-
Journal of Magnetic Resonance (San... May 2024Solution NMR spectroscopy has tremendous potential for providing atomic resolution insights into the interactions between proteins and nucleic acids partitioned into...
Solution NMR spectroscopy has tremendous potential for providing atomic resolution insights into the interactions between proteins and nucleic acids partitioned into condensed phases of phase-separated systems. However, the highly viscous nature of the condensed phase challenges applications, and in particular, the extraction of quantitative, site-specific information. Here, we present a delayed decoupling-based HMQC pulse sequence for methyl-TROSY studies of 'client' proteins and nucleic acids partitioned into 'scaffold' proteinaceous phase-separated solvents. High sensitivity and excellent quality spectra are recorded of a nascent form of superoxide dismutase and of a small RNA fragment partitioned into CAPRIN1 condensates.
Topics: RNA; Nuclear Magnetic Resonance, Biomolecular; Protein Folding; Proteins; Superoxide Dismutase; Biomolecular Condensates; Algorithms
PubMed: 38626504
DOI: 10.1016/j.jmr.2024.107667 -
Cureus Mar 2024This case outlines the complications of Roux-en-Y gastric bypass surgery (RYGBS) and demonstrates clinical manifestations of several vitamin deficiencies. We present a...
This case outlines the complications of Roux-en-Y gastric bypass surgery (RYGBS) and demonstrates clinical manifestations of several vitamin deficiencies. We present a 45-year-old female patient who was admitted to our hospital with generalized weakness, anasarca, hypotension, and failure to thrive, a year after she had her RYGBS. After the procedure, she had nausea, vomiting, and diarrhea with progressive inability to tolerate any oral intake. Subsequently, the patient lost over 200 pounds and got bedridden. Initially, after the procedure, the patient had a dilatation of her anastomotic stricture, but after her surgeon moved out of town she was lost to follow up until she presented to our hospital. Upon arrival, the patient was hypotensive, tachycardic, and appeared dehydrated. The exam also revealed several clinical manifestations of vitamin deficiencies including dermatitis concerning Pellagra, follicular hyperkeratosis, and Bitot spots. Laboratory data showed significantly low albumin, protein, acute kidney injury, and several electrolyte abnormalities. The patient had to be admitted to the ICU for pressure support along with colloid and electrolyte replacement. An Esophagogastroduodenoscopy (EGD) was performed which revealed a clean-based ulcer and a 10-mm anastomotic stricture. She was started on Total Parenteral Nutrition (TPN). After the dilatation of the stricture, the patient was able to tolerate oral intake and TPN was subsequently discontinued upon discharge. The patient was educated extensively on the importance of compliance with daily vitamin supplementation and regular follow-up with bariatric physicians at discharge.
PubMed: 38618465
DOI: 10.7759/cureus.56101 -
The Journal of Physical Chemistry. B Apr 2024The molecular dynamics study of thermotropic mesogens exhibiting the crystal phases is valuable in unraveling the complex global (collective) and local (noncollective)...
The molecular dynamics study of thermotropic mesogens exhibiting the crystal phases is valuable in unraveling the complex global (collective) and local (noncollective) motions executed by liquid crystal molecules, which would further advance the existing knowledge on orientationally disordered crystalline (ODIC) phases. Toward the fulfillment of such a task, a combined nuclear magnetic resonance (NMR) relaxometry approach employing the fast field cycling (FFC) NMR (10 kHz-30 MHz) and high-field pulsed NMR (400 MHz) techniques is utilized to sample the broad frequency range offered by molecular motions in the crystal phase of 4-(trans-4'--hexylcyclohexyl)-isothiocyanatobenzene (6CHBT). The validity of the observed relaxation data is tested and interpreted by the Bloembergen-Purcell-Pound (BPP) model involving the superposition of four mutually independent Lorentzian spectral densities, reflecting molecular dynamical processes on different time scales. The salient feature of the detailed analysis reveals that the lengthening of temporal dynamics in the crystal phase due to molecular rotations by jumps, which are of intermolecular origin, is evident and further supports the presence of collective-like local dynamics. The analysis does permit decoupling of the molecular reorientations about their short axes (∼100 ns) as well as long axes (∼50 ns) and methyl group rotations (∼0.5 ns) on distinct time scales. The activation energies for reorientations about the short axes and methyl group rotations are found to be 27.3 ± 2.7 and 15.8 ± 1.1 kJ/mol, respectively. The fast methyl rotations in the crystal phase of 6CHBT obtained from FFC NMR are further well complemented by high-field NMR, where H NMR line shapes are relatively narrow when compared to those of the nematic phase.
PubMed: 38616575
DOI: 10.1021/acs.jpcb.3c08259 -
Molecules (Basel, Switzerland) Mar 2024Cancer is one of the leading causes of death worldwide, making the search for alternatives for its control a critical issue. In this context, exploring alternatives from... (Review)
Review
Cancer is one of the leading causes of death worldwide, making the search for alternatives for its control a critical issue. In this context, exploring alternatives from natural sources, such as certain vegetables containing a variety of secondary metabolites with beneficial effects on the body and that play a crucial role in the fight against cancer, is essential. Among the compounds with the greatest efficacy in controlling this disease, those with antioxidant activity, particularly phenolic com-pounds, stand out. A remarkable example of this group is protocatechuic acid (PCA), which has been the subject of various revealing research on its activities in different areas. These studies sustain that protocatechuic acid has anti-inflammatory, antimutagenic, antidiabetic, antiulcer, antiviral, antifibrogenic, antiallergic, neuroprotective, antibacterial, anticancer, antiosteoporotic, anti-aging, and analgesic properties, in addition to offering protection against metabolic syndrome and con-tributing to the preservation of hepatic, renal, and reproductive functionality. Therefore, this paper aims to review the biological activities of PCA, focusing on its anticancer potential and its in-volvement in the control of various molecular pathways involved in tumor development, sup-porting its option as a promising alternative for cancer treatment.
Topics: Humans; Hydroxybenzoates; Neoplasms; Phenols
PubMed: 38611719
DOI: 10.3390/molecules29071439 -
Cureus Mar 2024Squamous cell carcinoma (SCC) is the second leading form of skin cancer. In the elderly population, surgery may carry more risk and significant morbidity in comparison...
Squamous cell carcinoma (SCC) is the second leading form of skin cancer. In the elderly population, surgery may carry more risk and significant morbidity in comparison to less invasive forms of treatment. This case report describes the successful use of intralesional 5-fluorouracil (IL5-FU) to treat cutaneous squamous cell carcinoma (cSCC). A 98-year-old white woman presented in early May 2017 with a 3.5-cm rapidly growing crusted nodule on her left proximal-lateral arm. She had a past medical history of chronic obstructive pulmonary disease, atrial fibrillation, and heart failure. The patient also had a frail body habitus and weighed 80 pounds. Physical examination revealed a large, ulcerated, crateriform mass on the left proximal-lateral arm. A shave biopsy was performed, which revealed a well-differentiated SCC, composed of nodular masses of neoplastic squamous cells with atypical nuclei, keratin pearl formation, and scattered mitotic figures with surrounding fibrosis and inflammation. The patient was wheelchair-bound and oxygen-dependent and, thus, not considered a good surgical or radiation candidate. Treatment was decided with 5-fluorouracil. At a four-week follow-up appointment, there was no visible or palpable evidence of the tumor. There was no sign of recurrence at three months, indicating treatment success. The patient later died due to cardiac arrest in September 2017. The elderly population with cSCC can benefit from intervention and treatment with IL5-FU when surgery is not an option due to patient comorbidities. IL5-FU can potentially be used in areas where access to a dermatologist, surgeon, or surgical services is limited.
PubMed: 38590475
DOI: 10.7759/cureus.55855 -
BMC Musculoskeletal Disorders Apr 2024Patients seeking medical care for back pain often have coexisting painful joints and the effects of different combinations and number of coexisting pain sites (hip,...
BACKGROUND
Patients seeking medical care for back pain often have coexisting painful joints and the effects of different combinations and number of coexisting pain sites (hip, knee, foot/ankle) to back pain on physical function domains and quality of life rating are not yet established. The purpose of this study was to determine the differences in functional outcomes and QOL among individuals with back pain who have concurrent additional pain sites or no pain sites.
METHODS
Data from the Osteoarthritis Initiative (OAI) cohort were used for this cross-sectional analysis. Men and women aged 45-79 years with back pain were binned into nine groups by presence or not of coexisting hip, knee, ankle/foot pain and combinations of these sites (N = 1,642). Healthy controls reported no joint pain. Main outcomes included Knee Injury and Osteoarthritis Outcome score (KOOS; quality of life and function-sports-and-recreation), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC; Activities of Daily Living, Pain), Medical Outcomes Short Form-12 (SF-12) Physical Component score, and self-reported function in last 7-30 days (lifting 25-pound objects, housework). 20-m and 400-m walk times and gait speed and repeated chair rise test times were collected.
RESULTS
Compared to back pain alone, pain at all five sites was associated with 39%-86% worse KOOS, WOMAC, and SF-12 scores (p < .0001). Back-Hip and Back-Knee did not produce worse scores than Back pain alone, but Back-Hip-Knee and Back-Knee-Ankle/Foot did. The 20-m, 400-m walk, and repeated chair times were worse among individuals with pain at all five sites. Additional hip and knee sites to back pain, but not ankle/foot, worsened performance-based walk times and chair rise scores.
CONCLUSIONS
The number and type of coexistent lower body musculoskeletal pain among patients with back pain may be associated with perceived and performance-based assessments. Management plans that efficiently simultaneously address back and additional coexistent pain sites may maximize treatment functional benefits, address patient functional goals in life and mitigate disability.
Topics: Male; Humans; Female; Musculoskeletal Pain; Osteoarthritis, Knee; Quality of Life; Activities of Daily Living; Cross-Sectional Studies; Knee Joint; Arthralgia; Back Pain
PubMed: 38589851
DOI: 10.1186/s12891-024-07393-2 -
Archives of Disease in Childhood Apr 2024To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections.
OBJECTIVE
To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections.
DESIGN
Multi-centre observational cohort study using data from 2009 to 2018 clinical records.
SETTING
Canadian children's hospitals (7) and community hospitals (3).
PATIENTS
Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections.
INTERVENTIONS
Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation.
MAIN OUTCOME MEASURES
Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates.
RESULTS
Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018.
CONCLUSIONS
Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes.
PubMed: 38589203
DOI: 10.1136/archdischild-2023-326175 -
Research Square Mar 2024Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for for 10-15% of childhood lymphomas. Despite the observation that more than 90% of...
Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase ( rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL(ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA-sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (), transcription (), and epigenetic regulators (E). Gene expression and methylation profiling consistently subclassified ALK+ ALCLs into two groups characterized by diferential ALK expression levels. The ALK-low group showed enrichment of pathways associated with immune response, cytokine signaling, and a hypermethylated predominant pattern compared to the ALK- high group, which had more frequent copy number changes, and was enriched with pathways associated with cell growth, proliferation, metabolic pathways, and. Taken together, these findings suggest that there is molecular heterogeneity within pediatric ALK+ALCL, predicting distinct biological mechanisms that may provide novel insights into disease pathogenesis and represent prognostic markers.
PubMed: 38585847
DOI: 10.21203/rs.3.rs-4145750/v1 -
PEC Innovation Dec 2024End-of-life experiences can have important implications for the meaning-making and communication of bereaved family members, particularly due to (in)access to formal...
OBJECTIVE
End-of-life experiences can have important implications for the meaning-making and communication of bereaved family members, particularly due to (in)access to formal healthcare services (i.e., palliative care and hospice). Grounded in Communicated Narrative Sense-Making theory, this study extends knowledge about how the stories told about end-of-life by bereaved family members affect and reflect their sense-making, well-being and importantly, potential disparities in end-of-life care.
METHODS
Semi-structured interviews with 25 bereaved individuals were conducted regarding their experiences with the terminal illness and death of an immediate family member. Using a framework of family bereavement narratives, a cross-case data analysis demonstrated qualitative patterns between (in)access to end-of-life care and how participants framed bereavement stories.
RESULTS
Four themes illustrated the continuum of communication that families engaged in when making sense of end-of-life experiences, including , , and .
INNOVATION
This innovative qualitative connection between family members' bereavement stories and end-of-life care emphasizes the importance of employing a health equity lens within hospice and palliative care, especially in addressing the important aim of comprehensively supporting families even when illness ends. This study demonstrates that access to, quality of, and imagining beyond current structures for EOL may be vital factors for facilitating effective sense-making for the dying and their family systems.
CONCLUSION
These findings illustrate the potential interconnections between (in)access to end-of-life care, sense-making, and communication for individuals and families experiencing terminal illness and bereavement.
PubMed: 38576418
DOI: 10.1016/j.pecinn.2024.100276 -
Journal of Electromyography and... Jun 2024Cortical motor neuron activity appears to drive lower motor neurons through two distinct frequency bands: the β range (15-30 Hz) during weak muscle contractions and γ...
Cortical motor neuron activity appears to drive lower motor neurons through two distinct frequency bands: the β range (15-30 Hz) during weak muscle contractions and γ range (30-50 Hz) during strong contractions. It is unknown whether the frequency of cortical drive shifts continuously or abruptly between the β and γ frequency bands as contraction strength changes. Intermuscular coherence (IMC) between synergistic arm muscles was used to assess how the frequency of common neuronal drive shifts with increasing contraction strength. Muscle activity was recorded by surface electromyography (EMG) from the biceps and brachioradialis in nine healthy adults performing 30-second isometric holds with added loads. IMC was calculated across the two muscle groups during the isometric contraction. Significant IMC was present in the 20 to 50 Hz range with all loads. Repeated measures ANOVA show the peak frequency of IMC increased significantly when load was added, from a peak of 32.7 Hz with no added load, to 35.3 Hz, 35.7 Hz, and 36.3 Hz with three-, five-, and ten-pound loads respectively. An increase in IMC frequency occurs in response to added load, suggesting that cortical drive functions over a range of frequencies as a function of an isometric contraction against load.
Topics: Humans; Muscle, Skeletal; Male; Electromyography; Isometric Contraction; Female; Adult; Weight-Bearing; Arm; Young Adult
PubMed: 38574588
DOI: 10.1016/j.jelekin.2024.102881