Unusual cause of a painful right testicle in a 16-year-old man: a case report

<p>Abstract</p> <p>Introduction</p> <p>Urgent surgical exploration of the scrotum of a child or teenager who presents with a painful and swollen testicle is paramount if testicular torsion is not to be missed. It is extremely rare for a non-scrotal pathology to present with acute scrotal signs. Here we present such a rare case and emphasize the importance of being aware of this potential clinical pitfall.</p> <p>Case presentation</p> <p>A 16-year-old Caucasian man presented as a surgical emergency with a five to six hour history of a painful, red, and swollen right hemiscrotum. He also complained of vague lower abdominal pain, vomiting, and watery diarrhea. He had a temperature of 38.5°C and a tender, red, and swollen right hemiscrotum. The right testicle appeared elevated. He was mildly tender in his central and upper abdomen and less so in the lower abdomen. No convincing localizing abdominal signs were noted. He had an increased white cell count (15 × 10⁹/L) and C-reactive protein (CRP; 300 mg/L). Urgent right hemiscrotal exploration revealed about 5 ml of pus in the tunica vaginalis and a normal testicle. A right iliac fossa incision identified the cause: a perforated retrocecal appendix. Appendectomy was performed, and both the abdomen and scrotum washed copiously with saline before closure. The patient made an uneventful recovery.</p> <p>Conclusion</p> <p>Acute appendicitis presenting with scrotal signs due to a patent processus vaginalis is an extremely rare clinical entity. To date, fewer than five such cases have been reported in the medical literature. It is, therefore, extremely important to be aware of this unusual clinical scenario, as only a high index of suspicion will enable prompt, successful management of both the appendicitis and the scrotal abscess.</p

Activity Dependent Protein Degradation Is Critical for the Formation and Stability of Fear Memory in the Amygdala

Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradation-specific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

In silico Identification and Expression of Protocadherin Gene Family in Octopus vulgaris

Connecting millions of neurons to create a functional neural circuit is a daunting challenge. Vertebrates developed a molecular system at the cell membrane to allow neurons to recognize each other by distinguishing self from non-self through homophilic protocadherin interactions. In mammals, the protocadherin gene family counts about 50 different genes. By hetero-multimerization, protocadherins are capable of generating an impressive number of molecular interfaces. Surprisingly, in the California two-spot octopus, Octopus bimaculoides, an invertebrate belonging to the Phylum Mollusca, over 160 protocadherins (PCDHs) have been identified. Here we briefly discuss the role of PCDHs in neural wiring and conduct a comparative study of the protocadherin gene family in two closely related octopus species, Octopus vulgaris and O. bimaculoides. A first glance at the expression patterns of protocadherins in O. vulgaris is also provided. Finally, we comment on PCDH evolution in the light of invertebrate nervous system plasticity

Proteasome Nuclear Import Mediated by Arc3 Can Influence Efficient DNA Damage Repair and Mitosis in Schizosaccharomyces Pombe

Proteasomes must efficiently remove their substrates throughout the cells in a timely manner as many of these proteins can be toxic. This study shows that proteasomes can do so efficiently because they are highly mobile. Furthermore this study uncovers that proteasome mobility requires functional Arc3, a subunit of the Arp2/3 complex

Cell Cycle Regulation and Cytoskeletal Remodelling Are Critical Processes in the Nutritional Programming of Embryonic Development

Many mechanisms purport to explain how nutritional signals during early development are manifested as disease in the adult offspring. While these describe processes leading from nutritional insult to development of the actual pathology, the initial underlying cause of the programming effect remains elusive. To establish the primary drivers of programming, this study aimed to capture embryonic gene and protein changes in the whole embryo at the time of nutritional insult rather than downstream phenotypic effects. By using a cross-over design of two well established models of maternal protein and iron restriction we aimed to identify putative common “gatekeepers” which may drive nutritional programming