bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse pregnancy outcomes and future risk of heart failure
Authors: Pabón Maria A. , Misra Amrit , Honigberg Michael C.
Published: March 2023

Purpose of review

Cardiovascular disease (CVD) is the leading cause of death in women. Women with history of adverse pregnancy outcomes (APOs) have approximately two-fold risk of future CVD, but until recently the association with future heart failure (HF) was unclear. Here, we summarize evidence for associations of APOs with HF, potential underlying mechanisms, and future directions for clinical translation.

Recent findings

Women with history of hypertensive disorders of pregnancy (HDPs) have roughly two-fold risk of future HF compared with other parous women even after accounting for interval development of coronary artery disease. The HDPs portend heightened risk of HF with both reduced and preserved ejection fraction. Gestational diabetes mellitus (GDM) and other APOs such as preterm delivery, small-for-gestational-age delivery, and placental abruption may also confer additional risk for HF development. Possible underlying mechanisms linking APOs to HF include shared upstream risk factors and genetics, accelerated development of cardiometabolic risk factors postpartum, persistent endothelial and microvascular dysfunction, and impaired natriuretic peptide signaling.

History of APOs, including HDPs and GDM, confer increased risk for development of HF years after delivery. Further research is needed to define strategies to optimize prepregnancy and postpartum cardiovascular health toward HF prevention.
The role of skeletal muscle mass on cardiovascular disease risk: an emerging role on modulating lipid profile
Authors: Damigou Evangelia , Kouvari Matina , Panagiotakos Demosthenes
Published: March 2023

Purpose of review

The purpose of this review was to present updated evidence on the role of skeletal muscle mass on cardiometabolic health.

Recent findings

Increased lean, and especially skeletal, muscle mass has been associated with better cardiometabolic health in various epidemiological studies, even in younger age groups. In addition, the link between skeletal muscle mass and adult lipid profile is of interest. A preliminary analysis using the data from the ATTICA prospective cohort study (2002–2022) supports this association.

Skeletal muscle mass has many metabolic functions (i.e., glucose, insulin and protein metabolism, mitochondrial function, arterial stiffness, inflammation, oxidative stress, brain function, hormone status). Given its associations with the lipid profile and overall cardiometabolic risk, skeletal muscle mass stands among the emerging risk factors for cardiovascular diseases. In addition to only using body mass index or fat distribution, more studies should evaluate lean mass and its prognostic and predictive ability regarding chronic diseases.
Dermatoscopy and Optical Coherence Tomography in Vulvar High-Grade Squamous Intraepithelial Lesions and Lichen Sclerosus: A Prospective Observational Trial
Authors: Huisman Bertine W. , Pagan Lisa , Naafs Rosanne G.C. , ten Voorde Wouter , Rissmann Robert , Piek Jurgen M.J. , Damman Jeffrey , Juachon Maria J. , Osse Michelle , Niemeyer-van der Kolk Tessa , van Hees Colette L.M. , van Poelgeest Mariette I.E.
Published: March 2023

Objective

This study aimed to examine potential discriminatory characteristics of dermatoscopy and dynamic optical coherence tomography (D-OCT) on vulvar high-grade squamous intraepithelial lesions (vHSIL) and lichen sclerosus (LS) compared with healthy vulvar skin.

Methods

A prospective observational clinical trial was performed in 10 healthy volunteers, 5 vHSIL and 10 LS patients. Noninvasive imaging measurements using dermatoscopy and D-OCT were obtained at several time points, including lesional and nonlesional vulvar skin. Morphologic features of vHSIL and LS were compared with healthy controls. Epidermal thickness and blood flow were determined using D-OCT. Patients reported tolerability of each study procedure, including reference vulvar biopsies. The main outcome measures were feasibility and tolerability of imaging modalities, dermatoscopy and OCT characteristics, OCT epidermal thickness and D-OCT dermal blood flow.

Results

The application of dermatoscopy and D-OCT is feasible and tolerable. In vHSIL, dermatoscopic warty structures were present. In LS, sclerotic areas and arborizing vessels were observed. Structural OCT in the vulvar area aligned with histology for hyperkeratosis and dermal-epidermal junction visualization. Currently, the OCT algorithm is unable to calculate the epidermal thickness of the uneven vulvar area. Dynamic optical coherence tomography showed statistically significant increased blood flow in LS patients (mean ± SD, 0.053 ± 0.029) to healthy controls (0.040 ± 0.012; p = .0024).

Conclusions

The application of dermatoscopy and D-OCT is feasible and tolerable in vHSIL and LS patients. Using dermatoscopy and D-OCT, we describe potential characteristics to aid differentiation of diseased from healthy vulvar skin, which could complement clinical assessments.
Inclisiran: present and future perspectives of a new effective LDL cholesterol-lowering agent
Authors: Giordano Salvatore , Polimeni Alberto , Esposito Giovanni , Indolfi Ciro , Spaccarotella Carmen
Published: March 2023

Purpose of review

To highlight critical aspects of inclisiran, from preclinical studies to current recommendations in clinical practice and future perspectives.

Recent findings

Inclisiran use has been recently approved by regulatory agencies. The evidence of its efficacy and safety makes it a promising therapeutical tool for treating dyslipidemias.

The link between LDL-cholesterol and atherosclerotic cardiovascular disease (ASCVD) is well established. Inclisiran, a small interfering RNA, has proven its safety and efficacy in reducing LDL-cholesterol, and FDA and EMA have recently approved its use. This review illustrates the development, structure, and mechanism of action of inclisiran and provides information regarding its efficacy, safety, and current recommendation in clinical practice. Moreover, it provides key information on the most recent/ongoing trials that will help us to implement the use of inclisiran in clinical practice.
Second Opinions for Patients With a Persistent Depressive Disorder: Effects on Severity of Depression and Quality of Life
Authors: de Vocht Anneke M.R. , Witteman Cillia L.M. , de Vocht Frank , Spijker Jan
Published: March 2023

Background:

A persistent depressive disorder has a major impact on both patients and health care systems. Despite the advice in guidelines to seek a second opinion if there is insufficient evidence of recovery after treatment, and the great number of second opinions in psychiatric care for patients with persistent depression, only a few studies have been published about their effects.

Methods:

Multilevel analyses were conducted to compare the mean test scores of a group of patients with a persistent depressive disorder who received the intervention of a second opinion with scores from a matched control group, at 3 time points: baseline, intervention, and follow-up.

Results:

A significant decrease in the severity of depression 3 months after the second opinion was found. No effects on quality of life or treatment satisfaction were found.

Limitations:

The study sample was a convenience sample without randomization, and many values were missing in the data. In addition, a 3-month follow-up may have been too short to expect effects of the recommendations from the second opinion. The instructions concerning how to rate treatment satisfaction were also ambiguous.

Conclusions:

A second opinion can be of value for persistent depression. Further research should address the question of whether the effect that was found is caused by the second opinion itself or is the result of subsequent changes in treatment.
A Leg to Stand On: Working With Marginal Decision-making Capacity in a Patient With a Severe Leg Infection and Schizophrenia
Authors: Kichler Zoe , Andermann Lisa , Chow Wendy , Gnanapragasam Gesland , Law Samuel
Published: March 2023

Assessment of a patient’s capacity to make treatment decisions and working with the wishes of a patient with mental illness against the best medically indicated plan is a complex and dynamic task. It is particularly challenging when the course of deterioration of the illness is meandering and slow, and the time horizon for recovery is uncertain, providing no clear point of entry for definitive crisis intervention. High-impact decisions concerning body integrity, such as the amputation of a leg, further complicate the task. To highlight these challenges and complexities, we present the case of a man who suffered from schizophrenia, with a worsening diabetic foot ulcer and suboptimal acceptance of proper wound care. The patient died as a result of his refusal of a proposed amputation to address his life-threatening infection. Medical system and cultural issues are also considered.
Psychodynamic Therapy: An Overview for Trainees and Their Teachers: Part 1–The Basics
Authors: Plakun Eric M.
Published: March 2023

This first column in a series on psychodynamic therapy (PDT) offers an overview of the basics required to understand and master the provision of PDT. It offers a way of understanding what patients struggle with when viewed through a psychodynamic lens and then examines evidence-based core elements of psychotherapy and PDT.
Ai Chi for Balance and Gait in Individuals with Parkinson's Disease: A Pilot Study
Authors: So Billy Chun Lung , Tse Daniel Hon Ting , Kwok Manny Man Ying
Published: March 2023

Background and Purpose:

Parkinson disease (PD) has effects on an individual's balance, and Ai Chi can be used to improve balance and gait performance. The aim of this study was to investigate the effectiveness of Ai Chi in improving the balance and gait of individuals with idiopathic PD.

Method:

Ten individuals with PD at Hoehn and Yahr stages 1-3 were included in this 6-week study. Participants underwent a structured Ai Chi program (1 hour per session, twice weekly) for 6 weeks (12 sessions in total). Balance was assessed at baseline and week 6 using the Timed Up and Go (TUG) test, the Five Times Sit-to-Stand (FTSTS) test, the Four Square Step Test (FSST), the Ten Meter Walk Test (10MWT), and the Sensory Organization Test (SOT). Gait parameters were measured by inertial measurement units and videotaping for 2-dimentional motion analysis. Surface electromyography was used for measuring muscle activity during gait in the bilateral rectus femoris, biceps femoris, gastrocnemius, and tibialis anterior.

Results:

In a pre- and postintervention comparison, significant improvements were observed in the FTSTS, FSST, and TUG scores as well as in the composite, vision, and vestibular scores in the 10MWT and SOT (P < .005). The results indicated improvement in balance. As for the gait analysis, no significant differences were observed in spatiotemporal parameters, including speed, cadence, step length, stride length, step duration, stride duration, swing-phase duration, stance-phase duration, and double support duration. Insignificant changes in the percentage maximum voluntary contraction of all the muscles examined were found, while a significant decrease in maximum voluntary contraction was identified in the left biceps femoris.

Conclusions:

The Ai Chi program produced a significant improvement in balance in individuals with PD, with insignificant results shown in gait. Ai Chi is an appropriate intervention to improve balance in individuals with PD.
The AM-FM Study (Aquatic physiotherapy Management in FibroMyalgia): Exploring Patients' Perceptions About Aquatic Exercise in the Treatment and Management of Fibromyalgia
Authors: Merry Graham , Cairns Mindy C.
Published: March 2023

Background and Purpose:

Fibromyalgia is a complex long-term condition characterized by widespread chronic pain, fatigue, and cognitive disturbances. Between 2.9% and 7% of the UK population may be affected. Hydrotherapy (therapeutic aquatic exercise) is frequently used in the management of fibromyalgia, and most research to date has compared hydrotherapy with a comparator or control group in controlled studies. No study has evaluated the role of hydrotherapy from the patient's perspective. The main purpose of the present study was to explore and examine the experiences and views of patients on hydrotherapy in the treatment and management of fibromyalgia.

Methods:

An online UK-wide survey was conducted with closed- and open-text answers using a convenience sample of participants with fibromyalgia with experience of hydrotherapy.

Results:

In total, 37 participants aged 25 to 79 years (M = 49.2 years) completed the survey; 34 (92%) participants were female, 3 (8%) were male, and 33 (89%) were of White ethnicity. Thirty-one (84%) participants reported hydrotherapy to be beneficial in their management, but 28 (76%) identified barriers to accessing suitable hydrotherapy facilities. Twenty-six (70%) respondents reported beneficial effects of hydrotherapy in relation to pain relief, 25 (68%) reported in relation to physical function, 23 (62%) reported in relation to promoting relaxation, and 21 (57%) reported in relation to an improved sense of well-being. Themes arising from free-text responses included beneficial effects for relaxation and sleep, positive attributes of the properties of the water, and patient preferences for hydrotherapy over land-based exercise.

Discussion and Conclusions:

The findings highlight beneficial effects of hydrotherapy beyond those of pain relief and improved physical function identified by previous studies including relaxation effects and positive effect on sleep, among others. Specific access factors may pose obstacles to continued self-directed hydrotherapy for some individuals.
Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy
Authors: Temu Tecla M. , Polyak Stephen J. , Wanjalla Celestine N. , Mandela Nelson Aringo , Dabee Smritee , Mogaka Jerusha N. , Masyuko Sarah , Longernecker Chris , Shakil Saate , Chohan Bhavna , Page Stephanie T. , Lacourse Sylvia M. , Gitura Bernard , Crothers Kristina , Oyugi Julius , Jaspan Heather , Farquhar Carey , Zifodya Jerry S.
Published: March 2023

Background:

Persons with HIV (PWH) on antiretroviral therapy (ART) have persistent immune activation associated with increased risk for non-AIDS related diseases. Latent tuberculosis infection (LTBI), endemic in Africa, may contribute to this immune dysregulation. We evaluated the impact of HIV and TB co-infection on plasma pro- and anti-inflammatory cytokines among Kenyan adults.

Methods:

We compared data from 221 PWH on long-term ART and 177 HIV-negative adults examining biomarkers of pro-[sCD14, interleukin (IL)-2, IL-6, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-12p70, IL-17A] and anti(IL-4, IL-5, IL-13) inflammatory cytokines, by HIV/LTBI status (HIV+LTBI+, HIV+LTBI−, HIV−LTBI+, HIV−LTBI−). LTBI was diagnosed based on a positive QuantiFERON TB Gold-Plus test in the absence of active TB symptoms. Linear regression was used to evaluate the associations of HIV, LTBI, and HIV/LTBI status with biomarkers adjusting for clinical factors including HIV-specific factors.

Results:

Half of the participants were women and 52% had LTBI. HIV was independently associated with higher sCD14, IL-15, IL-6, IL-4, IL-5. LTBI was independently associated with higher TNF-α, IL-12p70, IL-17A, IL-4, IL-13 in adjusted models (P < 0.05). LTBI status was associated with higher IL-4 and IL-12p70 only among PWH, but not HIV-negative participants (P < 0.05 for interactions). In multivariate analysis, only HIV+LTBI+ demonstrated elevated levels of TNF-α, IL-6, IL-12p70, IL-15, IL-17A, IL4, IL-5, IL-13 in comparison to the HIV−LTBI− (P < 0.05 for all). The effect of LTBI on cytokines among PWH was independent of CD4+ T-cell count and ART duration.

Conclusions:

Despite viral suppression, persons with HIV and LTBI exhibit abnormal cytokine production accompanied by high concentrations of pro- and anti-inflammatory cytokines.
The impact of attrition on the transmission of HIV and drug resistance
Authors: Shen Mingwang , Xiao Yanni , Rong Libin , Zhuang Guihua , Song Chang , Zhao Quanbi , Huang Jinghua , Zhu Qiuying , Liang Shujia , Chen Huanhuan , Li Jianjun , Liao Lingjie , Shao Yiming , Xing Hui , Ruan Yuhua , Lan Guanghua
Published: March 2023

Background:

Attrition due to loss to follow-up or termination of antiretroviral therapy (ART) among HIV-infected patients in care may increase the risk of emergence and transmission of drug resistance (TDR), diminish benefit of treatment, and increase morbidity and mortality. Understanding the impact of attrition on the epidemic is essential to provide interventions for improving retention in care.

Methods:

We developed a comprehensive HIV transmission dynamics model by considering CD4+ cell count dependent diagnosis, treatment, and attrition involving TDR and acquired drug resistance. The model was calibrated by 11 groups HIV/AIDS surveillance data during 2008–2018 from Guangxi, China, and validated by the prevalence of TDR among diagnosed treatment-naive individuals. We aimed to investigate how attrition would affect the transmission of HIV and drug-resistance when expanding ART.

Results:

In the base case with CD4+ cell count dependent per capita attrition rates 0.025∼0.15 and treatment rates 0.23∼0.42, we projected cumulative total new infections, new drug-resistant infections, and HIV-related deaths over 2022–2030 would be 145 391, 7637, and 51 965, respectively. Increasing treatment rates by 0.1∼0.2 can decrease the above total new infections (deaths) by 1.63∼2.93% (3.52∼6.16%). However, even 0.0114∼0.0220 (0.0352∼0.0695) increase in attrition rates would offset this benefit of decreasing infections (deaths). Increasing treatment rates (attrition rates) by 0.05∼0.1 would increase the above drug-resistant infections by 0.16∼0.30% (22.18∼41.15%).

Conclusion:

A minor increase in attrition can offset the benefit of treatment expansion and increase the transmission of HIV drug resistance. Reducing attrition rates for patients already in treatment may be as important as expanding treatment for untreated patients.
Orbital Schwannoma With Frontal Bone Lysis
Authors: Farag Andrew , Farag Samuel , Daigle Patrick
Published: March 2023

Orbital schwannoma is an exceptionally rare cause of ptosis. Diagnosis may be elusive given its slow rate of growth and its various presentations depending on localization. Herein, we report the case of a 50-year-old male who presented to our clinic with a complaint of unilateral, recurrent ptosis of the left eye. He underwent levator palpebrae resection, which was unsuccessful at improving his ptosis. He later represented with acute-onset diplopia for which magnetic resonance imaging was obtained. Magnetic resonance imaging showed a lesion in the superior orbit with secondary bony dehiscence of the orbital roof. Through a vertical lid-split incision, the lesion was removed, and the frontal lobe was observed protruding through the defect in the orbital roof. This case highlights the importance of diagnostic skepticism in the face of recurrent ptosis and emphasizes the utility of the vertical lid-split approach for anterior lesions of the superior orbit.
Denominator of Cranial Vault Asymmetry Index: Choosing Between Longer and Shorter Diagonal Lengths
Authors: Miyabayashi Hiroshi , Saito Katsuya , Kato Risa , Noto Takanori , Nagano Nobuhiko , Morioka Ichiro
Published: March 2023

Since it was proposed in this journal in 2001, the cranial vault asymmetry index (CVAI) has been an important parameter for assessing cranial shape. However, different publications currently use different variables in the denominator of the CVAI formula. We thus investigated the use of long and short diagonal lengths as variables in the denominator of the CVAI formula. We searched the databases of PubMed, Google Scholar, and Scopus for articles published between 2016 and 2022 that cited the original work article of CVAI. Articles were included if they were written in English and if the denominator of the CVAI formula was specified. For multiple articles by the same author, only the most recent article was included. In total, 30 articles were included; 10 articles used the longer diagonal length as the denominator and 20 articles used the shorter diagonal length. No uniform trend was observed by a country or journal of publication. Application of the CVAI formula using different denominators yielded interchangeable results, and the resulting values had only negligible differences clinically. However, it would be necessary to create a standard formula for using the CVAI as a parameter for reporting cranial shape assessments consistently.
The Ability of Comorbidity Indices to Predict Mortality After Heart Transplantation: A Validation of the Danish Comorbidity Index for Acute Myocardial Infarction, Charlson Comorbidity Index, and Elixhauser Comorbidity Index
Authors: Bonnesen Kasper , Mols Rikke E. , Løgstrup Brian , Gustafsson Finn , Eiskjær Hans , Schmidt Morten
Published: March 2023

Background

Advanced heart failure patients often have comorbidities of prognostic importance. However, whether total pretransplantation comorbidity burden predicts mortality in patients treated with heart transplantation (HTx) is unknown. We used population-based hospital and prescription data to examine the ability of the Danish Comorbidity Index for Acute Myocardial Infarction (DANCAMI), DANCAMI restricted to noncardiovascular diseases, Charlson Comorbidity Index, and Elixhauser Comorbidity Index to predict 30-d, 1-y, 5-y, and 10-y all-cause and cardiovascular mortality after HTx.

Methods

We identified all adult Danish patients with incident HTx from the Scandiatransplant Database between March 1, 1995, and December 31, 2018 (n = 563). We calculated Harrell’s C-Statistics to examine discriminatory performance.

Results

The C-Statistic for predicting 1-y all-cause mortality after HTx was 0.58 (95% confidence interval [CI], 0.50-0.65) for a baseline model including age and sex. Adding comorbidity score to the baseline model did not increase the C-Statistics for DANCAMI (0.58; 95% CI, 0.50-0.65), DANCAMI restricted to noncardiovascular diseases (0.57; 95% CI, 0.50-0.64), Charlson Comorbidity Index (0.59; 95% CI, 0.51-0.66), or Elixhauser Comorbidity Index (0.58; 95% CI, 0.51-0.65). The results for 30-d, 5-y, and 10-y all-cause and cardiovascular mortality were consistent.

Conclusions.

After accounting for patient age and sex, none of the commonly used comorbidity indices added predictive value to short- or long-term all-cause or cardiovascular mortality after HTx.
MyKidneyCoach, Patient Activation, and Clinical Outcomes in Diverse Kidney Transplant Recipients: A Randomized Control Pilot Trial
Authors: Pollock McLean D. , Stauffer Nicolas , Lee Hui-Jie , Chow Shein-Chung , Satoru Ito , Moats Lynnette , Swan-Nesbit Sherri , Li Yan , Roberts John K. , Ellis Matthew J. , Diamantidis Clarissa J. , Docherty Sharron L. , Chambers Eileen T.
Published: March 2023

Background:

Kidney transplant (KT) recipients who are not actively engaged in their care and lack self-management skills have poor transplant outcomes, which are disproportionately observed among Black KT recipients. This pilot study aimed to determine whether the MyKidneyCoach app, an mHealth intervention that provides self-management monitoring and coaching, improved patient activation, engagement, and nutritional behaviors in a diverse KT population.

Methods:

This was a randomized, age-stratified, parallel-group, attention-control, pilot study in post-KT patients. Participants were randomized into the attention-control with access to MyKidneyCoach for education and self-management (n = 9) or the intervention with additional tailored nurse coaching (n = 7). Feasibility, acceptability, and clinical outcomes were assessed.

Results:

The acceptability of MyKidneyCoach by System Usability Scale was 67.5 (95% confidence interval [CI], 59.1-75.9). Completion rates based on actively using MyKidneyCoach were 81% (95% CI, 57%-93%) and study retention rate of 73%. Patient activation measure significantly increased overall by a mean of 11 points (95% CI, 3.2-18.8). Additionally, Black patients (n = 7) had higher nutrition self-efficacy scores of 80.5 (95% CI, 74.4-86.7) compared with 75.6 (95% CI, 71.1-80.1) in non-Black patients (n = 9) but lower patient activation measure scores of 69.3 (95% CI, 56.3-82.3) compared with 71.8 (95% CI, 62.5-81) in non-Black patients after 3 mo.

Conclusions:

MyKidneyCoach was easy to use and readily accepted with low attrition, and improvements were demonstrated in patient-reported outcomes. Both Black and non-Black participants using MyKidneyCoach showed improvement in self-management competencies; thus, this intervention may help reduce healthcare inequities in KT.
Unigems: plasmids and parts to facilitate teaching on assembly, gene expression control and logic in E. coli
Authors: Siddall Alex , Williams Abbie Ann , Sanders Jason , Denton Jai A , Madden Dean , Schollar John , Bryk Jarosław
Published: March 2023

Synthetic biology enables the creative combination of engineering and molecular biology for exploration of fundamental aspects of biological phenomena. However, there are limited resources available for such applications in the educational context, where straightforward setup, easily measurable phenotypes and extensibility are of particular importance. We developed Unigems, a set of 10 plasmids that enable classroom-based investigation of gene expression control and biological logic gates to facilitate teaching synthetic biology and genetic engineering. It is built on a high-copy plasmid backbone and is easily extensible thanks to a common primer set that facilitates Gibson Assembly of PCR-generated or synthesised DNA parts into the target vector. It includes two reporter genes with either two constitutive (high- or low-level) or two inducible (lactose- or arabinose-) promoters, as well as a single-plasmid implementation of an AND logic gate. The set can readily be employed in undergraduate teaching settings, during outreach events and for training of iGEM teams. All plasmids have been deposited in Addgene.
Bifidobacterium mellis sp. nov., isolated from the honey stomach of the honey bee Apis mellifera
Authors: Olofsson Tobias C. , Modesto Monica , Pascarelli Stefano , Scarafile Donatella , Mattarelli Paola , Vasquez Alejandra
Published: March 2023

A novel

Bifidobacterium

strain, Bin7NT, was isolated from the honey stomach of the honey bee Apis mellifera. Cells are Gram-positive, non-motile, non-sporulating, facultative anaerobic and fructose 6-phosphate phosphoketolase-positive. Their optimal growth is at 37 °C in anaerobiosis in MRS (De Man, Rogosa and Sharpe) added with cysteine. The honey bee microbiota was composed of several phylotypes of

Bifidobacterium

and

Lactobacillus

. Comparative analysis of 16S rRNA gene sequence similarity revealed that strain Bin7NT grouped with

Bifidobacterium

species originating from honey bees and was closely related to

Bifidobacterium asteroides

DSM 20089T (99.67 % similarity). However, the highest average nucleotide identity and digital DNA–DNA hybridization values of 94.88 and 60.6 %, respectively, were obtained with

Bifidobacterium choladohabitans

JCM 34586T. The DNA G+C content of the type strain is 60.8 mol%. The cell-wall peptidoglycan is of the A4β l-Orn–d-Asp type. The main cellular fatty acids of strain Bin7NT are C18 : 1 ω9c, C16 : 0, C18 : 1 ω7c and C18 : 0. Phenotypic characterization and genotyping based on the genome sequences clearly show that this strain is distinct from the type strains of the so far recognized

Bifidobacterium

species. Thus, Bifidobacterium mellis sp. nov. (Bin7NT=DSM 29108T=CCUG 66113T) is proposed as novel

Bifidobacterium

species.
Paenibacillus mangrovi sp. nov., a novel endophytic bacterium isolated from bark of Kandelia candel
Authors: Huang Zi-Hao , Yang Hui-Lan , Chen Feng , Li Fei-Na , Meng Ling-Jie , Chen Xiao-Hui , Chen Ming-Sheng , Ma Xiao , Zheng Zhou-Qing , Tuo Li
Published: March 2023

A endospore-forming bacterium, designated strain KQZ6P-2T, was isolated from surface-sterilized bark of the mangrove plant Kandelia candel, collected from Maowei Sea Mangrove Nature Reserve in Guangxi Zhuang Autonomous Region, China. Strain KQZ6P-2T was able to grow at NaCl concentrations in the range of 0–3 % (w/v) with optimum growth at 0–1 % (w/v) NaCl. Growth occurred at 20–42 °C (optimal growth at 30–37 °C) and pH 5.5–6.5 (optimal growth at pH 6.5). The 16S rRNA gene sequence similarity between strain KQZ6P-2T and its closest phylogenetic neighbour

Paenibacillus chibensis

JCM 9905T was 98.2 %. Phylogenetic analyses using 16S rRNA gene sequences showed that strain KQZ6P-2T formed a distinct lineage with

Paenibacillus chibensis

JCM 9905T. The draft genome of strain KQZ6P-2T was 5 937 633 bp in size and its DNA G+C content was 47.2mol%. Comparative genome analysis revealed that the average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity values among strain KQZ6P-2T and its related species were below the cut-off levels of 95, 70 and 95.5%, respec-tively. The cell-wall peptidoglycan of strain KQZ6P-2T contained meso-diaminopimelic acid as the diagnostic diamino acid. Major cellular fatty acids were anteiso-C15:0 and C16:0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified aminophospholipids, four unidentified phospholipids, an unidentified aminolipid and five unidentified lipids. Based on phylogenetic, phenotypic and chemotaxonomic data, strain KQZ6P-2T represents a novel species of the genus

Paenibacillus

, for which the name Paenibacillus mangrovi sp. nov. is proposed. The type strain is KQZ6P-2T (=MCCC 1K07172T =JCM 34931T).
In vitro susceptibility profiles of Candida parapsilosis species complex subtypes from deep infections to nine antifungal drugs
Authors: Zhang Wei , Zhan Minghua , Wang Na , Fan Jingjing , Han Xuying , Li Caiqing , Liu Jinlu , Li Jia , Hou Yongwang , Wang Xinsheng , Zhang Zhihua
Published: March 2023

Introduction. The Candida parapsilosis complex can be divided into C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis subtypes. It is uncommon for drug sensitivity tests to type them.

Gap Statement. In routine susceptibility reports, drug susceptibility of C. parapsilosis complex subtypes is lacking.

Aim. The aim of this study is to investigate the antifungal susceptibility and clinical distribution characteristics of the C. parapsilosis complex subtypes causing deep infection in patients.

Methodology. Non-repetitive strains of C. parapsilosis complex isolated from deep infection from 2017 to 2019 were collected. Species-level identification was performed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer and confirmed using ITS gene sequencing, when necessary. Antifungal susceptibility testing was performed using the Sensititre YeastOne system method.

Results. A total of 244 cases were included in the study, including 176 males (72.13 %, 60.69±13.43 years) and 68 females (27.87 %, 60.21±10.59 years). The primary diseases were cancer (43.44 %), cardiovascular disease (25.00 %), digestive system diseases, (18.44 %), infection (6.97 %), and nephropathy (6.15 %). Strains were isolated from the bloodstream (63.11 %), central venous catheters (15.16 %), pus (6.56 %), ascites (5.74 %), sterile body fluid (5.33 %), and bronchoalveolar lavage fluid (BALF, 4.09 %). Of the 244 C. parapsilosis complex strains, 179 (73.26 %) were identified as C. parapsilosis sensu stricto, 62 (25.41 %) were C. orthopsilosis, and three (1.23 %) were C. metapsilosis. Only one C. parapsilosis sensu stricto strain was resistant to anidulafungin, micafungin, caspofungin, and voriconazole, and it was non-wild-type (NWT) to amphotericin B. Furthermore, six C. parapsilosis sensu stricto strains were resistant to fluconazole, and one was dose-dependent susceptible. Five C. parapsilosis sensu stricto strains were NWT to posaconazole. Only one C. orthopsilosis strain was NWT for anidulafungin, micafungin, caspofungin, fluconazole, voriconazole, amphotericin B, and posaconazole, while the rest of the strains were wild-type.

Conclusion.
C. parapsilosis sensu stricto was the main clinical isolate from the C. parapsilosis complex in our hospital. Most strains were isolated from the bloodstream. The susceptibility rate to commonly used antifungal drugs was more than 96 %. Furthermore, most of the infected patients were elderly male cancer patients.
Characterization of the l-arabinofuranose-specific GafABCD ABC transporter essential for l-arabinose-dependent growth of the lignocellulose-degrading bacterium Shewanella sp. ANA-3
Authors: Drousiotis Konstantinos , Herman Reyme , Hawkhead Judith , Leech Andrew , Wilkinson Anthony , Thomas Gavin H.
Published: March 2023

Microbes that have evolved to live on lignocellulosic biomass face unique challenges in the effective and efficient use of this material as food. The bacterium

Shewanella

sp. ANA-3 has the potential to utilize arabinan and arabinoxylan, and uptake of the monosaccharide, l-arabinose, derived from these polymers, is known to be mediated by a single ABC transporter. We demonstrate that the substrate binding protein of this system, GafASw, binds specifically to l-arabinofuranose, which is the rare furanose form of l-arabinose found in lignocellulosic biomass. The structure of GafASw was resolved to 1.7 Å and comparison to

Escherichia coli

YtfQ (GafAEc) revealed binding site adaptations that confer specificity for furanose over pyranose forms of monosaccharides, while selecting arabinose over another related monosaccharide, galactose. The discovery of a bacterium with a natural predilection for a sugar found abundantly in certain lignocellulosic materials suggests an intimate connection in the enzymatic release and uptake of the sugar, perhaps to prevent other microbes scavenging this nutrient before it mutarotates to l-arabinopyranose. This biological discovery also provides a clear route to engineer more efficient utilization of plant biomass components in industrial biotechnology.
Joint associations of pregnancy complications and postpartum maternal renal biomarkers with severe cardiovascular morbidities: A US racially diverse prospective birth cohort study
Authors: Hong Xiumei , Rosenberg Avi Z. , Heymann Jurgen , Yoshida Teruhiko , Waikar Sushrut S. , Ilori Titilayo O. , Wang Guoying , Rebuck Heather , Pearson Colleen , Wang Mei-Cheng , Winkler Cheryl A. , Kopp Jeffrey B. , Wang Xiaobin
Published: March 2023

Rationale & Objective

Pregnancy complications are risk factors for cardiovascular diseases (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD.

Methods

This study included 576 mothers of diverse ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and cystatin C were measured 1-3 days after delivery. CVD during follow-up was defined by physician diagnoses in electronic medical records. Associations of renal biomarkers and pregnancy complications with time-to-CVD events were assessed using Cox proportional hazards models.

Results

During an average of 10.3±3.2 years of follow-up, 34 mothers developed one or more CVD events. Although no significant associations were found between creatinine and risk of CVD, per unit increase of cystatin C (CysC) was associated with a hazard ratio (HR) of 5.21 (95%CI = 1.49-18.2) for CVD. A borderline significant interactive effect was observed between elevated CysC (≥75th percentile) and preeclampsia. Compared to those without preeclampsia and with normal CysC level (<75thpercentile), mothers with preeclampsia and elevated CysC had the highest risk of CVD (HR=3.8, 95%CI = 1.4-10.2), while mothers with preeclampsia only or with elevated CysC only did not have significantly increased CVD risk. Similar synergistic effects for CVD were observed between CysC and preterm delivery.

Conclusions

In this sample of US, traditionally under-represented multi-ethnic high-risk mothers, elevated maternal plasma cystatin C and pregnancy complications synergistically increased risk of CVD later in life. These findings warrant further investigation.

Clinical Perspectives

What is new?

Maternal postpartum elevated levels of cystatin C are independently associated with higher risk of cardiovascular diseases (CVD) later in life.

Maternal pregnancy complications coupled with postpartum elevated levels of cystatin C synergistically increased future risk of CVD.

What are the clinical implications?

These findings, if further confirmed, suggest that women with pregnancy complications and elevated postpartum cystatin C may be at particular high risk for CVD later in life compared to women without these risk factors.
Global disinhibition and corticospinal plasticity for drastic recovery after spinal cord injury
Authors: Yamaguchi Reona , Ueno Satoko , Kawasaki Toshinari , Chao Zenas C. , Mitsuhashi Masahiro , Isa Kaoru , Takei Tomohiko , Kobayashi Kenta , Takahashi Jun , Onoe Hirotaka , Isa Tadashi
Published: March 2023

The induction of large-scale plasticity in the adult brain should be key for recovery from severe damage of the central nervous system. Here, drastic motor recovery was observed after subhemisection spinal cord injury in macaques that received intensive training and cortical electrical stimulation. During recovery, movement-related activity increased in ipsilesional sensorimotor areas and functional connectivity from ipsilesional to contralesional areas was strengthened. Electrical stimulation applied widely across bilateral sensorimotor areas induced muscle twitches in affected and intact forelimbs. The interhemispheric inhibition observed before injury was switched to facilitation. Furthermore, massive re-routing occurred in corticospinal axons from the contralesional motor cortex. Such global disinhibition and massive plasticity would open the workspace for the reorganization of motor networks to recruit novel areas for recovery.

One Sentence Summary

Global disinhibition and corticospinal plasticity for drastic recovery after spinal cord injury in macaque monkeys.
Fgf8regulates first pharyngeal arch segmentation through pouch-cleft interactions
Authors: Zbasnik Nathaniel , Fish Jennifer L.
Published: March 2023

The pharyngeal arches are transient developmental structures that, in vertebrates, give rise to tissues of the head and neck. A critical process underlying the specification of distinct arch derivatives is segmentation of the arches along the anterior-posterior axis. Out-pocketing of the pharyngeal endoderm between the arches is a key mediator of this process, and although it is essential, mechanisms regulating out-pocketing vary between pouches and between taxa. Here, we focus on the patterning and morphogenesis of epithelia associated with the first pharyngeal arch, the first pharyngeal pouch (pp1) and the first pharyngeal cleft (pc1), and the role ofFgf8dosage in these processes. We find that severe reductions ofFgf8levels disrupt both pp1 and pc1 development. Notably, out-pocketing of pp1 is largely robust toFgf8reductions, however, pp1 extension along the proximal-distal axis fails whenFgf8is low. Our data indicate that extension of pp1 requires physical interaction with pc1, and that multiple aspects of pc1 morphogenesis requireFgf8. In particular,Fgf8is required for specification of regional identity in both pp1 and pc1, for localized changes in cell polarity, and for elongation and extension of both pp1 and pc1. Overall, our data indicate a critical role for the lateral surface ectoderm in segmentation of the first pharyngeal arch that has previously been under-appreciated.
Duplicate transcription factorsGT1andVRS1regulate branching and fertile flower number in maize andBrachypodium distachyon
Authors: Gallagher Joseph P. , Man Jarrett , Chiaramida Adriana , Rozza Isabella , Patterson Erin L. , Powell Morgan , Schrager-Lavelle Amanda , Multani Dilbag S. , Meeley Robert , Bartlett Madelaine E.
Published: March 2023

Crop engineering andde novodomestication using genome editing are new frontiers in agriculture. However, outside of well-studied crops and model systems, prioritizing engineering targets remains challenging. Evolution can serve as our guide, revealing high-priority genes with deeply conserved roles. Indeed,GRASSY TILLERS1(GT1),SIX-ROWED SPIKE1(VRS1), and their homologs have repeatedly been targets of selection in domestication and evolution. This repeated selection may be because these genes have an ancient, conserved role in regulating growth repression. To test this, we determined the roles ofGT1andVRS1homologs in maize (Zea mays) and the distantly related grass brachypodium (Brachypodium distachyon) using CRISPR-Cas9 gene editing and mutant analysis.GT1andVRS1have roles in floral development in maize and barley, respectively. Grass flowers are borne in branching structures called spikelets. In maize spikelets, carpels are suppressed in half of all initiated ear flowers. These spikelets can only produce single grains. We show thatgt1; vrs1-like1(vrl1) mutants have derepressed carpels in ear flowers. Importantly, these plants can produce two grains per spikelet. In brachypodium,bdgt1; bdvrl1mutants have more branches, spikelets, and flowers than wildtype plants, indicating conserved roles forGT1andVRS1homologs in growth suppression. Indeed, maizeGT1can suppress growth inArabidopsis thaliana, separated from the grasses byca. 160 million years of evolution. Thus,GT1andVRS1maintain their potency as growth regulators across vast timescales and in distinct developmental contexts. Modulating the activity of these and other conserved genes may be critical in crop engineering.
Viruses encode tRNA and anti-retron to evade bacterial immunity
Authors: Azam Aa Haeruman , Chihara Kotaro , Kondo Kohei , Nakamura Tomohiro , Ojima Shinjiro , Tamura Azumi , Yamashita Wakana , Cui Longzhu , Takahashi Yoshimasa , Watashi Koichi , Kiga Kotaro
Published: March 2023

Retrons are bacterial genetic retroelements that encode reverse transcriptase capable of producing multicopy single-stranded DNA (msDNA) and function as antiphage defense systems. Phages employ several strategies to counter the host defense systems, but no mechanisms for evading retrons are known. Here, we show that tRNATyrand Rad (retron anti-defense) of T5 phage family inhibit the defense activity of retron 78 and a broad range of retrons, respectively. The effector protein of retron 78, ptuAB, specifically degraded tRNATyrleading abortive infection, but phage countervailed this defense by supplying tRNATyr. Rad inhibited retron function by degrading noncoding RNA, the precursor of msDNA. In summary, we demonstrated that viruses encode at least two independent strategies for overcoming bacterial defense systems: anti-defense, such as Rad, and defense canceler, like tRNA.
Identification of small molecule antivirals against HTLV-1 by targeting the hDLG1-Tax-1 protein-protein interaction
Authors: Maseko Sibusiso B. , Brammerloo Yasmine , Van Molle Inge , Sogues Adrià , Martin Charlotte , Gorgulla Christoph , Olivet Julien , Blavier Jeremy , Ntombela Thandokuhle , Delvigne Frank , Arthanari Haribabu , Salehi-Ashtiani Kourosh , Remaut Han , Ballet Steven , Volkov Alexander N. , Twizere Jean-Claude
Published: March 2023

Human T-cell leukemia virus type-1 (HTLV-1) is the first pathogenic retrovirus discovered in human. Although HTLV-1-induced diseases are well characterized and linked to the encoded Tax-1 oncoprotein, there is currently no strategy to target Tax-1 functions with small molecules. Here, we analysed the binding of Tax-1 to the human homolog of the drosophila discs large tumor suppressor (hDLG1/SAP97), a multi-domain scaffolding protein involved in Tax-1-transformation ability. We have solved the structures of the PDZ binding motif (PBM) of Tax-1 in complex with the PDZ1 and PDZ2 domains of hDLG1 and assessed the binding of 10 million molecules by virtual screening. Among the 19 experimentally confirmed compounds, one systematically inhibited the Tax-1-hDLG1 interaction in different biophysical and cellular assays, as well as HTLV-1 cell-to-cell transmission in a T-cell model. Thus, our work demonstrates that interactions involving Tax-1 PDZ-domains are amenable to small-molecule inhibition, which provides a framework for the design of targeted therapies for HTLV-1-induced diseases.
Neural and behavioral correlates of edible cannabis-induced poisoning: characterizing a novel preclinical model
Authors: Amissah Richard Quansah , Kayir Hakan , Talhat Malik Asfandyaar , Hassan Ahmad , Gu Yu , Johnson Ron , Urban Karolina , Khokhar Jibran Y.
Published: March 2023

Accidental exposure to Δ9-tetrahydrocannabinol (THC)-containing edible cannabis, leading to cannabis poisoning, is common in children and pets; however, the neural mechanisms underlying these poisonings remain unknown. Therefore, we examined the effects of acute edible cannabis-induced poisoning on neural activity and behavior. Adult Sprague-Dawley rats (6 males, 7 females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc). Cannabis poisoning was then induced by exposure to a mixture of Nutella (6 g/kg) and THC-containing cannabis oil (20 mg/kg). Subsequently, cannabis tetrad and neural oscillations were examined 2, 4, 8, and 24 h after THC exposure. In another cohort (16 males, 15 females), we examined the effects of cannabis poisoning on learning and prepulse inhibition, and the serum and brain THC and 11-hydroxy-THC concentrations. Cannabis poisoning resulted in sex differences in brain and serum THC and 11-hydroxy-THC levels over a 24-h period. It also caused gamma power suppression in the Cg, dHipp, and NAc in a sex- and time-dependent manner. Cannabis poisoning also resulted in hypolocomotion, hypothermia, and anti-nociception in a time-dependent manner and impairments in learning and prepulse inhibition. Our results suggest that the impairments in learning and information processing may be due to the decreased gamma power in the dHipp and PFC. Additionally, most of the changes in neural activity and behavior appear 2 hours after ingestion, suggesting that interventions at or before this time might be effective in reversing or reducing the effects of cannabis poisoning.