First record of pughead deformity in Myrichthys ocellatus (Ophichthidae) and Ephinephelus marginatus (Epinephelidae)

Pugheadness has being recorded in a wide variety of fish families on both natural and non-natural environments, though encountering pughead fish in wild population is rare. Here, we present two new records of pugheadness in the wild, for Myrichthys ocellatus (Ophichthidae), and for Epinephelus marginatus (Epinephelidae). An up to date compilation of the 39 published pugheadness in fish is presented. We believe that with the advancement of information and communication technology in social networks, more records of deformities in fish species will show up through the lenses of citizen science.     

2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.     

Congenital anonychia and brachydactyly of the left foot - Cooks syndrome variant: Case report and review of literature

Cooks syndrome is characterized by familial congenital anonychia or onychodystrophy, hypoplasia or absence of distal phalanges of the hands and feet with brachydactyly of the fifth finger and digitalization of the thumb (triphalangism). It is listed as a “rare disease” by the Office of Rare Diseases of the National Institutes of Health. Here, we report a case of congenital anonychia and brachydactyly of the left foot, which possibly is a variant of Cooks syndrome with a positive family history of similar deformity.     

miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression

The spindle assembly checkpoint (SAC) is a ‘wait-anaphase'' mechanism that has evolved in eukaryotic cells in response to the stochastic nature of chromosome–spindle attachments. In the recent past, different aspects of the SAC regulation have been described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 – which functions to inhibit anaphase entry till the chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125b.     

Dysregulation of Cav1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

Mutations in the gene encoding Ca_v1.4, CACNA1F_, are associated with visual disorders including X-linked incomplete congenital stationary night blindness type 2 (CSNB2). In mice lacking Ca_v1.4 channels, there are defects in the development of “ribbon” synapses formed between photoreceptors (PRs) and second-order neurons. However, many CSNB2 mutations disrupt the function rather than expression of Ca_v1.4 channels. Whether defects in PR synapse development due to altered Ca_v1.4 function are common features contributing to the pathogenesis of CSNB2 is unknown. To resolve this issue, we profiled changes in the subcellular distribution of Ca_v1.4 channels and synapse morphology during development in wild-type (WT) mice and mouse models of CSNB2. Using Ca_v1.4-selective antibodies, we found that Ca_v1.4 channels associate with ribbon precursors early in development and are concentrated at both rod and cone PR synapses in the mature retina. In mouse models of CSNB2 in which the voltage-dependence of Ca_v1.4 activation is either enhanced (Ca_v1.4_I756T) or inhibited (CaBP4 KO), the initial stages of PR synaptic ribbon formation are largely unaffected. However, after postnatal day 13, many PR ribbons retain the immature morphology. This synaptic abnormality corresponds in severity to the defect in synaptic transmission in the adult mutant mice, suggesting that lack of sufficient mature synapses contributes to vision impairment in Ca_v1.4_I756T and CaBP4 KO mice. Our results demonstrate the importance of proper Ca_v1.4 function for efficient PR synapse maturation, and that dysregulation of Ca_v1.4 channels in CSNB2 may have synaptopathic consequences.