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1.
Article in English | MEDLINE | ID: mdl-38808314

ABSTRACT

A 68-year-old man was admitted with hematochezia. Emergency computed tomography showed multiple diverticula throughout the colon. Initial colonoscopy on day 2 showed no active bleeding, but massive hematochezia on day 3 led to the performance of an emergency endoscopy. Substantial bleeding in the ileocecal area obscured the visual field, making it challenging to view the area around the bleeding site. Two endoscopic band ligations (EBLs) were applied at the suspected bleeding sites. Hemostasis was achieved without active bleeding after EBL. However, the patient developed lower right abdominal pain and fever (39.4°C) on day 6. Urgent computed tomography revealed appendiceal inflammation, necessitating emergency open ileocecal resection for acute appendicitis. Pathological examination confirmed acute phlegmonous appendicitis, with EBLs noted at the appendiceal orifice and on the anal side. This case illustrates the efficacy of EBL in managing colonic diverticular bleeding. However, it also highlights the risk of appendicitis due to EBL in cases of ileocecal hemorrhage exacerbated by poor visibility due to substantial bleeding. Endoscopists need to consider this rare but important complication when performing EBL in similar situations.

2.
World J Gastrointest Surg ; 16(6): 1521-1526, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983361

ABSTRACT

In colon cancer surgery, ensuring the complete removal of the primary tumor and draining lymph nodes is crucial. Lymphatic drainage in the colon follows the vascular supply, typically progressing from pericolic to paraaortic lymph nodes. While NCCN guidelines recommend the removal of 10-12 lymph nodes for adequate oncological resection, achieving complete oncological resection involves more than just meeting these numerical targets. Various techniques have been developed and studied over time to attain optimal oncological outcomes. A key technique central to this goal is identifying the ileocolic vessels at their origin from the superior mesenteric vessels. Complete excision of the visceral and parietal mesocolon ensures the intact removal of the specimen, while D3 lymphadenectomy targets all draining regional lymph nodes. Although these principles emphasize different aspects, they ultimately converge to achieve the same goal of complete oncological resection. This article aims to simplify the surgical steps that align with the principle of central vascular ligation and mesocolon mobilization while ensuring adequate D3 dissection.

3.
World J Clin Cases ; 12(18): 3567-3574, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38983412

ABSTRACT

BACKGROUND: Superior mesenteric artery (SMA) injuries rarely occur during blunt abdominal injuries, with an incidence of < 1%. The clinical manifestations mainly include abdominal hemorrhage and peritoneal irritation, which progress rapidly and are easily misdiagnosed. Quick and accurate diagnosis and timely effective treatment are greatly significant in managing emergent cases. This report describes emergency rescue by a multidisciplinary team of a patient with hemorrhagic shock caused by SMA rupture. CASE SUMMARY: A 55-year-old man with hemorrhagic shock presented with SMA rupture. On admission, he showed extremely unstable vital signs and was unconscious with a laceration on his head, heart rate of 143 beats/min, shallow and fast breathing (frequency > 35 beats/min), and blood pressure as low as 20/10 mmHg (1 mmHg = 0.133 kPa). Computed tomography revealed abdominal and pelvic hematocele effusion, suggesting active bleeding. The patient was suspected of partial rupture of the distal SMA branch. The patient underwent emergency mesenteric artery ligation, scalp suture, and liver laceration closure. In view of conditions with acute onset, rapid progression, and high bleeding volume, key points of nursing were conducted, including activating emergency protocol, opening of the green channel, and arranging relevant examinations with various medical staff for quick diagnosis. The seamless collaboration of the multidisciplinary team helped shorten the preoperative preparation time. Emergency laparotomy exploration and mesenteric artery ligation were performed to mitigate hemorrhagic shock while establishing efficient venous accesses and closely monitoring the patient's condition to ensure hemodynamic stability. Strict measures were taken to avoid intraoperative hypothermia and infection. CONCLUSION: After 3.5 h of emergency rescue and medical care, bleeding was successfully controlled, and the patient's condition was stabilized. Subsequently, the patient was transferred to the intensive care unit for continuous monitoring and treatment. On the sixth day, the patient was weaned off the ventilator, extubated, and relocated to a specialized ward. Through diligent medical intervention and attentive nursing, the patient made a full recovery and was discharged on day 22. The follow-up visit confirmed the patient's successful recovery.

4.
Front Cell Dev Biol ; 12: 1399934, 2024.
Article in English | MEDLINE | ID: mdl-38983787

ABSTRACT

Sialadenitis and sialadenitis-induced sialopathy are typically caused by obstruction of the salivary gland ducts. Atrophy of the salivary glands in experimental animals caused by duct ligation exhibits a histopathology similar to that of salivary gland sialadenitis. Therefore, a variety of duct ligation/de-ligation models have been commonly employed to study salivary gland injury and regeneration. Duct ligation is mainly characterised by apoptosis and activation of different signaling pathways in parenchymal cells, which eventually leads to gland atrophy and progressive dysfunction. By contrast, duct de-ligation can initiate the recovery of gland structure and function by regenerating the secretory tissue. This review summarizes the animal duct ligation/de-ligation models that have been used for the examination of pathological fundamentals in salivary disorders, in order to unravel the pathological changes and underlying mechanisms involved in salivary gland injury and regeneration. These experimental models have contributed to developing effective and curative strategies for gland dysfunction and providing plausible solutions for overcoming salivary disorders.

5.
Dig Endosc ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965645

ABSTRACT

OBJECTIVES: The hemostatic mechanism of endoscopic detachable snare ligation (EDSL) for colonic diverticular hemorrhage (CDH) is similar to that of endoscopic band ligation, which is effective and safe. However, because reports on EDSL are scarce, we conducted a two-center cohort study to evaluate its effectiveness. METHODS: This study analyzed 283 patients with CDH treated with EDSL at two Japanese hospitals between July 2015 and November 2021. Patient characteristics and clinical outcomes were retrospectively evaluated. A Kaplan-Meier analysis was performed to evaluate the cumulative probability of rebleeding after EDSL. A Cox proportional hazards regression analysis was performed to compare the effects of complete and incomplete ligation on rebleeding. RESULTS: The initial hemostasis success and early rebleeding rates were 97.9% and 11.0%, respectively. The time to hemostasis after identification of the bleeding site and total procedure time were 9 min and 44 min, respectively. Red blood cell transfusion was required for 32.9% of patients. The median hospital length of stay after EDSL was 5 days. The complete ligation rate of the early rebleeding group was significantly lower than that of the group without early rebleeding (P < 0.01). The 1-year cumulative rebleeding rate with EDSL was 28.2%. Complete ligation was associated with decreased cumulative rebleeding after EDSL (P < 0.01). One patient experienced colonic diverticulitis; however, colonic perforation was not observed. CONCLUSION: Complete ligation is associated with reduced short-term and long-term rebleeding. EDSL could be valuable for CDH because of its low rebleeding rate and the absence of serious adverse events.

6.
Chembiochem ; : e202400253, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38965889

ABSTRACT

The chemical rules governing protein folding have intrigued generations of researchers for decades. With the advent of artificial intelligence (AI), prediction of protein structure has improved tremendously. However, there is still a level of analysis that is only possible through wet laboratory experiments, especially in respect to the investigation of the pathological effect of mutations and posttranslational modifications (PTMs) on proteins of interest. This requires the availability of pure peptides and proteins in sufficient quantities for biophysical, biochemical, and functional studies. In this context, chemical protein synthesis and semi-synthesis are powerful tools in protein research, which help to enlighten the role of protein modification in the physiology and pathology of proteins. A protein of high interest in the field of biomedicine is alpha-synuclein (aSyn), a protein deeply associated with several devastating neurodegenerative disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), or multiple systems atrophy (MSA). Here, we describe several methods and pathways to synthesize native or modified aSyn, and discuss how these approaches enable us to address pathological mechanisms that may open novel perspectives for therapeutic intervention.

7.
Cureus ; 16(6): e61858, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975487

ABSTRACT

Pseudoaneurysms of the right hepatic artery following cholecystectomy are caused by either vascular damage or erosion after a biliary leak. Symptoms often include haemobilia, melena, vomiting, jaundice, and hemodynamic failure due to aneurysm rupture. The ideal treatment is arterial embolization or, in rare cases, stenting. We present a case of pseudoaneurysm of the right hepatic artery post-laparoscopic cholecystectomy. The patient presented with abdominal pain, vomiting, and hemodynamic failure on postoperative day 45. Magnetic resonance imaging (MRI) showed a large hematoma and a pseudoaneurysm of the right hepatic artery. A laparotomy was performed, and a large hematoma was found and evacuated. After the pringle maneuver, the pseudoaneurysm was resected. The right hepatic artery was ligated with clips, and a sub-hepatic drain was placed. The non-availability of emergency embolization forced surgical closure of the right hepatic artery, which is still the first-line treatment for such cases. Injury of the right hepatic artery is a rare complication, often overlooked by surgeons, and requires early diagnosis. Surgical treatment is reserved for cases of embolization failure or hemodynamic instability.

8.
J Transl Med ; 22(1): 644, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982507

ABSTRACT

BACKGROUND: Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent-offspring trios and proband only analysis. METHODS: We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. RESULTS: Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. CONCLUSION: CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.


Subject(s)
DNA Copy Number Variations , Exome Sequencing , Genetic Diseases, Inborn , Humans , DNA Copy Number Variations/genetics , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Reproducibility of Results , Female , Predictive Value of Tests , Male , Retrospective Studies
9.
Tech Coloproctol ; 28(1): 78, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955875

ABSTRACT

BACKGROUND: Laser hemorrhoidoplasty has demonstrated significant therapeutic effectiveness. To diminish postoperative bleeding and enhance overall outcomes, we have additionally adopted suture ligating the feeding vessels. This study aimed to understand the treatment outcomes and any associated complications. METHODS: This study comprised patients with symptomatic grade II-III hemorrhoids who underwent laser hemorrhoidoplasty with feeding vessel suture ligation and Milligan-Morgan hemorrhoidectomy between 1 September 2020, and 31 August 2022. Surgical-related details, postoperative pain, discomfort after discharge, hemorrhoid recurrence, and any complications were collected from inpatient records, outpatient follow-ups, and telephone interviews. Initially, we will analyze the distinctions between the laser group and the traditional group, followed by an investigation into complications and satisfaction within the laser surgery subgroup. RESULTS: The study included 323 patients, with 173 undergoing laser hemorrhoidoplasty (LHP) and 150 undergoing Milligan-Morgan hemorrhoidectomy. Regarding pain assessment, the LHP group exhibited superior performance compared to traditional surgery at postoperative 4 h, before discharge, and during the first and second outpatient visits, with statistically significant differences. Additionally, the LHP group had a lower rate of urinary retention and experienced significantly less pain, with statistically significant differences. CONCLUSIONS: Laser hemorrhoidoplasty with feeding vessels suture ligation has been shown to reduce postoperative pain and appears to be a promising minimally invasive treatment option for symptomatic grade II and III hemorrhoids.


Subject(s)
Hemorrhoidectomy , Hemorrhoids , Laser Therapy , Pain, Postoperative , Suture Techniques , Humans , Hemorrhoids/surgery , Ligation/methods , Female , Retrospective Studies , Male , Hemorrhoidectomy/methods , Hemorrhoidectomy/adverse effects , Middle Aged , Treatment Outcome , Adult , Pain, Postoperative/etiology , Laser Therapy/methods , Aged , Recurrence , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Patient Satisfaction , Sutures
10.
Synlett ; 35(2): 145-154, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38947226

ABSTRACT

Enamine N-oxides act as a chemical linchpin bridging two bioorthogonal associative and dissociative reactions. This article describes the design of enamine N-oxides; their synthesis through the retro-Cope elimination reaction; the use of solvent, hyperconjugation, strain, and rehybridization effects to achieve bioorthogonal reactivity; and their rapid reductive cleavage with diboron reagents. The coordinated assembly and disassembly of the enamine N-oxide motif constitutes a powerful chemical operation that enables the attachment and detachment of small molecules from biomacromolecules in a biological setting.

11.
Res Vet Sci ; 176: 105343, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38970869

ABSTRACT

Cholestasis is a hepatic disease reported in humans, dogs, and chickens and is characterized by various signs. Bile duct ligation (BDL) is a standard model for research in cholestasis in male rats and mice. However, the timing and degree of structural changes in BDL-subjected liver differ in the two animal species. This study focused on chickens as a choice model for cholestasis. Specifically, we aimed to evaluate the features of BDL in hens and compare them with those in rats and mice. Eighteen hens, 19 female ICR mice, and 18 female SD rats were randomly divided into the sham-operated and BDL groups. At 2, 4, and 6 weeks after BDL, and 4 weeks after the sham operation, liver and blood samples were collected and analyzed histologically and biochemically. Histologically, bile duct proliferation in BDL-subjected livers was first observed in the chickens and then the rats and mice, whereas CD44-positive small hepatocytes were observed only in chickens in the BDL group. Biochemically, the mRNA expression of the hepatocyte growth factor was higher in BDL-subjected chickens, while Interleukin 6 expression was higher in the BDL-subjected rats and mice than in animals in the sham group. In addition, farnesoid X receptor mRNA expression was lower in the BDL-subjected chickens than in the sham chickens. The BDL group had significantly higher total bile acid blood concentration than the sham group. In conclusion, the signs of hepatopathy caused by BDL differ among animal species. Furthermore, we propose that compared to BDL-subjected mice and rats, BDL-subjected chickens are a novel cholestasis animal model that demonstrates severe hepatopathy and liver restructuring.

12.
Biosens Bioelectron ; 262: 116551, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971039

ABSTRACT

Controllable assembly of DNA nanostructure provides a powerful way for quantitative analysis of various targets including nucleic acid molecules. In this study, we have designed detachable DNA nanostructures at electrochemical sensing interface and constructed a ligation chain reaction (LCR) strategy for amplified detection of miRNA. A three-dimensional DNA triangular prism nanostructure is fabricated to provide suitable molecule recognition environment, which can be further regenerated for additional tests via convenient pH adjustment. Target triggered LCR is highly efficient and specific towards target miRNA. Under optimal experimental conditions, this approach enables ultrasensitive exploration in a wide linear range with a single-base resolution. Moreover, it shows excellent performances for the analysis of cell samples and clinical serum samples.

13.
Sci Rep ; 14(1): 15389, 2024 07 04.
Article in English | MEDLINE | ID: mdl-38965256

ABSTRACT

The objective was to explore the efficacy of single-port laparoscopic percutaneous extraperitoneal closure using double-modified hernia needles with hydrodissection (SLPEC group) and two-port laparoscopic percutaneous extraperitoneal closure (TLPEC group) for the treatment of giant indirect inguinal hernias in children. We performed a retrospective review of all children with giant indirect inguinal hernias (inner ring orifice diameter ≥ 1.5 cm) who underwent laparoscopic high ligation of the hernia sac at FuJian Children's Hospital from January 2019 to December 2021. We collected data from the medical records of all the children and analysed their clinical characteristics and operation-related and follow-up information. Overall, this study included a cohort of 219 patients with isolated giant inguinal hernias who had complete clinical data and who had undergone laparoscopic high ligation of the hernia sac at our centre. All procedures were successfully performed for the 106 patients who underwent SLPEC and for the 113 patients who underwent TLPEC at our centre. There were no statistically significant differences in patient age, sex, body weight, follow-up time or the side of inguinal hernia between the SLPEC group and the TLPEC group (P = 0.123, 0.613, 0.121, 0.076 and 0.081, respectively). However, there were significant differences in the bleeding volume, visual analogue scale (VAS) score, and postoperative activity time between the two groups (P ≤ 0.001). The operation times in the TLPEC group were significantly longer than those in the SLPEC group (P = 0.048), but there were no significant differences in hospital length of stay or hospitalization costs between the two groups (P = 0.244 and 0.073, respectively). Incision scars were found in 2 patients in the SLPEC group and 9 patients in the TLPEC group, and there was a significant difference between the two groups (P = 0.04). However, the incidence of ipsilateral hernia recurrence, surgical site infection, suture-knot reactions and chronic inguinodynia did not significantly differ between the two groups (P = 0.332, 0.301, 0.332 and 0.599, respectively). Postoperative hydrocele occurred in only 1 male child in the SLPEC group and in no male children in the TLPEC group, and there was no difference between the two groups (P = 0.310). In this study, there were no cases of testicular atrophy or iatrogenic ascent of the testis. Compared with the TLPEC group, the SLPEC group had the advantages of a concealed incision, light scarring, minimal invasiveness, a reduced operation time, minimal bleeding, mild pain and rapid recovery. In conclusion, SLPEC using double-modified hernia needles with hydrodissection and high ligation of the hernia sac is a safe, effective and minimally invasive surgery. The cosmetic results are impressive, and the follow-up results are promising.


Subject(s)
Hernia, Inguinal , Herniorrhaphy , Laparoscopy , Humans , Hernia, Inguinal/surgery , Male , Laparoscopy/methods , Female , Retrospective Studies , Child, Preschool , Child , Herniorrhaphy/methods , Herniorrhaphy/instrumentation , Needles , Infant , Treatment Outcome , Postoperative Complications/epidemiology , Postoperative Complications/etiology
14.
Front Pharmacol ; 15: 1374179, 2024.
Article in English | MEDLINE | ID: mdl-38904004

ABSTRACT

Ethnopharmacological relevance: G. uralensis Fisch. (Glycyrrhiza uralensis) is an ancient and widely used traditional Chinese medicine with good efficacy in clearing heat and detoxifying action. Studies suggest that Glycyrrhiza Uralensis Polysaccharides (GUP), one of the major components of G. uralensis, has anti-inflammatory, anti-cancer and hepatoprotective effects., but its exact molecular mechanism has not been explored in depth. Aim of the study: Objectives of our research are about exploring the anti-inflammatory role of GUP and the mechanisms of its action. Materials and methods: ELISA kits, Western blotting, immunofluorescence, quantitative real-time PCR, immunoprecipitation and DMXAA-mediated STING activation mice models were performed to investigate the role of GUP on the cGAS-STING pathway. To determine the anti-inflammatory effects of GUP, cecal ligation and puncture (CLP) sepsis models were employed. Results: GUP could effectively inhibit the activation of the cGAS-STING signaling pathway accompany by a decrease the expression of type I interferon-related genes and inflammatory factors in BMDMs, THP-1, and human PBMCs. Mechanistically, GUP does not affect the oligomerization of STING, but affects the interaction of STING with TBK1 and TBK1 with IRF3. Significantly, GUP had great therapeutic effects on DMXAA-induced agonist experiments in vivo as well as CLP sepsis in mice. Conclusion: Our studies suggest that GUP is an effective inhibitor of the cGAS-STING pathway, which may be a potential medicine for the treatment of inflammatory diseases mediated by the cGAS-STING pathway.

15.
Bioorg Chem ; 150: 107549, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38896934

ABSTRACT

Protein semisynthesis approaches are key for gaining insights into the effects of post-translational modifications (PTMs) on the structure and function of modified proteins. Among PTMs, ubiquitination involves the conjugation of a small protein modifier to a substrate amino acid residue and is unique in controlling a variety of cellular processes. Interest has grown in understanding the role of ubiquitination in neurodegenerative conditions, including tauopathies. The latter are characterized by the accumulation of the intrinsically disordered protein tau in the form of neurofibrillary tangles in the brains of patients. The presence of ubiquitinated tau in the pathological aggregates suggests that ubiquitination might play a role in the formation of abnormal protein deposits. In this study, we developed a new strategy, based on dehydroalanine chemistry, to install wild type ubiquitin on a tau repeat domain construct with site-specificity. We optimized a three-step reaction which yielded a good amount of highly pure tau repeat domain ubiquitinated in position 353. The structural features of the conjugate were examined by circular dichroism and NMR spectroscopy. The ubiquitinated tau was challenged in a number of assays: fibrils formation under aggregating conditions in vitro, chemical stability upon exposure to a variety of biological media including cell extracts, and internalization into astrocytes. The results demonstrated the wide applicability of the new semisynthetic strategy for the investigation of ubiquitinated substrates in vitro or in cell, and in particular for studying if ubiquitination has a role in the molecular mechanisms that underlie the aberrant transition of tau into pathological aggregates.

16.
Methods Enzymol ; 698: 169-194, 2024.
Article in English | MEDLINE | ID: mdl-38886031

ABSTRACT

Peptide ligation chemistries have revolutionized the synthesis of proteins with site-specific modifications or proteomimetics through assembly of multiple peptide segments. In order to prepare polypeptide chains consisting of 100-150 amino acid residues or larger generally assembled from three or more peptide segments, iterative purification process that decreases the product yield is usually demanded. Accordingly, methodologies for one-pot peptide ligation that omit the purification steps of intermediate peptide segments have been vigorously developed so far to improve the efficiency of chemical protein synthesis. In this chapter, we first outline the concept and recent advances of one-pot peptide ligation strategies. Then, the practical guideline for the preparation of peptide segments for one-pot peptide ligation is described with an emphasis on diketopiperazine thioester synthesis. Finally, we disclose the explicit protocols for one-pot four segment ligation via repetitive deprotection of N-terminal thiazolidine by a 2-aminobenzamide type aldehyde scavenger.


Subject(s)
Peptides , Thiazolidines , Thiazolidines/chemistry , Peptides/chemistry , Diketopiperazines/chemistry
17.
Am J Epidemiol ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38896053

ABSTRACT

Ovarian cancer incidence has declined in recent decades, due in part to oral contraceptive (OC) use and tubal ligation. However, intrauterine device (IUD) use has increasingly replaced OC use. As ovarian cancer is an inflammation-related disease, we examined the association of OC use, IUD use, and tubal ligation with plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor α receptor 2 (sTNFR2), in the Nurses' Health Study (NHS) and NHSII. After adjusting for reproductive, hormonal, and lifestyle factors, and mutual adjustment for other methods of contraception, there were no differences in inflammatory markers between ever and never use of each method. However, CRP levels decreased from an average 30.4% (-53.6, 4.4) with every 5 years since initial IUD use (P-trend=0.03), while CRP increased an average 9.9% (95% CI: 5.7, 14.3) with every 5 years of use of OC (P-trend<0.0001) as well as differences by BMI and menopausal status. Our results suggest IUD use and tubal ligation are not associated with higher circulating inflammatory markers long term, although long duration of OC use may increase generalized inflammation, which may in part explain why its protective effect wanes over time.

18.
World J Gastroenterol ; 30(21): 2827-2828, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38899333

ABSTRACT

The combination of endoscopic ultrasound with endoscopic treatment of type 1 gastric variceal hemorrhage may improve the robustness and generalizability of the findings in future studies. Moreover, the esophageal varices should also be included in the evaluation of treatment efficacy in subsequent studies to reach a more convincing conclusion.


Subject(s)
Endosonography , Esophageal and Gastric Varices , Gastrointestinal Hemorrhage , Tissue Adhesives , Esophageal and Gastric Varices/therapy , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/surgery , Esophageal and Gastric Varices/diagnosis , Humans , Ligation/methods , Treatment Outcome , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Gastrointestinal Hemorrhage/surgery , Tissue Adhesives/administration & dosage , Endosonography/methods , Injections , Hemostasis, Endoscopic/methods , Endoscopy, Gastrointestinal/methods
19.
Neurogenetics ; 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38850354

ABSTRACT

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive allelic muscle diseases caused by dystrophin gene mutations. Eight hundred thirty-seven patients admitted between 1997 and 2022 were included in the study. Two hundred twenty patients were analyzed by multiplex PCR (mPCR) alone. Five hundred ninety-five patients were investigated by multiplex ligation-dependent probe amplification (MLPA), and 54 patients were examined by sequencing. Deletion was detected in 60% (132/220) of the cases in the mPCR group only and in 58.3% (347/595) of the cases with MLPA analysis. The rates of deletion and duplication were 87.7% and 12.3%, respectively, in the MLPA analysis. Single exon deletions were the most common mutation type. The introns 43-55 (81.8%) and exons 2-21 (13.1%) regions were detected as hot spots in deletions. It was determined that 89% of the mutations were suitable for exon skipping therapy. The reading frame rule did not hold in 7.6% of D/BMD cases (17/224). We detected twenty-five pathogenic/likely pathogenic variants in sequencing, five of which were novel variants. Nonsense mutation was the most common small mutation (44%). 21% of DMD patients were familial. We detected germline mosaicism in four families (4.3%) in the large rearrangement group and one gonosomal mosaicism in a family with a nonsense mutation. This is the largest study examining genotype and phenotype data in Turkish D/BMD families investigated by MLPA analysis. The reading frame hypothesis is not valid in all cases. Sharing the genotype and phenotype characteristics of these cases in the literature will shed light on the molecular structure of DMD and guide gene therapy research. In genetic counseling, carrier screening in the family and possible gonadal mosaicism should be emphasized.

20.
Physiol Rep ; 12(11): e16002, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38831632

ABSTRACT

During skeletal muscle development, the intricate mitochondrial network formation relies on continuous fission and fusion. This process in larger mammals differs from rodents, the most used animal models. However, the expression pattern of proteins regulating mitochondrial dynamics in developing skeletal muscle remains unexplored in larger mammals. Therefore, we characterized the cellular expression and tissue-level distribution of these proteins during development taking goat as a model. We have performed histological and immunohistochemical analyses to study metabolic features in various muscles. Neonatal muscles display uniform distribution of mitochondrial activity. In contrast, adult muscles exhibit clear distinctions based on their function, whether dedicated for posture maintenance or facilitating locomotion. Mitochondrial fission proteins like DRP-1, MFF, and fusion proteins like MFN-1 and 2 are abundantly expressed in neonatal muscles. Fission proteins exhibit drastic downregulation with limited peripheral expression, whereas fusion proteins continue to express in a fiber-specific manner during adulthood. Locomotory muscles exhibit different fibers based on mitochondrial activity and peripheralization with high SDH activity. The proximity ligation assay between MFN1 and MFN2 demonstrates that their interaction is restricted to subsarcolemmal mitochondria in adult fibers while distributed evenly in neonatal fibers. These differences between postural and locomotory muscles suggest their physiological and metabolic properties are different.


Subject(s)
Goats , Mitochondrial Dynamics , Mitochondrial Proteins , Muscle, Skeletal , Animals , Goats/metabolism , Mitochondrial Dynamics/physiology , Muscle, Skeletal/metabolism , Muscle, Skeletal/growth & development , Muscle, Skeletal/physiology , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Mitochondria, Muscle/metabolism , Muscle Development/physiology
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