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1.
J Chem Phys ; 161(1)2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38958156

ABSTRACT

Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid-base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems.


Subject(s)
Software , Molecular Dynamics Simulation , Genetic Variation , Algorithms , Thermodynamics , Proteins/chemistry , Crystallization , Nucleic Acids/chemistry
2.
J Clin Invest ; 134(14)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833303

ABSTRACT

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8+ T cell responses mediate disease. Although these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8+ T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8+ T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce ROS and ultimately increased the hypoxic state and granzyme B expression in CD8+ T cells. Importantly, lesions from patients with cutaneous leishmaniasis exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8+ T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as for other inflammatory skin diseases in which cytolytic CD8+ T cells contribute to pathogenesis.


Subject(s)
CD8-Positive T-Lymphocytes , Leishmaniasis, Cutaneous , Neutrophils , Positive Regulatory Domain I-Binding Factor 1 , Animals , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/pathology , Leishmaniasis, Cutaneous/parasitology , Mice , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , Neutrophils/immunology , Neutrophils/pathology , Neutrophils/metabolism , Humans , Positive Regulatory Domain I-Binding Factor 1/genetics , Positive Regulatory Domain I-Binding Factor 1/immunology , Positive Regulatory Domain I-Binding Factor 1/metabolism , Granzymes/metabolism , Granzymes/immunology , Granzymes/genetics , Cell Hypoxia/immunology , Female
3.
Healthcare (Basel) ; 12(10)2024 May 16.
Article in English | MEDLINE | ID: mdl-38786439

ABSTRACT

Spinal disorders are some of the most prevalent health concerns, especially among students. Based on student demographics, this cross-sectional study evaluated the correlation between functional tests (FTs) and spinal range of motion (ROM). This study included 206 students (age = 19.85 ± 1.80 years) from the Vasile Alecsandri University of Bacau. Participants' assessments were conducted using the following tests: (i) Ott, (ii) Schober, (iii) Stibor, (iv) finger-to-floor distance, (v) lateral flexion of the cervical and lumbar spine, and (vi) flexion of the cervical spine. Correlation analyses were evaluated using the Spearman correlation coefficient analysis. The results indicated a very strong relationship between lateral flexion of the lumbar spine on the left (LFLSL) and right (LFLSR) for all departments (r = 0.85 to 0.97, p < 0.05). There was a stronger relationship between FT results and spinal ROM for physical-education-department students compared to students from other departments (n = 17, r = -0.38 to 0.93, p < 0.05). There was no statistically significant correlation between FTs and spinal ROM based on age (p > 0.05). The study results provide evidence of the primary risk factors that predispose students to postural deviations. Practitioners and physiotherapists can utilize these values as a reference for potential therapeutic interventions.

4.
Sports (Basel) ; 12(5)2024 May 14.
Article in English | MEDLINE | ID: mdl-38787001

ABSTRACT

Although myofascial release techniques (MRTs) are commonly used to improve athletes' range of motion (ROM), the effectiveness of MRTs may vary depending on the specific method performed. This systematic review and meta-analysis aimed to evaluate the effects of MRTs on the ROM performance of athletes. (2) Methods: The electronic databases of Cochrane Library, PubMed, Scopus, and Web of Science were searched to identify relevant articles published up to June 2023. This study utilized the PRISMA guidelines, and four databases were searched. The methodological quality of the studies was assessed using the PEDro scale, and the certainty of evidence was reported using the GRADE scale. The overall effect size was calculated using the robust variance estimator, and subgroup analyses were conducted using the Hotelling Zhang test. (3) Ten studies met the inclusion criteria. The overall effect size results indicated that the myofascial release intervention had a moderate effect on ROM performance in athletes when compared to the active or passive control groups. (4) Conclusions: Alternative MRTs, such as myofascial trigger point therapy, can further improve the ROM performance of athletes. Gender, duration of intervention, and joint type may have a moderating effect on the effectiveness of MRTs.

5.
PLoS One ; 19(4): e0302464, 2024.
Article in English | MEDLINE | ID: mdl-38662664

ABSTRACT

BACKGROUND: Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205. METHODOLOGY/PRINCIPAL FINDINGS: The Strong Heart and Strong Heart Family studies have accumulated detailed genetic, cardiovascular risk and event data in geographically dispersed American Indian communities since 1988. Genotypic data and 91 COVID-19 adjudicated deaths or hospitalizations from 2/1/20 through 3/1/23 were identified among 3,780 participants in two subsets. Among 21 candidate variants including genes in the interferon response pathway, APOE, TMPRSS2, TLR3, the HLA complex and the ABO blood group, only rs1205, a 3' untranslated region variant in the CRP gene, showed nominally significant association in T-dominant model analyses (odds ratio 1.859, 95%CI 1.001-3.453, p = 0.049) after adjustment for age, sex, center, body mass index, and a history of cardiovascular disease. Within the younger subset, association with the rs1205 T-Dom genotype was stronger, both in the same adjusted logistic model and in the SOLAR analysis also adjusting for other genetic relatedness. CONCLUSION: A T-dominant genotype of rs1205 in the CRP gene is associated with COVID-19 death or hospitalization, even after adjustment for relevant clinical factors and potential participant relatedness. Additional study of other populations and genetic variants of this gene are warranted.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/genetics , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Female , Male , Middle Aged , SARS-CoV-2/genetics , Aged , Polymorphism, Single Nucleotide , Adult , C-Reactive Protein/genetics , Genetic Predisposition to Disease , Risk Factors , Genotype , Hospitalization , Genetic Variation
6.
Drug Test Anal ; 2023 Dec 03.
Article in English | MEDLINE | ID: mdl-38043944

ABSTRACT

The continued prevalence of xylazine in the illicit drug market has necessitated development of quick and simple methods for identification, including lateral flow immunoassays (also known as "test strips"), like those frequently used to detect fentanyl. This study explored the drug checking applicability of the first publicly available xylazine test strips (XTS) using four sub-studies: reproducibility (i.e., consistency of positive results in a highly-concentrated xylazine solution); limit of detection on a calibration curve of xylazine concentrations; cross-reactivity against 77 commonly encountered drugs, cutting agents, and other structurally similar compounds; and applicability for analyzing community-acquired samples-where 100 drug residue samples were analyzed using XTS, direct analysis in real time mass spectrometry (DART-MS), and gas chromatography tandem mass spectrometry (GC-MS/MS). XTS consistently detected xylazine at concentrations ≥2.5 µg/ml, and XTS results were reproducible. Sensitivity and specificity of XTS were calculated by comparing expected versus obtained results based on xylazine concentration of community-acquired samples measured by GC-MS/MS. XTS consistently detected xylazine in samples with concentration >2 µg/ml and yielded a sensitivity of 0.974, specificity of 1.00, and overall accuracy of 0.986. Cross-reactivity with lidocaine, a common cutting agent, and lack of XTS reactivity with other α2 -agonists found in the illicit drug supply highlight the need to offer consumers comprehensive drug checking services that identify a range of substances and better inform them about drug contents.

7.
bioRxiv ; 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37904953

ABSTRACT

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we find that expression of the cytolytic effector molecule granzyme B is restricted to lesional CD8 T cells in Leishmania - infected mice, suggesting that local cues within inflamed skin induce cytolytic function. Expression of Blimp-1 ( Prdm1 ), a transcription factor necessary for cytolytic CD8 T cell differentiation, is driven by hypoxia within the inflamed skin. Hypoxia is further enhanced by the recruitment of neutrophils that consume oxygen to produce reactive oxygen species, ultimately increasing granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibit hypoxia transcription signatures that correlate with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.

8.
Healthcare (Basel) ; 11(19)2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37830706

ABSTRACT

Although magnetic resonance imaging (MRI) findings are the gold standard for diagnosing herniated discs, there are many limitations to accessing MRI scanning devices in practice. This study aimed to evaluate the relationship between functional tests (the visual analog scale (VAS), the SLUMP test, the Sciatica Bothersomeness Index (SBI), the Oswestry Disability Index (ODI), and the LASEGUE test and MRI findings (LSA, IVDH L4-L5, IVDH L5-S1, DHS L4-L5, and DHS L5-S1) in patients diagnosed with disc herniation. Seventy-eight patients who met the inclusion criteria participated in the study. Radiologists and neurologists evaluated patients with disc herniation. After the disc hernia diagnosis, the patients were referred to a physical therapist for conservative management of the disk hernia. The physical therapists assessed the pain level and performed functional tests on patients. All statistical analyses were performed using R (Core Team) software. The correlation between the measured variables was conducted using the Pearson and Spearman tests. The study results indicated statistically significant correlations between DHS L4-L5 vertebral level and functional tests (VAS: r = 0.49, p = 0.00; SBI: r = 0.44, p = 0.00; ODI: r = 0.49, p = 0.00; LASEGUE: r = -0.48, p = 0.00; SLUMP: r = 0.50, p = 0.00). In conclusion, physiotherapists may prefer functional tests to diagnose the herniated disc, and these functional tests may contribute to performing evidence-based assessments.

9.
J Chem Phys ; 159(5)2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37526158

ABSTRACT

Computational simulation of biomolecules can provide important insights into protein design, protein-ligand binding interactions, and ab initio biomolecular folding, among other applications. Accurate treatment of the solvent environment is essential in such applications, but the use of explicit solvents can add considerable cost. Implicit treatment of solvent effects using a dielectric continuum model is an attractive alternative to explicit solvation since it is able to describe solvation effects without the inclusion of solvent degrees of freedom. Previously, we described the development and parameterization of implicit solvent models for small molecules. Here, we extend the parameterization of the generalized Kirkwood (GK) implicit solvent model for use with biomolecules described by the AMOEBA force field via the addition of corrections to the calculation of effective radii that account for interstitial spaces that arise within biomolecules. These include element-specific pairwise descreening scale factors, a short-range neck contribution to describe the solvent-excluded space between pairs of nearby atoms, and finally tanh-based rescaling of the overall descreening integral. We then apply the AMOEBA/GK implicit solvent to a set of ten proteins and achieve an average coordinate root mean square deviation for the experimental structures of 2.0 Å across 500 ns simulations. Overall, the continued development of implicit solvent models will help facilitate the simulation of biomolecules on mechanistically relevant timescales.


Subject(s)
Amoeba , Solvents/chemistry , Proteins/chemistry , Computer Simulation , Biophysical Phenomena , Thermodynamics
10.
Anal Chim Acta ; 1277: 341634, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37604607

ABSTRACT

Over the last few years, the SARS-CoV-2 pandemic has made the need for rapid, affordable diagnostics more compelling than ever. While traditional laboratory diagnostics like PCR and well-plate ELISA are sensitive and specific, they can be costly and take hours to complete. Diagnostic tests that can be used at the point-of-care or at home, like lateral flow assays (LFAs) are a simple, rapid alternative, but many commercially available LFAs have been criticized for their lack of sensitivity compared to laboratory methods like well-plate ELISAs. The Capillary-Driven Immunoassay (CaDI) device described in this work uses microfluidic channels and capillary action to passively automate the steps of a traditional well-plate ELISA for visual read out. This work builds on prior capillary-flow devices by further simplifying operation and use of colorimetric detection. Upon adding sample, an enzyme-conjugated secondary antibody, wash steps, and substrate are sequentially delivered to test and control lines on a nitrocellulose strip generating a colorimetric response. The end user can visually detect SARS-CoV-2 antigen in 15-20 min by naked eye, or results can be quantified using a smartphone and software such as ImageJ. An analytical detection limit of 83 PFU/mL for SARS-CoV-2 was determined for virus in buffer, and 222 PFU/mL for virus spiked into nasal swabs using image analysis, similar to the LODs determined by traditional well-plate ELISA. Additionally, a visual detection limit of 100 PFU/mL was determined in contrived nasal swab samples by polling 20 untrained end-users. While the CaDI device was used for detecting clinically relevant levels of SARS-CoV-2 in this study, the CaDI device can be easily adapted to other immunoassay applications by changing the reagents and antibodies.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , SARS-CoV-2 , Immunoassay , Enzyme-Linked Immunosorbent Assay , Antibodies , COVID-19 Testing
11.
Int J Pharm ; 639: 122971, 2023 May 25.
Article in English | MEDLINE | ID: mdl-37105242

ABSTRACT

Polymeric microcapsules are extensively investigated as drug delivery systems for a broad range of applications. In the present study, Dexamethasone-loaded carboxylated chitosan (CCS)/poly (vinyl alcohol) (PVA)-based microcapsules were prepared in view of their potential administration by inhalation for the treatment of lung diseases. The crosslinking between PVA and CCS was activated by [4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride] (DMT-MM) and the FTIR results proved the formation of ester bonds between the two polymers. The sizes of the obtained microcapsules are influenced by the ratio between the polymers but also by the concentration of the DMT-MM activator. Moreover, the amount of PVA in the system has an important influence on swelling degree, encapsulation efficiency, drug release degree, biodegradation and protein adsorption. The sample with the highest amount of PVA has the highest crosslinking density and thus the lowest swelling degree and encapsulation efficiency. However, an encapsulation degree of 61.3% was obtained for the sample MCP-6 with the lowest PVA content. The same sample showed the lowest BSA adsorption. A controlled and sustained Dexamethasone release of around 90% was observed in PBS at pH 7.4 and 37 °C during 24 h. All the obtained samples were hemocompatibles and thus can be used as efficient drug delivery systems.


Subject(s)
Chitosan , Polymers , Capsules , Emulsions , Polymers/chemistry , Polyvinyl Alcohol/chemistry , Dexamethasone , Chitosan/chemistry
12.
Polymers (Basel) ; 15(4)2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36850302

ABSTRACT

The present study analyzes (theoretically and experimentally) a drug release process from nanoparticles (polymeric nanocapsules and liposomes). This process is functionalized on the surface with an aptamer. These types of drug release processes can also be included in cream-type formulations. The obtained cream ensures the active targeting of tumor epithelial cells, in the case of skin cancer, because it can be easily administered to the skin by spreading, thus avoiding side effects caused by the toxicity of the drug to healthy cells, increasing both patient compliance and the effectiveness of the treatment. The process of obtaining these formulations is a simple one, easy to use and highly reproductible. The theoretical model, based on the multifractal tunnel effect within the Scale Relativity Theory, considers the system as a complex one. In this model, complexity is replaced with system multifractality, quantified in physical quantities as multifractal dimensions and multifractal functions. The main advantage of this approach consists in the fact that it allows us to obtain information on system behavior at a microscopic level and to evaluate microscopic characteristics of the system, such as intrinsic transparences of the drug molecules, multifractal constants as indicators of the system's complexity, the frequency of interactions within the system and the energy ratio between potential barrier energy and the energy of drug molecules.

14.
Cleft Palate Craniofac J ; 60(5): 645-650, 2023 05.
Article in English | MEDLINE | ID: mdl-35450446

ABSTRACT

OBJECTIVE: To describe a novel orthodontic appliance to prevent pedicle trauma in patients undergoing double-opposing buccal flap surgery for secondary palatal lengthening. DESIGN: Case series. SETTING: Cleft and craniofacial clinic, Johns Hopkins Children's Center. PATIENTS, PARTICIPANTS: Four patients undergoing double-opposing buccal flap surgery for repair of velopharyngeal insufficiency. INTERVENTIONS: Patients were fitted with the device, which consists of a lower lingual holding arch with acrylic bite blocks. MAIN OUTCOME MEASURE: Presence of pedicle trauma postsurgery and tolerability of the device. RESULTS: The appliance was well tolerated in all 4 patients and no biting trauma to the pedicles was observed. CONCLUSIONS: A reliable appliance has been developed to prevent biting trauma to the pedicles in patients undergoing double-opposing buccal flap surgery in the permanent dentition stage.


Subject(s)
Cleft Palate , Plastic Surgery Procedures , Velopharyngeal Insufficiency , Child , Humans , Cleft Palate/surgery , Surgical Flaps , Velopharyngeal Insufficiency/surgery , Velopharyngeal Insufficiency/complications , Orthodontic Appliances , Treatment Outcome , Retrospective Studies
15.
Sci Rep ; 12(1): 21220, 2022 12 08.
Article in English | MEDLINE | ID: mdl-36482065

ABSTRACT

American Indian (AI) children experience significant disparities in asthma prevalence, severity, and burden of disease, yet few asthma education interventions are tested in this population. This study aimed to evaluate the efficacy and feasibility of the BREATHE intervention with parents and AI children, during a 3-year follow-up period (n = 108), using a randomized controlled design. Children with asthma identified by electronic medical records (EMR) were screened and matched with 2 controls. The intervention included an initial educational and 24 months of follow-up. The control group continued their usual care. The primary outcome was the frequency of EMR documented, emergency department (ED) visits or hospitalization for respiratory complaints. There was no statistical difference in mean primary outcomes (1.34 (1.98) vs 1.22 (1.95), - 0.88 to 0.63, 95% CI of the difference, p = 0.75), nor percent with any ED visit or hospitalization (29/53, 55% vs 30/55, 54%, p = 0.99) between the intervention or control groups respectively. After 365 days, there was a borderline significant difference in time to primary outcome. Although limited in power, the present study did not demonstrate a persistent effect of this intervention. We recommend that AI pediatric asthma interventions are culturally-designed, use feasible procedures, and repeat education at least every 12 months.


Subject(s)
American Indian or Alaska Native , Parents , Child , Humans
16.
F S Rep ; 3(4): 366-371, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36568921

ABSTRACT

Objective: To determine whether ovarian volume (OV) alone is an independent marker for metabolic dysfunction in women with suspected androgen excess. Design: Retrospective cohort study. Setting: Tertiary academic reproductive endocrinology clinic. Patients: Women aged ≥21 years recruited/referred for symptoms related to androgen excess. Interventions: Transvaginal ovarian ultrasound, physical and medical evaluation, 2-hour 75-g oral glucose tolerance test (oGTT), and blood sampling. Main Outcome Measures: Prevalence of hyperandrogenism and metabolic dysfunction. Results: This study included 666 women, of whom 412 (61.9%) and 254 had OVs of >10 and ≤10 mL, respectively. An OV of >10 mL was associated with a higher prevalence of hirsutism (65.1% vs. 51.5%) than an OV of ≤10 mL. Polycystic ovary syndrome by the National Institutes of Health 1990 criteria was found in 67.3% and 51.4% of women with OVs of >10 and ≤10 mL, respectively. Metabolic parameters, including body mass index, waist circumference, and 1-hour insulin levels during the oGTT (odds ratio, 1.98; 95% confidence interval, 1.18-3.31), were significantly higher in women with an OV of >10 mL than in those with an OV of ≤10 mL. An OV of ≤10 mL had a 76.3% negative predictive value for hyperinsulinemia at 1 hour. Conclusions: In women with suspected androgen excess, an OV of >10 mL in at least 1 ovary is not associated with metabolic syndrome but is associated with younger age; an increased body mass index and waist circumference; a higher prevalence of hirsutism, oligoovulation, and polycystic ovary syndrome; and a higher 60-minute insulin level during the oGTT. Overall, an increased OV appears to be a good marker for hyperinsulinemia and hyperandrogenism in women suspected of having an androgen excess disorder.

17.
Am J Obstet Gynecol MFM ; 4(4): 100626, 2022 07.
Article in English | MEDLINE | ID: mdl-35351671

ABSTRACT

BACKGROUND: Teamwork and communication gaps are consistently cited as contributors to adverse outcomes in obstetrics. The Critical Care in Obstetrics Course provides an innovative experience by combining brief interactive didactics with the opportunity to practice and implement the knowledge gained with hands-on simulation. Most participants have never worked together, which creates a unique environment to evaluate the importance of teamwork and communication. OBJECTIVE: This study aimed to evaluate the association between teamwork and medical management in high-fidelity critical care simulations. STUDY DESIGN: The participants were separated into multidisciplinary teams and taken through simulations, including placental abruption, hypertensive emergency, eclampsia, sepsis, cardiac arrest, venous thromboembolism, diabetic ketoacidosis, and thyroid storm. Facilitators completed a validated checklist assessment for each group's performance in medical care and teamwork. Each element was rated on a scale from 1 to 5, with 1 being unacceptable and 5 being perfect. We evaluated 5 communication measures, including the use of closed-loop communication and orientation of new team members. A Spearman correlation was used to evaluate the relationship between total medical management and total teamwork scores and specific measures of team communication. Receiver operating characteristic curves were created for total teamwork score as a predictor of good or perfect medical management. RESULTS: A total of 354 multidisciplinary teams participated in 1564 high-fidelity simulations. There was a significant correlation between medical management and teamwork and communication scores for all scenarios. The strongest correlation was for the total teamwork score for all simulations (ρ=0.84). Teamwork scores were highly predictive of medical management scores with an area under the curve of at least 0.88 for all simulations, although this was not significant for diabetic ketoacidosis. CONCLUSION: The quality of teamwork and communication correlated with the quality of clinical performance in newly formed multidisciplinary teams. This demonstrates the importance of teamwork training, with a focus on key communication tools and strategies, among medical providers to optimize the management of complex and emergent obstetrical conditions.


Subject(s)
Diabetic Ketoacidosis , Obstetrics , Clinical Competence , Female , Humans , Patient Care Team , Placenta , Pregnancy
18.
Biol Reprod ; 106(3): 551-567, 2022 03 19.
Article in English | MEDLINE | ID: mdl-35040930

ABSTRACT

Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be due to sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing identified miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n = 113) and parturition (n = 47). Sequencing analysis identified 986 expressed mature miRNAs from female and male placentae at first and third trimester (baseMean>10). Of these, 11 sexually dimorphic (FDR < 0.05) miRNAs were identified in the first and 4 in the third trimester, all upregulated in females, including miR-361-5p, significant in both trimesters. Sex-specific analyses across gestation identified 677 differentially expressed (DE) miRNAs at FDR < 0.05 and baseMean>10, with 508 DE miRNAs in common between female-specific and male-specific analysis (269 upregulated in first trimester, 239 upregulated in third trimester). Of those, miR-4483 had the highest fold changes across gestation. There were 62.5% more female exclusive differences with fold change>2 across gestation than male exclusive (52 miRNAs vs 32 miRNAs), indicating miRNA expression across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex-independent and sex-specific placenta miRNA atlas across gestation, which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences.


Subject(s)
MicroRNAs , Placenta , Sex Characteristics , Epigenesis, Genetic , Female , Humans , Male , MicroRNAs/genetics , Placenta/metabolism , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Third
19.
J Clin Med ; 10(21)2021 Oct 29.
Article in English | MEDLINE | ID: mdl-34768611

ABSTRACT

An observational study on 22 patients presenting with acute limb ischemia and SARS-CoV-2 infection, and without any other embolic risk factors, was performed. All patients were classified according to Rutherford classification for acute limb ischemia. The primary goal of this study was to assess the risk of amputation in these patients after revascularization procedures. The secondary goal was to find the correlation between acute limb ischemia (ALI) severity, patient comorbidities, risk of death, and the association of SARS-CoV-2 infection. The patients were treated by open surgery (18 patients-81.81%) or by the means of endovascular techniques (four patients-18.18%). The amputation-free survival rate was 81.81% in hospital and 86.36% at 1-month follow-up. In this study, the presence of SARS-CoV-2 infection did not influence the amputation-free survival rate: it was only the risk factor for the arterial thrombosis and the trigger for the acute ischemic event. The application of the standard treatment-open surgery or endovascular revascularization-in patients with acute limb ischemia and SARS-CoV-2 infection represents the key to success for lower limb salvage.

20.
Healthcare (Basel) ; 9(11)2021 Oct 31.
Article in English | MEDLINE | ID: mdl-34828528

ABSTRACT

The aim of the present study was to examine the prevalence of work-related musculoskeletal complaints and potential risk factors among Romanian surgeons. Ninety-five surgeons of different specialties (62.11% males) completed a questionnaire about work-related musculoskeletal complaints (WMSCs). Ninety-one surgeons (95.78%) experienced WMSCs at least in one body part in the last year. Most surgeons reported pain in four body parts (33.68%). The most common WMSCs were reported on the lower back (74.73%), followed by complaints in the neck region (55.79%), shoulder and upper back (46.32%), knee (31.58%), wrist-hand (16.84%), elbow (14.74%), hip (11.58%) and ankle-foot (4.21%). Surgeons rated their pain more severe on upper back, lower back and knees. A higher percentage of male surgeons reported upper back pain (χ2(1) = 5.818, p = 0.015). Significant age differences were found between the reported pain sites (F8,278 = 2.666, p = 0.008); the surgeons reporting wrist-hand pain were younger than those reporting neck, shoulders, elbows, dorsal and lumbar pain. Surgeons with significantly less experience in years reported significantly more WMSCs in wrist-hand, hip and ankle-foot regions compared with those more experienced (p < 0.05). Surgeons are at high risk of developing work-related musculoskeletal complaints, which affects both their professional and personal life. Further studies are needed to identify all risk factors and ergonomic strategies to reduce the prevalence and the negative impact of WMSCs.

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