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The Kobe Journal of Medical Sciences Jun 2024Olfactory neuroblastoma (ONB) is an uncommon malignant tumor and is usually treated by a multidisciplinary approach includes surgery, radiotherapy, and chemotherapy. A...
Olfactory neuroblastoma (ONB) is an uncommon malignant tumor and is usually treated by a multidisciplinary approach includes surgery, radiotherapy, and chemotherapy. A 62 years-old male had a tumor in the nasal cavity and diagnosed as ONB with Kadish A stage. Anterior skull base surgery was performed as radical treatment. Since the surgical margin was negative, no postoperative radiotherapy was administered. 14 years after the surgery, bilateral otitis media with effusion (OME) was occurred, we found the recurrence tumor at bilateral retropharyngeal lymph node (RPLN) which surrounded the internal carotid arteries. Since these were unresectable, we planned chemoradiotherapy which was 70Gy of intensity modulated radiotherapy combined with two courses of carboplatin and etoposide. The tumor volume was reduced and bilateral OME were improved. He has been alive for 3 years after salvage treatment. Although ONB has a relatively good prognosis, it is known to often cause cervical lymph node metastasis. Grades III and IV of Hyams classification are considered high risk. This case, initial tumor was limited in the nasal cavity and its clinical classification was early stage, but Hyams classification was grade III. In reference to this case, considering that RPLN metastasis are difficult to radically resect at the salvage surgery, including this area in postoperative radiotherapy was considered an option.
Topics: Humans; Male; Esthesioneuroblastoma, Olfactory; Middle Aged; Lymphatic Metastasis; Nose Neoplasms; Nasal Cavity; Skull Base; Neoplasm Recurrence, Local; Chemoradiotherapy
PubMed: 38936878
DOI: 10.24546/0100489917 -
International Journal of Surgery Case... Jun 2024Obturator hernias are rare, occur mainly in slender people and predominantly in females. Underlying pathology of the obturator hernia is a weakening of the obturator...
INTRODUCTION
Obturator hernias are rare, occur mainly in slender people and predominantly in females. Underlying pathology of the obturator hernia is a weakening of the obturator membrane. The obturator hernia is situated between the pubic and ischial bones and is therefore clinically occult. Patients predominantly present with symptoms of bowel obstruction, but can also present with sensory disturbance, leg pain and hip pain. Due to the usually delayed diagnosis, the obturator hernia is associated with increased morbidity and mortality.
CASE PRESENTATION
A 71-year-old female patient with hip pain underwent a protracted diagnostic work-up and was referred to the surgical department by the treating orthopedic surgeon. An incarcerated obturator hernia with a fistula in the adductor ligament was finally diagnosed via CT. The operation included laparoscopic reduction, hernia repair, open small bowel segment resection, local surgical exploration, lavage and antibiotic treatment. The primary hernia repair was performed by direct suture due to the contamination, and a post-primary mesh repair was indicated. However, after complete recovery and no remaining symptoms, the patient refused this despite the indication for definitive laparoscopic hernia repair.
DISCUSSION
Hip pain can have multiple causes. Taking physical characteristics into account can lead to the correct diagnostic pathway. The CT scan revealed the fistula which led to the laparoscopic surgery. Due to the intestinal damage and contamination, the surgical steps were adapted.
CONCLUSION
Obturator hernias should be considered as a reason for atypical symptoms in slender, older patients. Adequate surgical management can be chosen after correct diagnosis.
PubMed: 38936138
DOI: 10.1016/j.ijscr.2024.109945 -
American Society of Clinical Oncology... Jun 2024The landscape of prostate cancer care has rapidly evolved. We have transitioned from the use of conventional imaging, radical surgeries, and single-agent androgen... (Review)
Review
The landscape of prostate cancer care has rapidly evolved. We have transitioned from the use of conventional imaging, radical surgeries, and single-agent androgen deprivation therapy to an era of advanced imaging, precision diagnostics, genomics, and targeted treatment options. Concurrently, the emergence of large language models (LLMs) has dramatically transformed the paradigm for artificial intelligence (AI). This convergence of advancements in prostate cancer management and AI provides a compelling rationale to comprehensively review the current state of AI applications in prostate cancer care. Here, we review the advancements in AI-driven applications across the continuum of the journey of a patient with prostate cancer from early interception to survivorship care. We subsequently discuss the role of AI in prostate cancer drug discovery, clinical trials, and clinical practice guidelines. In the localized disease setting, deep learning models demonstrated impressive performance in detecting and grading prostate cancer using imaging and pathology data. For biochemically recurrent diseases, machine learning approaches are being tested for improved risk stratification and treatment decisions. In advanced prostate cancer, deep learning can potentially improve prognostication and assist in clinical decision making. Furthermore, LLMs are poised to revolutionize information summarization and extraction, clinical trial design and operations, drug development, evidence synthesis, and clinical practice guidelines. Synergistic integration of multimodal data integration and human-AI integration are emerging as a key strategy to unlock the full potential of AI in prostate cancer care.
Topics: Humans; Male; Prostatic Neoplasms; Artificial Intelligence
PubMed: 38935882
DOI: 10.1200/EDBK_438516 -
PloS One 2024Chronic liver diseases are caused by hepatic viral infection, chemicals, and metabolic stress. The protein Grb2-associated binder 1 (Gab1) binds to various growth factor...
Chronic liver diseases are caused by hepatic viral infection, chemicals, and metabolic stress. The protein Grb2-associated binder 1 (Gab1) binds to various growth factor receptors, and triggers cell differentiation/survival signaling pathways. To identify signaling molecules involved in the progression of liver diseases, we performed reverse-phase protein microarray (RPMA)-based screening of hepatocytes isolated from humanized mice after acute HCV infection. Acute viral infection in humanized liver mice significantly decreased the level of hepatocyte p-Gab1. Moreover, hepatoma cells upon HCV infection decreased Gab1 mRNA at later times of infection (D3 to D5) and p-Gab1 level was inversely related to the production of TGF-β. In contrast, the level of p-Gab1 was increased in CCL4-induced fibrotic liver. Hepatoma cells showed elevation of p-Gab1, along with an increase in STAT3 and ERK activation, upon treatment with HGF (ligand of HGF receptor/c-Met) and CCL4. In Gab1 knockdown hepatoma cells, cell proliferative signaling activity was reduced but the level of activated caspase-3 was increased. These findings suggest that hepatocyte Gab1 expression may play a role in promoting liver fibrosis progression by triggering ERK activation and inhibiting apoptosis. It implies that the Gab1-mediated signaling pathway would be a promising therapeutic target to treat chronic liver diseases.
Topics: Animals; Hepatocytes; Liver Cirrhosis; Adaptor Proteins, Signal Transducing; Apoptosis; Signal Transduction; Cell Proliferation; Humans; Mice; Proto-Oncogene Proteins c-met; Hepatocyte Growth Factor; Cell Line, Tumor; Hepatitis C
PubMed: 38935609
DOI: 10.1371/journal.pone.0306345 -
PLoS Biology Jun 2024Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy) leads to an auditory neuropathy called hidden hearing loss (HHL) characterized...
Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy) leads to an auditory neuropathy called hidden hearing loss (HHL) characterized by normal auditory thresholds but reduced amplitude of sound-evoked auditory potentials. It has been proposed that synaptopathy and HHL result in poor performance in challenging hearing tasks despite a normal audiogram. However, this has only been tested in animals after exposure to noise or ototoxic drugs, which can cause deficits beyond synaptopathy. Furthermore, the impact of supernumerary synapses on auditory processing has not been evaluated. Here, we studied mice in which IHC synapse counts were increased or decreased by altering neurotrophin 3 (Ntf3) expression in IHC supporting cells. As we previously showed, postnatal Ntf3 knockdown or overexpression reduces or increases, respectively, IHC synapse density and suprathreshold amplitude of sound-evoked auditory potentials without changing cochlear thresholds. We now show that IHC synapse density does not influence the magnitude of the acoustic startle reflex or its prepulse inhibition. In contrast, gap-prepulse inhibition, a behavioral test for auditory temporal processing, is reduced or enhanced according to Ntf3 expression levels. These results indicate that IHC synaptopathy causes temporal processing deficits predicted in HHL. Furthermore, the improvement in temporal acuity achieved by increasing Ntf3 expression and synapse density suggests a therapeutic strategy for improving hearing in noise for individuals with synaptopathy of various etiologies.
Topics: Animals; Hair Cells, Auditory, Inner; Synapses; Neurotrophin 3; Mice; Auditory Threshold; Evoked Potentials, Auditory; Reflex, Startle; Auditory Perception; Spiral Ganglion; Female; Male; Hearing Loss, Hidden
PubMed: 38935589
DOI: 10.1371/journal.pbio.3002665 -
Indian Journal of Dental Research :... Jan 2024Wet oral environment may have deleterious effects on performance of the composites due to influences of water sorption and solubility. The study evaluated the hydrolytic...
INTRODUCTION
Wet oral environment may have deleterious effects on performance of the composites due to influences of water sorption and solubility. The study evaluated the hydrolytic degradation caused because of water sorption and solubility of silorane and methacrylate-based dental composites.
METHODS
Ten disc samples (2 mm × 10 mm) were prepared. Samples were analyzed for water solubility and sorption according to ISO 4049:2000 regulations and tested for mass gain or loss following immersion in water or in artificial saliva at 1 day, 15 days, and 30 days period. Student's 't' test, repeated measures analysis of variance (ANOVA), and Tukey's post-hoc tests determined statistical significance of the experimental results with global significance set at P = 0.05.
RESULTS
Considerable sorption and solubility was observed with time in both materials on immersion. Silorane composites showed lower water sorption and solubility than methacrylate-based composite (MBC). Artificial saliva demonstrated higher sorption and solubility compared to distilled water.
CONCLUSION
Silorane composites display enhanced hydrolytic stability even after a month of immersion in contrast to conventional methacrylate-based composites (MBCs), making it a better alternative to MBC resins clinically.
Topics: Solubility; Methacrylates; Composite Resins; Water; Silorane Resins; Saliva, Artificial; Materials Testing; Hydrolysis; Dental Materials
PubMed: 38934754
DOI: 10.4103/ijdr.ijdr_195_23 -
Medycyna Pracy Jun 2024Voivodeship Occupational Medicine Centres (VOMC), being higher-level units towards basic units providing preventive care for employees in Poland, play a consultative,...
BACKGROUND
Voivodeship Occupational Medicine Centres (VOMC), being higher-level units towards basic units providing preventive care for employees in Poland, play a consultative, appeal, supervisory and registration role towards them. Additionally, they perform many other tasks specified in the Occupational Medicine Service Act, including conducting diagnostic and jurisprudential activities related to occupational diseases and postgraduate education in occupational medicine.
MATERIAL AND METHODS
The analysis covers data from 2017-2022 on VOMCs activities, derived from mandatory MZ-35 reporting.
RESULTS
Over 6 years, the number of employed physicians at VOMCs decreased from 830 in 2017 to 820 in 2022, with >20% of employment contracts transitioning to other forms of cooperation. The number of employed nurses decreased from 375 to 342, and the number of psychologists from 86 to 82. During the 3 years of the pandemic (2020-2022), compared to 2017-2019, the consultative activity of VOMCs for basic units of occupational health service decreased by nearly 30%, while appeal and supervisory activities decreased by 15.2% and 15.8%, respectively. The number of individuals receiving outpatient medical rehabilitation for occupational pathology decreased by >32%, and the number of services provided for established occupational pathology decreased by >14%. The number of certifications for occupational diseases decreased from 3963 in 2019 to 3518 in the first year of the pandemic, then increased to 4145 in 2021 and 3990 in 2022.
CONCLUSIONS
The COVID-19 pandemic had a significant impact on the functioning of VOMCs. Changes in specific areas of their judicial, consultative, appeal, supervisory, training and rehabilitation activities corresponded with the socio-legal changes observed between 2020-2022. The structure of employment at VOMCs and the scope of their tasks remained stable during the pandemic. The observed changes in employment of medical staff were in line with general trends in healthcare institutions and regional conditions. Med Pr Work Health Saf. 2024;75(4).
PubMed: 38934657
DOI: 10.13075/mp.5893.01502 -
Archivio Italiano Di Urologia,... Jun 2024Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia...
Pentoxifylline treatment as a safe method for selecting viable testicular spermatozoa before cryopreservation of a small numbers of spermatozoa in azoospermia individuals.
BACKGROUND
Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia (NOA). Testicular specimens possess poor motility and low population of viable spermatozoa. Therefore, sperm selection methods such as applying pentoxifylline (PTX) may improve motility in these cases. The main aim of this study was to evaluate the protective effects of PTX on testicular spermatozoa before and after performing SSC.
METHODS
Thirty testicular samples were obtained from men with azoospermia. This study was conducted in two phases. Phase 1 evaluated the effect of PTX for sperm selection before SSC. Twenty testicular samples were divided to two experimental groups: SSC without (I) and with PTX treatment (II). For PTX treatment spermatozoa were incubated with PTX at 37°C for 30 min and only motile spermatozoa were selected for SSC. In phase 2, ten testicular samples were cryopreserved with SSC and warming procedure was carried out in droplet with and without PTX. Motility and viability rates, morphology by motile sperm organelle morphology examination (MSOME), DNA fragmentation by sperm chromatin dispersion test (SCD) and mitochondrial membrane potential (MMP) were evaluated.
RESULTS
In phase 1, post warm motility rate was higher in PTX exposed group compared to the unexposed group (25.6 ± 8.13 vs. 0.85 ± 2.1) (p > 0.00). Recovery rate, viability and morphology were not significantly different between groups. DNA integrity and MMP were also similar between both groups. In phase 2 although motility increased in PTX group compared to without PTX group (29.30 ± 12.73 vs. 1.90 ± 2.64) (p > 0.00), the viability rate was not different (70.40 ± 12.12 vs. 65.30 ± 11.87). All above mentioned parameters were similar between the two SSC groups.
CONCLUSIONS
Supplementation of testicular spermatozoa with PTX before cryopreservation increases motility and did not have adverse effects on viability, morphology, DNA integrity and MMP. PTX could be used as sperm selection method before single sperm cryopreservation, but PTX could not maintain motile the most of viable testicular sperms.
Topics: Male; Humans; Pentoxifylline; Cryopreservation; Azoospermia; Spermatozoa; Sperm Motility; Semen Preservation; DNA Fragmentation; Testis; Adult; Cell Survival; Membrane Potential, Mitochondrial
PubMed: 38934523
DOI: 10.4081/aiua.2024.12525 -
Emerging Microbes & Infections Jun 2024, a group of multi-drug resistant, Gram-positive, aerobic and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the...
, a group of multi-drug resistant, Gram-positive, aerobic and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the pathogenesis of keratitis is largely unknown. To address this, we used New Zealand White rabbits to develop the first eye infection model and conducted tests to study the pathogenesis mechanisms of . There is increasing evidence that biofilms play a significant role in ocular infections, leading us to hypothesize that biofilm formation is crucial for effective infection. In order to look for potential candidate genes which are important in biofilm formation and keratitis. We performed genome sequencing of two ocular isolates, -PW1004 and -PW899, to identify potential virulence factors. Through and studies, we characterized their biological roles in mediating keratitis. Our findings confirmed that is an ocular pathogen by fulfilling the Koch's postulates, and using genome sequence data, we identified encoding a mycolyltransferase, as a crucial gene in biofilm formation and causing keratitis in the rabbit model. This is the first report demonstrating the novel role of mycolyltransferase in causing ocular infections. Overall, our findings contribute to a better understanding of pathogenesis and provide a potential target for treatment. Specific inhibitors targeting TmytC could serve as an effective treatment option for infections.
PubMed: 38934251
DOI: 10.1080/22221751.2024.2373317 -
Haematologica Jun 2024Chromosomal translocations in non-Hodgkin lymphoma (NHL) result in activation of oncogenes by placing them under the regulation of immunoglobulin heavy chain (IGH)...
Chromosomal translocations in non-Hodgkin lymphoma (NHL) result in activation of oncogenes by placing them under the regulation of immunoglobulin heavy chain (IGH) super-enhancers. Aberrant expression of translocated oncogenes induced by enhancer activity can contribute to lymphomagenesis. The role of the IGH enhancers in normal B-cell development is well established, but knowledge regarding the precise mechanisms of their involvement in control of the translocated oncogenes is limited. The goal of this project was to define the critical regions in the IGH regulatory elements and identify enhancer RNAs (eRNA). We designed a sgRNA library densely covering the IGH enhancers and performed tiling CRISPR interference screens in three NHL cell lines. This revealed three regions crucial for NHL cell growth. With chromatin-enriched RNA-Seq we showed transcription from the core enhancer regions and subsequently validated expression of the eRNAs in a panel of NHL cell lines and tissue samples. Inhibition of the essential IGH enhancer regions decreased expression of eRNAs and translocated oncogenes in several NHL cell lines. The observed expression and growth patterns were consistent with the breakpoints in the IGH locus. Moreover, targeting the Eμ enhancer resulted in loss of B-cell receptor expression. In a Burkitt lymphoma cell line, MYC overexpression partially rescued the phenotype induced by IGH enhancer inhibition. Our results indicated the most critical regions in the IGH enhancers and provided new insights into the current understanding of the role of IGH enhancers in B-cell NHL. As such, this study forms a basis for development of potential therapeutic approaches.
PubMed: 38934080
DOI: 10.3324/haematol.2023.284672