The evolution of centriole degradation in mouse sperm.

Centrioles are subcellular organelles found at the cilia base with an evolutionarily conserved structure and a shock absorber-like function. In sperm, centrioles are found at the flagellum base and are essential for embryo development in basal animals. Yet, sperm centrioles have evolved diverse forms, sometimes acting like a transmission system, as in cattle, and sometimes becoming dispensable, as in house mice. How the essential sperm centriole evolved to become dispensable in some organisms is unclear. Here, we test the hypothesis that this transition occurred through a cascade of evolutionary changes to the proteins, structure, and function of sperm centrioles and was possibly driven by sperm competition. We found that the final steps in this cascade are associated with a change in the primary structure of the centriolar inner scaffold protein FAM161A in rodents. This information provides the first insight into the molecular mechanisms and adaptive evolution underlying a major evolutionary transition within the internal structure of the mammalian sperm neck.

Use of midodrine and fludrocortisone in neurogenic shock: A case report.

Our case report includes a 42 year old male who had C6-C7 fracture dislocation with complete spinal cord injury following a motor vehicle accident. The patient underwent combined anterior and posterior fixation of the cervical spine. However, the patient had hypotension as a part of neurogenic shock and required vasopressor to maintain mean arterial pressure. The patient was treated in Intensive Care Unit with noradrenaline infusion to maintain mean arterial pressure but it was really challenging to stop the vasopressor. The patient was started on oral Midodrine and Fludrocortisone; vasopressor dose was tapered and finally stopped.

A dynamic basal complex modulates mammalian sperm movement.

Reproductive success depends on efficient sperm movement driven by axonemal dynein-mediated microtubule sliding. Models predict sliding at the base of the tail - the centriole - but such sliding has never been observed. Centrioles are ancient organelles with a conserved architecture; their rigidity is thought to restrict microtubule sliding. Here, we show that, in mammalian sperm, the atypical distal centriole (DC) and its surrounding atypical pericentriolar matrix form a dynamic basal complex (DBC) that facilitates a cascade of internal sliding deformations, coupling tail beating with asymmetric head kinking. During asymmetric tail beating, the DC's right side and its surroundings slide ~300 nm rostrally relative to the left side. The deformation throughout the DBC is transmitted to the head-tail junction; thus, the head tilts to the left, generating a kinking motion. These findings suggest that the DBC evolved as a dynamic linker coupling sperm head and tail into a single self-coordinated system.

Posterior reversible encephalopathy syndrome presenting as refractory status epilepticus in a patient taking Mycophenolate mofetil for IgA nephropathy: A case report.

•Posterior reversible encephalopathy syndrome is one of the numerous causes of status epilepticus and it should be kept in mind while encountering such clinical scenario.•Mycophenolate mofetil can be contributory cause of PRES.•Prompt recognition and timely intervention is a key to full recovery without any residual neurological deficits after refractory status epilepticus.

Operationalisation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 trials in a low and lower-middle income critical care learning health system.

The Randomized Embedded Multifactorial Adaptive Platform (REMAP-CAP) adapted for COVID-19) trial is a global adaptive platform trial of hospitalised patients with COVID-19. We describe implementation in three countries under the umbrella of the Wellcome supported Low and Middle Income Country (LMIC) critical  care network: Collaboration for Research, Implementation and Training in Asia (CCA). The collaboration sought to overcome known barriers to multi centre-clinical trials in resource-limited settings. Methods described focused on six aspects of implementation: i, Strengthening an existing community of practice; ii, Remote study site recruitment, training and support; iii, Harmonising the REMAP CAP- COVID trial with existing care processes; iv, Embedding REMAP CAP- COVID case report form into the existing CCA registry platform, v, Context specific adaptation and data management; vi, Alignment with existing pandemic and critical care research in the CCA. Methods described here may enable other LMIC sites to participate as equal partners in international critical care trials of urgent public health importance, both during this pandemic and beyond.

COVID-19: Current Understanding of Pathophysiology.

Coronavirus disease 2019 has emerged as a global pandemic, affecting millions of people across the globe. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the human cell after binding to the Angiotensin-Converting Enzyme 2 receptors, that are present in various organs. The involvement of the respiratory system is common and may progress to acute respiratory distress syndrome. Besides the involvement of respiratory system other systems like cardiovascular, renal, gastrointestinal and central nervous are not uncommon. In-depth understanding of the pathophysiological basis of organs and systems involvement and disease progression aids in the safe and effective management of the COVID-19 patients. It also helps to guide future well-designed clinical trials, which is the need of time. This review aims to explore the current understanding of pathophysiological basis of various organ system involvement in patients with COVID-19, that can have relevance for patient management and future research. We reviewed the articles in various databases to assemble the current evidences. Keywords: Coronavirus disease 2019; COVID-19; pathophysiology; severe acute respiratory syndrome coronavirus 2.

Tubercular meningitis presenting as cerebral salt wasting syndrome in an adult: A case report.

INTRODUCTION: Cerebral salt wasting syndrome (CSWS) is a cause of hyponatremia in the setting of intracranial pathologies such as Central Nervous System (CNS) trauma, infections, and tumors. It is important to differentiate CSWS from the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as their management differs. CSWS leads to hypovolemia as opposed to euvolemia or hypervolemia in SIADH. SIADH is managed with fluid restriction and this could worsen CSWS which is managed with adminstration of intravenous crystalloids to correct hyponatremia. CASE SUMMARY: A 42-year-old male was admitted after a week of low-grade fever with easy fatigability, hypersomnolence, and excessive thirst. He had polyuria which started 5 days before presentation, and unintentionally lost 3 kg of weight in the past month. He had orthostatic hypotension, and was dehydrated, but vital signs were normal with the exception of his temperature. Cerebrospinal fluid (CSF) analysis revealed a glucose of 42 mg/dl, protein 170 mg/dl, cell count 28/mm3 with 65% lymphocytes which was consistant with tubercular meningitis. CSF AFB culture was positive in addition to a positive CSF PCR for M. tuberculosis. DISCUSSION: Presentation of CNS infection with tuberculosis may be non-specific and its insidious onset could lead to delayed or missed diagnosis; however persistent constitutional symptoms and signs with history of weight loss and a close contact with tuberculosis may raise the possibility of tuberculosis. Early diagnosis and treatment has an excellent prognosis, but any delay contributes to death and disability despite anti-tubercular drug therapy.CSWS should be managed with salt and volume replacement, but more importantly, the causative CNS insult should also be confirmed and addressed.

Staphylococcal toxic shock syndrome in a lactating mother with breast abscess: A case report.

INTRODUCTION: The highest risk for Staphylococcal Toxic Shock Syndrome are female patients with pre-existing Staphylococcal vaginal colonization who frequently use contraceptive sponges, diaphragms or tampons. In addition patients with burns, soft tissue injures, retained nasal packing, post-abortion, post-surgical, post intrauterine device placement and abscess formation are also at high risk. CASE PRESENTATION: A 19 years old female complaint of high fever with altered level of consciousness. She also had history of nausea, vomiting, diarrhea and pain on her left breast for 5 days. She developed desquamation on her palms and soles on the day three of her admission to ICU. Ultrasonography of her left breast showed 2*2*1 cm abscess collection and the culture report from breast abscess showed Staphylococcus aureus, sensitive to clindamycin, vancomycin and resistant to methicillin. She showed clinical improvement after commencing vancomycin and clindamycin as per culture sensitivity report of breast abscess. DISCUSSION: Toxic shock syndrome secondary to breast abscess in adult is infrequently reported. The diagnosis of Toxic shock syndrome is made by the Centers for Disease Control and Prevention (CDC) definition. Antibiotics for treatment of this condition should include a penicillinase-resistant penicillin, cephalosporin, or vancomycin (in methicillin-resistant S. aureus prevalent areas) in combination with either clindamycin or linezolid. CONCLUSION: Treatment for breast abscess warrants incision and drainage as important as antibiotics with anti-toxin. Focused history, physical examination, and laboratory investigations are crucial for the diagnosis and management of this condition.

Acute mountain sickness induced diabetic ketoacidosis managed with hemodialysis: A case report.

INTRODUCTION: The risk of developing ketoacidosis in patients with type 1 diabetes at high altitude is high. Anorexia associated with acute mountain sickness, dehydration and additional exercise associated with climbing exacerbates the generation of ketones and the development of ketoacidosis. CASE PRESENTATION: A 33-year-old gentleman with known history of uncontrolled type 1 diabetes mellitus trekked to Everest Base Camp at an altitude of 3440 m and became unwell. He developed altered sensorium and shortness of breath. He ingested eight tablets of acetazolamide (250 mg each) to address these symptoms. Upon presentation to emergency, he was diagnosed with severe diabetes ketoacidosis (DKA) with shock. Resuscitation was started with fluid, insulin, vasopressors and mechanical ventilation. Despite adequate fluid resuscitation, insulin, bicarbonates and other supportive measures, his acidosis and shock persisted and then managed with hemodialysis. After the first session of hemodialysis, improvement in acidosis and shock was noted. He was successfully extubated and later discharged. DISCUSSION: In this case report, DKA due to acute mountain sickness was complicated by acetazolamide use and noncompliance to his regular insulin intake. There is no proper guideline regarding the role of renal replacement therapy in management of DKA. However, evidence of hemodialysis in DKA is limited to few case reports. Improvement seen in our patient after dialysis is related to dialyzable nature of acetazolamide. CONCLUSION: We present a case of a severe DKA potentially precipitated by acute mountain sickness, use of acetazolamide, noncompliance to his regular insulin intake and managed with hemodialysis in addition to conventional treatment for DKA.

Poc1B and Sas-6 Function Together during the Atypical Centriole Formation in Drosophila melanogaster.

Insects and mammals have atypical centrioles in their sperm. However, it is unclear how these atypical centrioles form. Drosophila melanogaster sperm has one typical centriole called the giant centriole (GC) and one atypical centriole called the proximal centriole-like structure (PCL). During early sperm development, centriole duplication factors such as Ana2 and Sas-6 are recruited to the GC base to initiate PCL formation. The centriolar protein, Poc1B, is also recruited at this initiation stage, but its precise role during PCL formation is unclear. Here, we show that Poc1B recruitment was dependent on Sas-6, that Poc1B had effects on cellular and PCL Sas-6, and that Poc1B and Sas-6 were colocalized in the PCL/centriole core. These findings suggest that Sas-6 and Poc1B interact during PCL formation. Co-overexpression of Ana2 and Sas-6 induced the formation of ectopic particles that contained endogenous Poc1 proteins and were composed of PCL-like structures. These structures were disrupted in Poc1 mutant flies, suggesting that Poc1 proteins stabilize the PCL-like structures. Lastly, Poc1B and Sas-6 co-overexpression also induced the formation of PCL-like structures, suggesting that they can function together during the formation of the PCL. Overall, our findings suggest that Poc1B and Sas-6 function together during PCL formation.

Posterior reversible encephalopathy syndrome in association with exacerbation of chronic obstructive pulmonary disease: a case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a reversible clinical and neurological entity. There are varieties of comorbid conditions which are associated with PRES. Chronic obstructive pulmonary disease (COPD) is a rare predisposing factor for the development of PRES. CASE PRESENTATION: A 55 year old female who was being treated for acute exacerbation of COPD developed altered sensorium and multiple episodes of seizure. Characteristic imaging findings and associated clinical symptoms led us to a diagnosis of PRES in our patient. CONCLUSION: Association of PRES and COPD is a rare entity. The diagnosis of PRES should be brought to mind if there is encephalopathy or seizure in COPD exacerbation.

Author Correction: A novel atypical sperm centriole is functional during human fertilization.

In the original version of this Article, the affiliation details for Jadranka Loncarek and Vito Mennella were incorrectly given as 'Cell Biology Program, The Hospital for Sick Children, Department of Biochemistry, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada' and 'Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, 1050 Boyles Street, Frederick, MD, 21702, USA', respectively. This has now been corrected in both the PDF and HTML versions of the Article.

A novel atypical sperm centriole is functional during human fertilization.

The inheritance of the centrosome during human fertilization remains mysterious. Here we show that the sperm centrosome contains, in addition to the known typical barrel-shaped centriole (the proximal centriole, PC), a surrounding matrix (pericentriolar material, PCM), and an atypical centriole (distal centriole, DC) composed of splayed microtubules surrounding previously undescribed rods of centriole luminal proteins. The sperm centrosome is remodeled by both reduction and enrichment of specific proteins and the formation of these rods during spermatogenesis. In vivo and in vitro investigations show that the flagellum-attached, atypical DC is capable of recruiting PCM, forming a daughter centriole, and localizing to the spindle pole during mitosis. Altogether, we show that the DC is compositionally and structurally remodeled into an atypical centriole, which functions as the zygote's second centriole. These findings now provide novel avenues for diagnostics and therapeutic strategies for male infertility, and insights into early embryo developmental defects.