Laparoscopic cholecystectomy due to acute calculouscholecystitis in 16 weeks' in vitro fertilization and embryo transfer pregnancy: report of the first case

The most common casues of acute abdomen during pregnancy are acute appendicitis followed by acute cholecystitis. The case presented is a 33-year-old patient in 16 weeks' in vitro fertilization and embryo transfer pregnacy who developed acute cholecystitis. Previously there were two unsuccessful cycles, one complicated with ovarian hyperstimulation syndrome. Due to clinical deterioration during intravenous antibiotic therapy laparoscopic cheolecystecomy was performed and acute cholecystitis found. The postoperative course was uneventful. During the first 24 h tocolysis with intravenous fenoterol in addition to peroral atenolol 2 Χ 50 mg was administered. Postoperative course was uneventuful with further normal pregnancy. Elective cesarean section was made in term pregnancy (39 weeks) with singleton with Apgar 10/10. Current guidelines do not recommend prophylactic tocolysis in pregnant population with acute abdomen but there is no mention of the IVF-ET subpopulation of patients. Also, there are no guidelines for thromboprophylaxis in such patients with increased risk of thromboembolic accidents. To our knowledge this is the first case report of a laparoscopic cholecystectomy during IVF-ET gestation

Complex roles of myoglianin in regulating adult performance and lifespan

Myoglianin, the Drosophila homolog of the secreted vertebrate proteins Myostatin and GDF-11, is an important regulator of neuronal modelling, and synapse function and morphology. While Myoglianin suppression during development elicits positive effects on the neuromuscular system, genetic manipulations of myoglianin expression levels have a varied effect on the outcome of performance tests in aging flies. Specifically, Myoglianin preserves jumping ability, has no effect on negative geotaxis, and negatively regulates flight performance in aging flies. In addition, Myoglianin exhibits a tissue-specific effect on longevity, with myoglianin upregulation in glial cells increasing the median lifespan. These findings indicate complex role for this TGF-β-like protein in governing neuromuscular signalling and consequent behavioural outputs and lifespan in adult flies

Potential benefits of medium chain fatty acids in aging and neurodegenerative disease

Neurodegenerative diseases are a large class of neurological disorders characterized by progressive dysfunction and death of neurones. Examples include Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Aging is the primary risk factor for neurodegeneration; individuals over 65 are more likely to suffer from a neurodegenerative disease, with prevalence increasing with age. As the population ages, the social and economic burden caused by these diseases will increase. Therefore, new therapies that address both aging and neurodegeneration are imperative. Ketogenic diets (KDs) are low carbohydrate, high-fat diets developed initially as an alternative treatment for epilepsy. The classic ketogenic diet provides energy via long-chain fatty acids (LCFAs); naturally occurring medium chain fatty acids (MCFAs), on the other hand, are the main components of the medium-chain triglyceride (MCT) ketogenic diet. MCT-based diets are more efficient at generating the ketone bodies that are used as a secondary energy source for neurones and astrocytes. However, ketone levels alone do not closely correlate with improved clinical symptoms. Recent findings suggest an alternative mode of action for the MCFAs, e.g., via improving mitochondrial biogenesis and glutamate receptor inhibition. MCFAs have been linked to the treatment of both aging and neurodegenerative disease via their effects on metabolism. Through action on multiple disease-related pathways, MCFAs are emerging as compounds with notable potential to promote healthy aging and ameliorate neurodegeneration. MCFAs have been shown to stimulate autophagy and restore mitochondrial function, which are found to be disrupted in aging and neurodegeneration. This review aims to provide insight into the metabolic benefits of MCFAs in neurodegenerative disease and healthy aging. We will discuss the use of MCFAs to combat dysregulation of autophagy and mitochondrial function in the context of “normal” aging, Parkinson’s disease, amyotrophic lateral sclerosis and Alzheimer’s disease

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Cytoreductive Surgery (CS) as Treatment of Peritoneal Carcinomatosis: Preliminary Results in Croatia

The purpose of our study was to evaluate initial results following introduction of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Cytoreductive Surgery (CS). Twenty two patients with intraperitoneal malignancy undergone cytoreductive surgery (CS) and hyperthermic intraoperative chemotherapy (HIPEC) between January of 2007 and January 2010. Nine patients had adenocarcinoma of colorectal origin, 8 patients had ovarian cancer, and 5 had pseudomyxoma peritonei. Inclusion criteria were diagnosis of peritoneal carcinomatosis based on intraoperative assessment during first operative procedure for intraabdominal malignancy or follow-up diagnostic imaging proof. Excluded were patients with known malignant proliferation outside abdomen, liver metastasis and ASA score 4 and higher. All patients with pseudomyxoma peritonei diagnosis are alive, with mean follow-up time 24.8 months (range 15–35). In group of patients with adenocarcinoma from colorectal origin, 3 died, resulting in mean survival time 7.6 months (range 1–16). In group of patients with ovarian cancer, 2 died, resulting in mean survival time 13.8 months (range 0–31). Two patients died in early postoperative period. Most of the patients had some sort of mental disorder. Although HIPEC with CS improves survival, during introduction period higher morbidity and mortality could be expected

Plum modulates Myoglianin and regulates synaptic function in D. melanogaster

Alterations in the neuromuscular system underlie several neuromuscular diseases and play critical roles in the development of sarcopenia, the age-related loss of muscle mass and function. Mammalian Myostatin (MST) and GDF11, members of the TGF-β superfamily of growth factors, are powerful regulators of muscle size in both model organisms and humans. Myoglianin (MYO), the Drosophila homologue of MST and GDF11, is a strong inhibitor of synaptic function and structure at the neuromuscular junction in flies. Here, we identified Plum, a transmembrane cell surface protein, as a modulator of MYO function in the larval neuromuscular system. Reduction of Plum in the larval body-wall muscles abolishes the previously demonstrated positive effect of attenuated MYO signalling on both muscle size and neuromuscular junction structure and function. In addition, downregulation of Plum on its own results in decreased synaptic strength and body weight, classifying Plum as a (novel) regulator of neuromuscular function and body (muscle) size. These findings offer new insights into possible regulatory mechanisms behind ageing- and disease-related neuromuscular dysfunctions in humans and identify potential targets for therapeutic interventions

Hemoptysis as an Early Symptom of Abdominal Actinomycosis with Thoracic Extension Ten Years after Cholecystectomy with Retained Gallstone

Abstract Background: Thoracoabdominal actinomycosis is rare, especially in the context of readily available medical facilities. Methods: Case report and review of the literature. Case Report: A 54-year-old male patient was admitted because of hemoptysis and a pulmonary infiltrate in the left lower lobe. His history was unremarkable except for chronic gastritis and an elective laparoscopic cholecystectomy performed 10 years earlier. Following persistent hemoptysis, elevated inflammatory markers, and a non-revealing bronchoscopy, a computed tomography scan of the thorax and upper abdomen revealed a tumor in the upper part of the left kidney spreading directly to the adjacent diaphragm and left lower lobe. Laparotomy revealed a granulomatous mass containing a gallstone, as well as orange granular content. The treatment involved surgical removal of the mass, splenectomy, excision of the infiltrated part of the left hemidiaphragm, and decortication of the left lower lobe. Because of a prolonged post-operative low-grade fever and radiologically confirmed encapsulation in the lingula, the patient was given ceftriaxone. Repeat bronchoscopy revealed Actinomyces meyeri. The initial antibiotic therapy was replaced with amoxicillin-clavulanic acid, after which the patient's health improved. Conclusion: Actinomycosis is still a highly intriguing disease, as initial symptoms often mislead clinicians. It is important to consider the disease whenever we are challenged diagnostically or when risk factors are present

Medium-Chain Fatty Acids Rescue Motor Function and Neuromuscular Junction Degeneration in a Drosophila Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterised by progressive degeneration of the motor neurones. An expanded GGGGCC (G4C2) hexanucleotide repeat in C9orf72 is the most common genetic cause of ALS and frontotemporal dementia (FTD); therefore, the resulting disease is known as C9ALS/FTD. Here, we employ a Drosophila melanogaster model of C9ALS/FTD (C9 model) to investigate a role for specific medium-chain fatty acids (MCFAs) in reversing pathogenic outcomes. Drosophila larvae overexpressing the ALS-associated dipeptide repeats (DPRs) in the nervous system exhibit reduced motor function and neuromuscular junction (NMJ) defects. We show that two MCFAs, nonanoic acid (NA) and 4-methyloctanoic acid (4-MOA), can ameliorate impaired motor function in C9 larvae and improve NMJ degeneration, although their mechanisms of action are not identical. NA modified postsynaptic glutamate receptor density, whereas 4-MOA restored defects in the presynaptic vesicular release. We also demonstrate the effects of NA and 4-MOA on metabolism in C9 larvae and implicate various metabolic pathways as dysregulated in our ALS model. Our findings pave the way to identifying novel therapeutic targets and potential treatments for ALS

Deletion of endogenous Tau proteins is not detrimental in Drosophila

Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions

Surgical treatment of perihilar cholangiocarcinoma: 10-year experience at a single institution

Background: Our study evaluates surgical outcomes of patients treated for perihilar cholangiocarcinoma in a single institution and demonstrates postoperative (90 days) morbidity and mortality rates and potential prognostic factors associated with complications. Methods: Medical records of all patients with a diagnosis of perihilar cholangiocarcinoma (pCC) between 2007 and 2017 who underwent a surgical procedure at the University hospital centre Zagreb, were retrospectively evaluated. Statistical analysis to determine predictors of postoperative mortality was performed using the Chi-square test and Fisher exact probability test where appropriate. Results: Out of 52 surgically treated patients, 43 underwent radical and 9 palliative procedures. Hilar resection and hilar resection along with right hepatectomy were the most commonly performed procedures in 34 radically treated patients. Overall morbidity and mortality rates were 46% and 5.7%, respectively. Significantly higher morbidity rate was observed in a group of patient with untreated preoperative jaundice and in those aged 70 and over. Conclusion: Current guidelines favor extension of radicality in treatment of pCC by performing left or right hepatectomy in addition to hilar resection. This may increase R0 resection rates and prolong disease free survival. Our experience shows similar mortality/morbidity rates as reported in other centers and confirms that in selected patients, concomitant hepatectomy for perihilar pCC is a safe and feasible surgical strategy