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Science Advances Jun 2024Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions in alcohol use disorder. Chronic alcohol exposure alters synaptic...
Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions in alcohol use disorder. Chronic alcohol exposure alters synaptic function and neuronal excitability in the dorsal striatum, but it remains unclear how it affects BG output that is mediated by the substantia nigra pars reticulata (SNr). Here, we describe a neuronal subpopulation-specific synaptic organization of striatal and subthalamic (STN) inputs to the medial and lateral SNr. Chronic alcohol exposure (CIE) potentiated dorsolateral striatum (DLS) inputs but did not change dorsomedial striatum and STN inputs to the SNr. Chemogenetic inhibition of DLS direct pathway neurons revealed an enhanced role for DLS direct pathway neurons in execution of an instrumental lever-pressing task. Overall, we reveal a subregion-specific organization of striatal and subthalamic inputs onto the medial and lateral SNr and find that potentiated DLS-SNr inputs are accompanied by altered BG control of action execution following CIE.
Topics: Animals; Neuronal Plasticity; Basal Ganglia; Substantia Nigra; Ethanol; Corpus Striatum; Male; Mice; Neurons; Alcoholism; Neural Pathways
PubMed: 38941461
DOI: 10.1126/sciadv.adm6951 -
Medicine Jun 2024This study aimed to evaluate the clinical and radiological features of the patella fixation technique using Toggleloc suspension system in a single ellipsoidal blind...
BACKGROUND
This study aimed to evaluate the clinical and radiological features of the patella fixation technique using Toggleloc suspension system in a single ellipsoidal blind patellar tunnel during medial patellofemoral ligament (MPFL) reconstruction.
METHODS
This study included 52 patients (25 men, 27 women) who underwent MPFL reconstruction using a semitendinosus tendon graft. The graft was fixed to the ellipsoidal single blind tunnel opened on the medial side of the patella with an endobutton and was fixed to the femoral tunnel by using bioabsorbable screw. Clinical scores (Kujala score, Lysholm score, Tegner activity score and the visual analog scale [VAS] score) were evaluated preoperatively and at the end-follow up. Preoperative and postoperative radiological measurements (trochlea depth, sulcus angle, patellar height, patellar congruence angle, patellar tilt angle and lateral patellofemoral angle) were evaluated with X-ray (Merchant X-ray, anteroposterior and lateral radiography) and computed tomography (CT) of the knee.
RESULTS
Postoperative patellar redislocation or subluxation was not observed in any patient. Patellar congruence angle, patellar tilt angle and lateral patellofemoral angle mean values were found to return to normal values in the postoperative period and the results were statistically significant. Also statistically significant improvement in all clinical scores postoperatively. According to the Insall-Salvati index (ISI) and Caton-Deschamps index (CDI) on lateral radiography of the knee at 30° flexion, patellar height decreased in the postoperative period statistically significant. The CDI was above 1.3 in 17 (%32) of our patients. Thirteen of these values decreased to normal values. No radiological progression of patellofemoral osteoarthritis was observed in all patients at the final follow-up evaluation.
CONCLUSION
In cases of patellofemoral instability, fixation of the tendon graft in blind ellipsoid tunnel using the Toggleloc suspension system provides satisfactory patellar graft fixation strength, significant functional improvement and a low failure rate.
Topics: Humans; Female; Male; Adult; Patellofemoral Joint; Follow-Up Studies; Patella; Plastic Surgery Procedures; Young Adult; Ligaments, Articular; Treatment Outcome; Adolescent
PubMed: 38941440
DOI: 10.1097/MD.0000000000038379 -
Medicine Jun 2024Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed... (Review)
Review
RATIONALE
Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed through intraoperative rapid pathology, this condition generally has a favorable prognosis. Nevertheless, comprehensive treatment guidelines across all disease stages are lacking, the purpose of this study is to report 1 case of the disease and propose the treatment plan for each stage of the disease.
PATIENT CONCERNS
A patient presented with thyroid swelling, classified as C-TIRADS 4A following a physical examination. Preoperative thyroid puncture identified papillary thyroid carcinoma, and genetic testing revealed a BRAF gene exon 15-point mutation. Ancillary tests showed a slightly decreased thyroid stimulating hormone (TSH) level (0.172) with no other significant abnormalities.
DIAGNOSES
Preoperative fine-needle aspiration cytology (FNAC) confirmed right-side thyroid cancer. Intraoperative exploration uncovered a TGDC and intraoperative rapid pathology confirmed thyroglossal duct carcinoma.
INTERVENTIONS
A Sistrunk operation and ipsilateral thyroidectomy were performed.
OUTCOMES
Postoperative recovery was satisfactory.
LESSONS
Thyroglossal duct carcinoma is a rare disease affecting the neck. Due to limited clinical cases and the favorable prognosis associated with this condition, there is currently no established set of diagnostic and treatment guidelines. According to tumor size, lymph node metastasis, thyroid status and other factors, the corresponding treatment methods were established for each stage of thyroglossal duct cancer, which laid the foundation for the subsequent treatment development of this disease.
Topics: Humans; Thyroglossal Cyst; Thyroid Neoplasms; Thyroid Cancer, Papillary; Female; Thyroidectomy; Male; Proto-Oncogene Proteins B-raf; Adult; Biopsy, Fine-Needle
PubMed: 38941410
DOI: 10.1097/MD.0000000000038540 -
PloS One 2024Pain in conjunction with surgery for ulnar nerve entrapment at the elbow is seldom highlighted in the literature. This study aimed to explore patients' experiences of...
PURPOSE
Pain in conjunction with surgery for ulnar nerve entrapment at the elbow is seldom highlighted in the literature. This study aimed to explore patients' experiences of living with chronic pain (≥3 months duration) in conjunction with surgery for ulnar nerve entrapment at the elbow, the consequences and the coping strategies applied.
MATERIAL AND METHODS
In-depth interviews were conducted with 10 participants aged 18-60 years. The narratives were analyzed using an inductive approach and content-analysis.
RESULTS
The analysis revealed seven main categories: "Physical symptoms/impairments" and "Mood and emotions"comprise symptoms caused by ulnar nerve entrapment at the elbow and chronic pain; "Consequences in daily life" includes challenges and obstacles in every-day life, impact on leisure activities and social life; "Struggling with self-image" embraces experiences closely related to identity; "Coping strategies" covers adaptive resources; "Experience of relief "describes perceived improvements; "Key message for future care" comprises important aspects for healthcare providers to consider.
CONCLUSIONS
The results clarify the need for healthcare personnel to adopt a biopsychosocial approach when treating patients with ulnar nerve entrapment at the elbow. Emotional symptoms and sleep disturbances should be identified and treated properly since they contribute to the heavy burden experienced by the individual.
Topics: Humans; Adult; Female; Male; Middle Aged; Ulnar Nerve Compression Syndromes; Adolescent; Chronic Pain; Elbow; Young Adult; Qualitative Research; Adaptation, Psychological; Ulnar Nerve
PubMed: 38941288
DOI: 10.1371/journal.pone.0306327 -
ELife Jun 2024Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we...
Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
Topics: SARS-CoV-2; Coronavirus Nucleocapsid Proteins; Mutation; COVID-19; Humans; Intrinsically Disordered Proteins; Phosphoproteins; Nucleocapsid Proteins; Thermodynamics; Protein Stability
PubMed: 38941236
DOI: 10.7554/eLife.94836 -
ELife Jun 2024Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought...
Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here, we show results that GABAergic scaling can act to homeostatically control spiking levels. We found that perturbations which increased or decreased spiking in cortical cultures triggered multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we found that changes in AMPA receptor (AMPAR) or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling represents a stronger candidate for spike rate homeostat than AMPAergic scaling.
Topics: Receptors, AMPA; Animals; Action Potentials; Synapses; Neuronal Plasticity; GABAergic Neurons; Synaptic Transmission; Cells, Cultured; gamma-Aminobutyric Acid; Homeostasis
PubMed: 38941139
DOI: 10.7554/eLife.87753 -
GigaScience Jan 2024Colletotrichum fungi infect a wide diversity of monocot and dicot hosts, causing diseases on almost all economically important plants worldwide. Colletotrichum is also a...
BACKGROUND
Colletotrichum fungi infect a wide diversity of monocot and dicot hosts, causing diseases on almost all economically important plants worldwide. Colletotrichum is also a suitable model for studying gene family evolution on a fine scale to uncover events in the genome associated with biological changes.
RESULTS
Here we present the genome sequences of 30 Colletotrichum species covering the diversity within the genus. Evolutionary analyses revealed that the Colletotrichum ancestor diverged in the late Cretaceous in parallel with the diversification of flowering plants. We provide evidence of independent host jumps from dicots to monocots during the evolution of Colletotrichum, coinciding with a progressive shrinking of the plant cell wall degradative arsenal and expansions in lineage-specific gene families. Comparative transcriptomics of 4 species adapted to different hosts revealed similarity in gene content but high diversity in the modulation of their transcription profiles on different plant substrates. Combining genomics and transcriptomics, we identified a set of core genes such as specific transcription factors, putatively involved in plant cell wall degradation.
CONCLUSIONS
These results indicate that the ancestral Colletotrichum were associated with dicot plants and certain branches progressively adapted to different monocot hosts, reshaping the gene content and its regulation.
Topics: Colletotrichum; Transcriptome; Genome, Fungal; Evolution, Molecular; Phylogeny; Adaptation, Physiological; Gene Expression Profiling; Plant Diseases
PubMed: 38940768
DOI: 10.1093/gigascience/giae036 -
Journal of the Korean Association of... Jun 2024Dentoalveolar (DA) trauma, which can involve tooth, alveolar bone, and surrounding soft tissues, is a significant dentofacial emergency. In emergency settings,...
Dentoalveolar (DA) trauma, which can involve tooth, alveolar bone, and surrounding soft tissues, is a significant dentofacial emergency. In emergency settings, physicians might lack comprehensive knowledge of timely procedures, causing delays for specialist referral. This systematic review assesses the literature on isolated DA fractures, emphasizing intervention timing and splinting techniques and duration in both children and adults. This systematic review adhered to PRISMA guidelines and involved a thorough search across PubMed, Google Scholar, Semantic Scholar, and the Cochrane Library from January 1980 to December 2022. Inclusion and exclusion criteria guided study selection, with data extraction and analysis centered on demographics, etiology, injury site, diagnostics, treatment timelines, and outcomes in pediatric (2-12 years) and adult (>12 years) populations. This review analyzed 26 studies, categorized by age into pediatrics (2-12 years) and adults (>12 years). Falls were a common etiology, primarily affecting the anterior maxilla. Immediate management involved replantation, repositioning, and splinting within 24 hours (pediatric) or 48 hours (adult). Composite resin-bonded splints were common. Endodontic treatment was done within a timeframe of 3 days to 12 weeks for children and 2-12 weeks for adults. Tailored management based on patient age, tooth development stage, time elapsed, and resource availability is essential.
PubMed: 38940648
DOI: 10.5125/jkaoms.2024.50.3.123 -
MSphere Jun 2024Bacterial conjugation systems pose a major threat to human health through their widespread dissemination of mobile genetic elements (MGEs) carrying cargoes of antibiotic...
UNLABELLED
Bacterial conjugation systems pose a major threat to human health through their widespread dissemination of mobile genetic elements (MGEs) carrying cargoes of antibiotic resistance genes. Using the Cre Recombinase Assay for Translocation (CRAfT), we recently reported that the IncFV pED208 conjugation system also translocates at least 16 plasmid-encoded proteins to recipient bacteria. Here, we deployed a high-throughput CRAfT screen to identify the repertoire of chromosomally encoded protein substrates of the pED208 system. We identified 32 substrates encoded by the W3110 genome with functions associated with (i) DNA/nucleotide metabolism, (ii) stress tolerance/physiology, (iii) transcriptional regulation, or (iv) toxin inhibition. The respective gene deletions did not impact pED208 transfer proficiencies, nor did Group 1 (DNA/nucleotide metabolism) mutations detectably alter the SOS response elicited in new transconjugants upon acquisition of pED208. However, MC4100(pED208) donor cells intrinsically exhibit significantly higher SOS activation than plasmid-free MC4100 cells, and this plasmid carriage-induced stress response is further elevated in donor cells deleted of several Group 1 genes. Among 10 characterized substrates, we gained evidence of C-terminal or internal translocation signals that could function independently or synergistically for optimal protein transfer. Remarkably, nearly all tested proteins were also translocated through the IncN pKM101 and IncP RP4 conjugation systems. This repertoire of protein substrates, here termed the F plasmid "conjutome," is thus characterized by functions of potential benefit to new transconjugants, diverse TSs, and the capacity for promiscuous transfer through heterologous conjugation systems.
IMPORTANCE
Conjugation systems comprise a major subfamily of the type IV secretion systems (T4SSs) and are the progenitors of a second large T4SS subfamily dedicated to translocation of protein effectors. This study examined the capacity of conjugation machines to function as protein translocators. Using a high-throughput reporter screen, we determined that 32 chromosomally encoded proteins are delivered through an F plasmid conjugation system. The translocated proteins potentially enhance the establishment of the co-transferred F plasmid or mitigate mating-induced stresses. Translocation signals located C-terminally or internally conferred substrate recognition by the F system and, remarkably, many substrates also were translocated through heterologous conjugation systems. Our findings highlight the plasticity of conjugation systems in their capacities to co-translocate DNA and many protein substrates.
PubMed: 38940509
DOI: 10.1128/msphere.00354-24 -
Polski Przeglad Chirurgiczny Feb 2024<b><br>Introduction:</b> Ileostomy reversal is a common surgical procedure and currently standardized perioperative and surgical protocols are...
<b><br>Introduction:</b> Ileostomy reversal is a common surgical procedure and currently standardized perioperative and surgical protocols are lacking.</br> <b><br>Aim:</b> LILEO study was designed to perform a multicenter analysis on numerous perioperative parameters and estimation of the incidence of postoperative complications.</br> <b><br>Materials and methods:</b> The study is an open multicenter prospective cohort study. Preliminary results of the LILEO study after 3 months were available from 18 Polish surgical centers comprising full data of 59 patients who underwent ileostomy reversal.</br> <b><br>Results:</b> Parameters such as preoperative care, surgical technique, postoperative course and complications were analyzed. Preoperative fasting was used in 49.1% of patients. Fifty nine percent of anastomosis were handsewn and in 72.9% of patients had primary single suture wound closure. Mean length of hospital stay was 7.9 days (min 2 days, max 26 days). Complications occurred overall in 20 patients (33.9%). In 11.9% of patient's complications had grade III A/B in Clavien-Dindo classification.</br> <b><br>Discussion:</b> The perioperative care in the group of patients undergoing ileostomy reversal still lacks standardized and optimized treatment.</br> <b><br>Conclusions:</b> Ileostomy removal is a procedure with high risk of postoperative complications. Standardization of perioperative care based on further multicenter national study could result in a decrease of complications rate.</br>.
Topics: Humans; Ileostomy; Male; Female; Poland; Prospective Studies; Postoperative Complications; Middle Aged; Adult; Aged; Length of Stay; Reoperation; Treatment Outcome
PubMed: 38940251
DOI: 10.5604/01.3001.0054.2679