to provide a trauma-informed approach, knowing that some of the medical students will have experienced sexually related trauma, as in the general population.

Strengths and Limitations

This study provides a method and student feedback in teaching sexual history elicitation and increasing comfort with sexual language in a clinical context. The study is limited to first-year medical students.

Conclusion

Histories with provided questions and answers allow for rating of comfort and provision of trauma-informed education in developing sexual history exploration clinical skills.
Human-relevant exposure to di-n-butyl phthalate tampers with the ovarian insulin-like growth factor 1 system and disrupts folliculogenesis in young adult mice
Authors: Jauregui Estela J , McSwain Maile , Liu Xiaosong , Miller Kara , Burns Kimberlie , Craig Zelieann R
Published: July 2023

Phthalates are compounds used in consumer and medical products worldwide. Phthalate exposure in women has been demonstrated by detection of phthalate metabolites in their urine and ovarian follicular fluid. High urinary phthalate burden has been associated with reduced ovarian reserve and oocyte retrieval in women undergoing assisted reproduction. Unfortunately, no mechanistic explanation for these associations is available. In short term in vivo and in vitro animal studies modeling human-relevant exposures to di-n-butyl phthalate (DBP), we have identified ovarian folliculogenesis as a target for phthalate exposures. In the present study, we investigated whether DBP exposure negatively influences insulin-like growth factor 1 (IGF1) signaling in the ovary and disrupts ovarian folliculogenesis. CD-1 female mice were exposed to corn oil (vehicle) or DBP (10 µg/kg/day, 100 µg/kg/day, or 1000 mg/kg/day) for 20–32 days. Ovaries were collected as animals reached the proestrus stage to achieve estrous cycle synchronization. Levels of mRNAs encoding IGF1 and 2 (Igf1 and Igf2), IGF1 receptor (Igf1r), and IGF-binding proteins 1–6 (Ifgbp1–6) were measured in whole ovary homogenates. Ovarian follicle counts and immunostaining for phosphorylated IGF1R protein (pIGF1R) were used to evaluate folliculogenesis and IGF1R activation, respectively. DBP exposure, at a realistic dose that some women may experience (100 µg/kg/day for 20–32 days), reduced ovarian Igf1 and Igf1r mRNA expression and reduced small ovarian follicle numbers and primary follicle pIGF1R positivity in DBP-treated mice. These findings reveal that DBP tampers with the ovarian IGF1 system and provide molecular insight into how phthalates could influence the ovarian reserve in females.
Health Status of Ready-to-Plant Grapevine Nursery Material in Canada Regarding Young Vine Decline Fungi
Authors: Hrycan Jared , Theilmann Jane , Mahovlic April , Boulé Julie , Úrbez-Torres José Ramón
Published: July 2023

Young vine decline (YVD), caused by several taxonomically different fungi, results in the decline and death of grapevines within a few years after planting. Infection can occur in nursery mother blocks and/or at several stages in the nursery propagation process, but the final plant material may remain asymptomatic. Four nurseries that sell ready-to-plant grapevines in Canada were sampled to evaluate the health status with regard to YVD fungi, including Botryosphaeriaceae spp., Cadophora luteo-olivacea, Dactylonectria macrodidyma, Dactylonectria torresensis, Phaeoacremonium minimum, and Phaeomoniella chlamydospora. Plants representing three cultivars, ‘Chardonnay’, ‘Merlot’, and ‘Pinot noir’, either grafted onto ‘3309C’ rootstock or self-rooted, were provided by the nurseries. Samples from the roots, base of the rootstock or self-rooted cultivar, graft-union, and scion were collected from each plant. DNA was extracted, and the total abundance of each fungus was quantified using Droplet Digital PCR. Results revealed that 99% of plants harbored at least one of the fungi studied, with a mean of three different fungal species that were present per grapevine. Droplet Digital PCR results showed that the abundance of the different fungi significantly varied between different sections of each plant, individual plants for each cultivar, and cultivars from the same nursery. Necrosis measurements were recorded from the base of the rootstock or self-rooted cultivars and did not correlate with fungal abundance recorded in that section for each grapevine, but necrosis was consistent across cultivars within nurseries. Five different rootstocks were compared from one nursery, and results showed no differences between rootstocks and their health status. Among all nurseries, C. luteo-olivacea was the most prevalent fungus (97% of the plants), while D. macrodidyma was the least commonly found (13% of the plants). This study shows that ready-to-plant nursery material sold in Canada is likely to be infected with several YVD fungi and that presence and abundance of fungi vary significantly among individual grapevines and nurseries.
Micheliolide exerts effects in myeloproliferative neoplasms through inhibiting STAT3/5 phosphorylation via covalent binding to STAT3/5 proteins
Authors: Huang Huijun , Liu Jinqin , Yang Lin , Yan Yiru , Chen Meng , Li Bing , Xu Zefeng , Qin Tiejun , Qu Shiqiang , Wang Liang , Huang Gang , Chen Yue , Xiao Zhijian
Published: July 2023

Ruxolitinib is a cornerstone of management for some subsets of myeloproliferative neoplasms (MPNs); however, a considerable number of patients respond suboptimally. Here, we evaluated the efficacy of micheliolide (MCL), a natural guaianolide sesquiterpene lactone, alone or in combination with ruxolitinib in samples from patients with MPNs, JAK2V617F-mutated MPN cell lines, and a Jak2V617F knock-in mouse model. MCL effectively suppressed colony formation of hematopoietic progenitors in samples from patients with MPNs and inhibited cell growth and survival of MPN cell lines in vitro. Co-treatment with MCL and ruxolitinib resulted in greater inhibitory effects compared with treatment with ruxolitinib alone. Moreover, dimethylaminomicheliolide (DMAMCL), an orally available derivative of MCL, significantly increased the efficacy of ruxolitinib in reducing splenomegaly and cytokine production in Jak2V617F knock-in mice without evident effects on normal hematopoiesis. Importantly, MCL could target the Jak2V617F clone and reduce mutant allele burden in vivo. Mechanistically, MCL can form a stable covalent bond with cysteine residues of STAT3/5 to suppress their phosphorylation, thus inhibiting JAK/STAT signaling. Overall, these findings suggest that MCL is a promising drug in combination with ruxolitinib in the setting of suboptimal response to ruxolitinib.
Durability of Functional Outcomes After MRI-Guided Transurethral Ultrasound Ablation of the Prostate
Authors: Hatiboglu Gencay , Nair Shiva , Relle James , Hafron Jason , Kassam Zahra , Nandalur Kiran , Mueller-Wolf Maya , Bonekamp David , Doerwald Pouya , Clarke Gina M. , Schlemmer Heinz-Peter , Roethke Matthias , Pahernik Sascha , Chin Joseph
Published: July 2023

Long-term data on functional outcomes after MRI-guided transurethral ultrasound ablation (TULSA) are limited. We assess the 5-year post-TULSA durability of outcomes for patient-reported genitourinary function, bowel function, and adverse events in 30 patients with primary, localized prostate cancer treated with TULSA across 3 centers. Patients received a conservative treatment plan in a phase 1 study designed to assess safety and feasibility. Follow-up visits took place at 1, 3, 6, 12 months, and biannually up to 5 years. Median (interquartile range) age at baseline was 69 (67-71) years. Erectile dysfunction (International Index of Erectile Function [IIEF] ≤17) was prevalent at baseline, with a mean (95% confidence interval [CI]) score of 16 (12-19), decreasing to 9 (4-14) at 5 years. At the 5-year visit, 71% of men who attempted intercourse in the recall period reported preservation of IIEF Q2 ≥2 erections sufficient for penetration. The mean (95% CI) International Prostate Symptom Score (IPSS) decreased from 9.0 (7.0-11) to 7.1 (5.0-9.1) from baseline to 5 years; IPSS-quality of life, maximum urinary flow rate, and post-void residual urine were stable or improved. Maintenance of bowel function and urinary continence was 100%. There was no new attributable serious or severe adverse event from 1 to 5 years. With a durably favorable safety profile, TULSA has the potential to treat cancer conservatively while simultaneously alleviating lower urinary tract symptoms. Data from larger studies are pending.
Relationship Between Adherent Perinephric Fat and Sex Hormone Levels in Serum and Fat in Patients Undergoing Robotic-Assisted Partial Nephrectomy: A Prospective Study
Authors: Miyazawa Yoshiyuki , Nomura Masashi , Matsumura Nozomi , Fujizuka Yuji , Sekine Yoshitaka , Tsuji Yusuke , Syuto Takahiro , Yokoo Hideaki , Suzuki Kazuhiro
Published: July 2023

Background:

Perinephric fat removal is essential for safe and effective robotic-assisted partial nephrectomy (RAPN). Adherent perinephric fat (APF) occasionally compromises RAPN, but the relationship between such fat and sex hormone levels is unclear. We explored a possible association between APF and sex hormone levels in serum and APF tissue.

Patients and Methods:

We conducted a prospective study from 2021 to 2022 at Gunma University Hospital. Fifty patients treated using RAPN were analyzed. We measured the testosterone (T) and estradiol (E) levels in serum and perinephric fat using liquid chromatography-mass spectrometry (LC-MS/MS). The correlations between the extent of adherence measured intraoperatively and hormone concentrations were examined.

Results:

Of the 50 cases, 36 were male, and 14 were female. APF was observed in 16 of the male patients but in no female patients. In male patients, the T levels in perinephric fat were significantly higher in patients with APF. E2 levels in perinephric fat tissue were also significantly higher in patients with APF.

Conclusion:

In the 36 male patients lacking APF, there were no significant differences in the serum levels of T compared with those with APF, but a significant difference was apparent in APF tissue. The changed T level in APF tissue may have affected APF development.
Body Composition and Physical Activity in Pediatric Intestinal Failure On and Off Parenteral Nutrition
Authors: Yanchis Dianna , So Stephanie , Patterson Catherine , Belza Christina , Garofalo Elizabeth , Wong-Sterling Sylvia , Silva Carina , Avitzur Yaron , Wales Paul W. , Hulst Jessie M. , Kong Dehan , Xu Libai , Li Yuxuan , Courtney-Martin Glenda
Published: July 2023

Objectives:

Data on the relationship between body composition (BC) and physical activity (PA) in children with intestinal failure (IF) are lacking. The objectives were to collect data on PA and BC in children with IF, both parenterally and enterally fed, and to assess the relationship between PA and BC.

Methods:

Cross-sectional study in children 5–18 years with IF including those receiving parenteral nutrition (PN) and those fully enterally fed. PA levels were measured using accelerometry. BC was measured by dual-energy X-ray absorptiometry. Data were compared to age- and sex-matched population norms using t tests. Regression analysis assessed the relationship between BC and PA.

Results:

Fifty-eight children with IF (38 males), mean (SD) age of 10.0 (3.5) years, 20 dependent on PN were included. Patients with IF had significantly fewer steps per day (P ≤ 0.001) compared with literature controls, with a mean (SD) of 7,972 (3,008) and 11,749 (1,106), respectively. There were no significant differences between patients receiving PN and those enterally fed, but both groups were significantly less active than literature controls (P < 0.001). Patients with IF had higher fat mass and lower fat-free mass compared to literature controls (P = 0.008). PA had a significant effect on BC (r
2 = 0.32, P < 0.001).

Conclusions:

Children with IF, those receiving PN and those fully enterally fed, are at risk of decreased PA and altered BC. PA should be part of ongoing rehabilitation and management to optimize outcomes.
The mechanical failure of locally manufactured prosthetic feet from the Jaffna Jaipur Centre for Disability Rehabilitation (JJCDR), Sri Lanka
Authors: Ranson Gemma , Morley Matthew , Corsial Nathan , Sathiadas Gitanjali , Ganeshamoorthy Jeya , Berthaume Michael
Published: July 2023

Background:

The International Organization for Standardization (ISO) 10328 standards are used to verify the safety of lower limb prosthetic devices. However, the ISO 10328 tests are performed in sterile laboratory settings and do not account for environmental or sociocultural factors associated with prosthetic use. Most locally manufactured prosthetic feet from low-income and middle-income countries, which are safely used for years, do not meet these standards. In this study, we investigate the modes of wear patterns of naturally worn prosthetic feet from Sri Lanka.

Objective:

To characterize wear patterns of locally manufactured prosthetic feet from low-income and middle-income countries.

Methods:

Sixty-six replaced prosthetic feet from the Jaffna Jaipur Center of Disability and Rehabilitation were analyzed. Delamination between the keel and rest of the foot could not be detected with ultrasound. Sole wear pattern was quantified by photographing soles and dividing them into 200 rectangles and scoring the rectangle’s wear from 1 to 9 (no to extreme wear). Homologous scores were averaged to create a contour map of prosthetic foot wear.

Results:

The highest levels of wear occurred at the heel, end of the keel, and the perimeter of the prosthetic foot. All regions of the prosthetic feet had significantly different wear scores (p < 0.005).

Conclusions:

Locally manufactured solid ankle cushion heel feet display high levels of wear in localized areas of the sole of prosthetic feet, which can limit their life span. High levels of wear occur at the end of the keel, which would not be detectable in the ISO 10328 tests.
Challenges in the management of depressive disorders comorbid with tuberculosis and type 2 diabetes
Authors: Caceres-Cardenas Guillermo , Ruiz-Grosso Paulo , Ugarte-Gil Cesar
Published: July 2023

Purpose of review

The aim of this study was to address the most relevant diagnostic and therapeutic challenges in the management of depressive disorders among patients with diabetes mellitus and tuberculosis (TB).

Recent findings

Depressive disorder, diabetes mellitus and TB are considered important contributors to the global burden of diseases with an emphasis on developing countries. Depressive disorder increases the chance of negative outcomes during the treatment of both diabetes mellitus and TB, while biological and adaptive changes due to diabetes mellitus and TB increase in turn the chance of depressive disorder.

In this review, we present major challenges in the management of depressive disorder among patients with TB and diabetes mellitus, from detection and clinical diagnosis using appropriate diagnostic tools, to selecting the best psychotherapeutic and/or pharmacological intervention, considering the potential, adverse events and interactions due to potential polypharmacy.
Ethical dilemmas of mental healthcare for migrants and refugees
Authors: Schouler-Ocak Meryam , Iris T. Graef-Calliess
Published: July 2023

Purpose of review

This review will discuss the current development of ethical dilemmas in psychiatry in the care of migrants and refugees. The world is in times of increasing conflicts and disasters, which are leading to increased migration and flight. In dealing with patients, psychiatrists have their own codes of ethics. The purpose of developing codes of ethics is to serve educational and regulatory functions and to provide explicit and visible standards for the professional conduct of psychiatrists.

Recent findings

The codes of ethics are more recognised and required as standards in the form of guiding ethical principles on duties and rights as well as explicit rules. However, in the case of migrants and refugees, ethical principles are suspended in many places, exposing patients to different barriers.

Many National Psychiatric Associations have adopted the World Psychiatric Association or European Psychiatric Association Code of Ethics for Psychiatry. However, migrants and refugees still do not have the same rights and opportunities to access mental healthcare as well as preventive measures and thus equal treatment due to various barriers. Not only is equal treatment suspended in comparison to native patients, but also access to care between migrants and refugees from different regions of origin for various reasons. This invalidates the ethical principles.
Is suicide a mental health, public health or societal problem?
Authors: Goel Digvijay , Dennis Brian , McKenzie Sarah K.
Published: July 2023

Purpose of review

Suicide is a complex phenomenon wherein multiple parameters intersect: psychological, medical, moral, religious, social, economic and political. Over the decades, however, it has been increasingly and almost exclusively come to be viewed through a biomedical prism. Colonized thus by health and more specifically mental health professionals, alternative and complimentary approaches have been excluded from the discourse. The review questions many basic premises, which have been taken as given in this context, particularly the ‘90 percent statistic’ derived from methodologically flawed psychological autopsy studies.

Recent findings

An alternative perspective posits that suicide is a societal problem which has been expropriated by health professionals, with little to show for the efficacy of public health interventions such as national suicide prevention plans, which continue to be ritually rolled out despite a consistent record of repeated failures. This view is supported by macro-level data from studies across national borders.

The current framing of suicide as a public health and mental health problem, amenable to biomedical interventions has stifled seminal discourse on the subject. We need to jettison this tunnel vision and move on to a more inclusive approach.
Bordetella trematum bacteraemia secondary to an empyema in an immunocompromised host: A case report and review of the literature
Authors: Wong Crystal , Calungsud Lynna Grace , La My-Van
Published: July 2023

Introduction.

Bordetella trematum

infection remains uncommon. More cases of bacteraemia are reported in recent years with the primary infection largely originating from skin and soft tissue sites. Yet, our understanding of its virulence, antibiotic susceptibility profile and treatment is still limited.

Case presentation. We report the first case of

B. trematum

bacteraemia from a left-sided empyema. An 87-year-old female patient with a past medical history of ischaemic heart disease, diabetes mellitus complicated by nephropathy and locally advanced left breast adenocarcinoma presented with fever, productive cough and shortness of breath. The

B. trematum

isolates from blood and pleural fluid were identified by MALDI-TOF and 16S rRNA sequencing. Ceftriaxone and azithromycin commenced empirically on admission were switched to piperacillin-tazobactam after 2 days due to lack of clinical improvement. Despite a pleurocentesis and 1 week of piperacillin-tazobactam with microbiological clearance in blood, the patient continued to deteriorate. Decision to withdraw treatment was made in view of the patient’s prognosis, and the patient succumbed on the fourteenth day of admission. The isolate was susceptible to piperacillin-tazobactam, imipenem and meropenem but had reduced susceptibility or was non-susceptible to cefuroxime, cefotaxime, ceftazidime, cefepime, the aminoglycosides and fluoroquinolones.

Conclusion. Invasive

B. trematum

infection is associated with significant mortality. Consensus for antibiotic treatment remains unclear, with limited susceptibility data to support specific antibiotic use. We expect more clinical cases will surface with improved microbial identification systems, as well as enhanced clinical awareness. Standardized and more robust susceptibility work are needed to provide clear recommendations and establish consensus in treating invasive infections.
Description of Salinimicrobium tongyeongense sp. nov., isolated from seawater
Authors: Ganbat Dariimaa , Lee Dong-Woo , Kim Seong-Bo , Lee Yong-Jik , Nam Gaewon , Chi Won-Jae , Lee Byoung-Hee , Jung You-Jung , Lee Jung-Sook , Lee Sang-Jae
Published: July 2023

A Gram-stain-negative, non-motile by gliding and moderately halophilic rod-shaped bacterium HN-2-9-2T was isolated from seawater in Tongyeong, Republic of Korea. The strain grew at concentrations of 0.5‒7 % (w/v) NaCl, at pH 5.5‒8.5 and in a temperature range of 18‒45 °C. HN-2-9-2T shared the highest 16S rRNA gene sequence percentage with

Salinimicrobium xinjiangense

BH206T (98.2 %). The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA–DNA hybridisation (dDDH) values between HN-2-9-2T and the

S. xinjiangense

BH206T were 76.0 %, 81.9 % and 19.7 %, respectively. The genome comprised 3 509 958 bp with a DNA G+C content of 43.0%. HN-2-9-2T contained MK-6 as the sole menaquinone. The predominant fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C17 : 0 3-OH, iso-C16 : 0, iso-C15 : 1G and summed feature 9, comprising iso-C17 : 1ω6c/C16 : 1 10-methyl. The polar lipids contained phosphatidylethanolamine, one unidentified phospholipid, two unidentified aminolipids, an unidentified glycolipid and six unidentified lipids. The polyphasic taxonomic properties indicate that the strain represents a novel species within the genus

Salinimicrobium

, for which the name Salinimicrobium tongyeongense sp. nov. is proposed. The type strain is HN-2-9-2T (=KCTC 82934T=NBRC 115920T).
The gut microbiome and resistome of conventionally vs. pasture-raised pigs
Authors: Holman Devin B. , Gzyl Katherine E. , Kommadath Arun
Published: July 2023

Conventional swine production typically houses pigs indoors and in large groups, whereas pasture-raised pigs are reared outdoors at lower stocking densities. Antimicrobial use also differs, with conventionally raised pigs often being exposed to antimicrobials directly or indirectly to control and prevent infectious disease. However, antimicrobial use can be associated with the development and persistence of antimicrobial resistance. In this study, we used shotgun metagenomic sequencing to compare the gut microbiomes and resistomes of pigs raised indoors on a conventional farm with those raised outdoors on pasture. The microbial compositions as well as the resistomes of both groups of pigs were significantly different from each other. Bacterial species such as

Intestinibaculum porci

,

Pseudoscardovia radai

and

Sharpea azabuensis

were relatively more abundant in the gut microbiomes of pasture-raised pigs and Hallella faecis and

Limosilactobacillus reuteri

in the conventionally raised swine. The abundance of antimicrobial resistance genes (ARGs) was significantly higher in the conventionally raised pigs for nearly all antimicrobial classes, including aminoglycosides, beta-lactams, macrolides-lincosamides-streptogramin B, and tetracyclines. Functionally, the gut microbiomes of the two group of pigs also differed significantly based on their carbohydrate-active enzyme (CAZyme) profiles, with certain CAZyme families associated with host mucin degradation enriched in the conventional pig microbiomes. We also recovered 1043 dereplicated strain-level metagenome-assembled genomes (≥90 % completeness and <5 % contamination) to provide taxonomic context for specific ARGs and metabolic functions. Overall, the study provides insights into the differences between the gut microbiomes and resistomes of pigs raised under two very different production systems.
Modulation of Neural Networks and Symptom Correlated in Fibromyalgia: A Randomized Double-blind Factorial Explanatory Clinical Trial of Home-Based Transcranial Direct Current Stimulation
Authors: Lopes Alves Rael , Zortea Maxciel , Vicuña Serrano Paul , dos Santos Laranjeira Vani , Franceschini Tocchetto Betina , Ramalho Leticia , Fernanda da Silveira Alves Camila , Brugnera Tomedi Rafaela , Pereira de Almeida Rodrigo , Machado Bruck Samara , Medeiros Liciane , Sanches Paulo R. S. , Silva Danton P. , Lucena da Silva Torres Iraci , Fregni Felipe , Caumo Wolnei
Published: July 2023

Transcranial direct current stimulation (tDCS) might modulate neural activity and promote neural plasticity. This factorial randomized clinical trial compared a-tDCS on the left dorsolateral prefrontal cortex (l-DLPFC) or sham (s-tDCS), and a-tDCS or s-tDCS on the primary motor cortex (M1) in the connectivity analyses in eight regions of interest (ROIs) across eight resting-state electroencephalography (EEG) frequencies. We included 48 women with fibromyalgia, aged 30 to 65, randomly assigned to 2:1:2:1 to receive 20 sessions during 20 minutes of a-tDCS 2mA or s-tDCS at home, over l-DLPFC or M1, respectively. EEG recordings were obtained before and after treatment with eyes open (EO) and eyes closed (EC). In the EC condition, comparing pre to post-treatment, the a-tDCS on l-DLPFC decreased the lagged coherence connectivity in the delta frequency band between the right insula and left anterior cingulate cortex (ACC) (t=-3.542, p=.048). The l-DLPFC a-tDCS compared to s-tDCS decreased the lagged coherence connectivity in the delta frequency band between the right insula and left ACC (t=-4.000, p=.017). In the EO condition, the l-DLPFC a-tDCS compared to M1 s-tDCS increased the lagged coherence connectivity between the l-DLPFC and left ACC in the theta band (t=-4.059, p=.048). Regression analysis demonstrated that the a-tDCS effect on the l-DLPFC was positively correlated with sleep quality, while a-tDCS on l-DLPFC and M1 s-tDCS were positively correlated with pain catastrophizing. The application of a-tDCS over the l-DLPFC has modulated the connectivity between various brain regions involved in the affective-attentional aspects of pain, especially at lower EEG frequencies during the resting state. These findings suggest that the effects of a-tDCS on neural oscillations could serve as a neural marker associated with its impact on fibromyalgia symptoms.
Neural Correlates of Perceptual Similarity Masking in Primate V1
Authors: Chen Spencer C. , Chen Yuzhi , Geisler Wilson S. , Seidemann Eyal
Published: July 2023

Visual detection is a fundamental natural task. Detection becomes more challenging as the similarity between the target and the background in which it is embedded increases, a phenomenon termed “similarity masking”. To test the hypothesis that V1 contributes to similarity masking, we used voltage sensitive dye imaging (VSDI) to measure V1 population responses while macaque monkeys performed a detection task under varying levels of target-background similarity. Paradoxically, we find that during an initial transient phase, V1 responses to the target are enhanced, rather than suppressed, by target-background similarity. This effect reverses in the second phase of the response, so that in this phase V1 signals are positively correlated with the behavioral effect of similarity. Finally, we show that a simple model with delayed divisive normalization can qualitatively account for our findings. Overall, our results support the hypothesis that a nonlinear gain control mechanism in V1 contributes to perceptual similarity masking.