Operative strategy for fistula-in-ano without division of the anal sphincter

We would like to thank Mr ER MacDonald for his contribution in data collection during the early years of the study. The material in this paper was presented as a poster at the annual meeting of the American Society of Colon and Rectal Surgeons held in Vancouver, Canada, May 2011.Peer reviewedPublisher PD

Resection of peritoneal metastases causing malignant small bowel obstruction

Background: Resection of peritoneal metastases has been shown to improve survival in patients with abdominal metastatic disease from abdominal or extra abdominal malignancy. This study evaluates the benefit of peritoneal metastatic resection in patients with malignant small bowel obstruction and a past history of treated cancer. Patients and methods: Patients undergoing laparotomy for resection of peritoneal metastases from recurrence of previous cancer between 1992-2003 were reviewed retrospectively. Data were collected about type of primary cancer, interval to recurrence, extent of the disease and completeness of resection, morbidity and mortality and long-term survival. Results: Between 1992 and 2003 there were 79 patients (median age 62, range 19-91) who had laparotomy for small bowel obstruction due to recurrent cancer. The primary cancer was colorectal (31), gynaecologic cancer (19), melanoma (16) and others (13). Overall, the rate of complications was 35% and mortality was 10%. Median survival was 5 months; patients with history of colorectal cancer had better survival than other cancer (median survival 7 months vs. 4 months; p = 0.02). Multivariate analysis showed that the extent of recurrent disease was the only factor that affected overall survival. Conclusion: Laparotomy for small bowel obstruction is a worthwhile option for patients with malignant small bowel obstruction. Although it is associated with significant morbidity and mortality it offers a reasonable survival benefit in particular for patients with completely resectable disease

Delayed-onset heparin-induced thrombocytopenia presenting with multiple arteriovenous thromboses: case report

<p>Abstract</p> <p>Background</p> <p>Delayed-onset heparin-induced thrombocytopenia with thrombosis, albeit rare, is a severe side effect of heparin exposure. It can occur within one month after coronary artery bypass grafting (CABG) with manifestation of different thrombotic events.</p> <p>Case presentation</p> <p>A 59-year-old man presented with weakness, malaise, bilateral lower limb pitting edema and a suspected diagnosis of deep vein thrombosis 18 days after CABG. Heparin infusion was administered as an anticoagulant. Clinical and paraclinical work-up revealed multiple thrombotic events (stroke, renal failure, deep vein thrombosis, large clots in heart chambers) and 48 ×10³/μl platelet count, whereupon heparin-induced thrombocytopenia was suspected. Heparin was discontinued immediately and an alternative anticoagulant agent was administered, as a result of which platelet count recovered. Heparin-induced thrombocytopenia, which causes thrombosis, is a serious side effect of heparin therapy. It is worthy of note that no case of delayed-onset heparin-induced thrombocytopenia with thrombosis associated with cardiopulmonary bypass surgery has thus far been reported in Iran.</p> <p>Conclusion</p> <p>Delayed-onset heparin-induced thrombocytopenia should be suspected in any patient presenting with arterial or venous thromboembolic disorders after recent heparin therapy, even though the heparin exposure dates back to more than a week prior to presentation; and it should be ruled-out before the initiation of heparin therapy.</p

Cold Hardiness and Supercooling Capacity in the Overwintering Larvae of the Codling Moth, Cydia pomonella

The codling moth, Cydia pomonella L. (Lepidoptera: Tortricidae), a worldwide apple pest, is classified as a freeze-intolerant organism and one of the most cold-tolerant pests. The objectives of this study were to examine the supercooling point of overwintering and non-diapausing larvae of C. pomonella as an index of its cold hardiness, and to assess larval mortality following 24 h exposure to extreme low temperatures ranging from -5 to -25°C. The mean (±SE) supercooling point for feeding larvae (third through fifth instars) was -12.4 ± 1.1°C. The mean supercooling point for cocooned, non-diapausing larvae (i.e., non-feeding stages) decreased as the days that the arvae were cocooned increased and changed between -15.1 ± 1.2°C for one to two day cocooned arvae and -19.2 ± 1.8°C for less than five day cocooned larvae. The mean (±SE) supercooling point for other non-feeding stages containing pupae and overwintering larvae were -19.9 ± 1.0°C and -20.2 ± 0.2°C, respectively. Mean supercooling points of C. pomonella larvae were significantly lower during the winter months than the summer months, and sex had no effect on the supercooling point of C. pomonella larvae. The mortality of larvae increased significantly after individuals were exposed to temperatures below the mean supercooling point of the population. The supercooling point was a good predictor of cold hardiness

AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model

Hereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants in AMFR, encoding a RING-H2 finger E3 ubiquitin ligase anchored at the membrane of the endoplasmic reticulum (ER), in two previously genetically unexplained HSP-affected siblings. Subsequently, international collaboration recognized additional HSP-affected individuals with similar bi-allelic truncating AMFR variants, resulting in a cohort of 20 individuals from 8 unrelated, consanguineous families. Variants segregated with a phenotype of mainly pure but also complex HSP consisting of global developmental delay, mild intellectual disability, motor dysfunction, and progressive spasticity. Patient-derived fibroblasts, neural stem cells (NSCs), and in vivo zebrafish modeling were used to investigate pathomechanisms, including initial preclinical therapy assessment. The absence of AMFR disturbs lipid homeostasis, causing lipid droplet accumulation in NSCs and patient-derived fibroblasts which is rescued upon AMFR re-expression. Electron microscopy indicates ER morphology alterations in the absence of AMFR. Similar findings are seen in amfra-/- zebrafish larvae, in addition to altered touch-evoked escape response and defects in motor neuron branching, phenocopying the HSP observed in patients. Interestingly, administration of FDA-approved statins improves touch-evoked escape response and motor neuron branching defects in amfra-/- zebrafish larvae, suggesting potential therapeutic implications. Our genetic and functional studies identify bi-allelic truncating variants in AMFR as a cause of a novel autosomal recessive HSP by altering lipid metabolism, which may potentially be therapeutically modulated using precision medicine with statins

Food industry by-products valorization and new ingredients: cases of study

The concern about food and beverages is gaining importance for the general public in terms of health and more environmentally sustainable food products. Healthy foods imply the awareness on their safety, nutritional characteristics, and the potential inclusion of nutritive complements such as antioxidants, vitamins, and proteins, which promote a benefit to the consumer's health. Also, organic foods, with less added chemicals such as pesticides, are more demanded recently. The environmentally sustainable food production has to reconsider the wastes as by-products that can be transformed to provide valuable compounds (antioxidants, fiber, fuels, etc.) that could be used as new products or raw materials in the food industry or even applied in other sectors such as pharmaceutical, polymer, and energy industries. In this chapter, selected successful case studies in which food wastes are transformed into new products by using different separation and purification technologies will be shown. Furthermore, the use of different wild vegetables from natural environments as a source of valuable compounds and new ingredients will be described.info:eu-repo/semantics/publishedVersio

Notch and Presenilin Regulate Cellular Expansion and Cytokine Secretion but Cannot Instruct Th1/Th2 Fate Acquisition

Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4+ T or reporter cells, the presence of Lunatic Fringe in CD4+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4+ T cells lacking γ-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch) independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation

Notch and Presenilin Regulate Cellular Expansion and Cytokine Secretion but Cannot Instruct Th1/Th2 Fate Acquisition

Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4+ T or reporter cells, the presence of Lunatic Fringe in CD4+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4+ T cells lacking γ-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch) independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation