Obvious Anatomical Abnormalities Research Articles

Histological and clinical evaluation of discarded kidneys in a European cohort of deceased brain death donor kidneys of marginal quality.

Despite organ shortages, the discard rate of deceased donor kidneys is high. Risk factors for this trend warrant further study. We investigated reasons for discard in a cohort of brain death donors with marginal kidneys and procurement biopsies. Paraffin embedded procurement biopsies were systematically reevaluated and graded for the purpose of the study. Assessment included percentage of global glomerulosclerosis, Banff Lesion scores and tubular epithelial damage. Donor-, transplant process-, perfusion quality-, histopathology-, and recipient-related parameters were compared between discarded and transplanted organs. Although most clinical characteristics were similar between donors whose kidneys were transplanted and those whose kidneys were procured but discarded, discarded kidneys were more likely to be from donors with hepatitis C, to have undergone wedge biopsies, to show changes of acute and chronic injury and to be deemed poor quality. Except for obvious anatomic abnormalities, kidneys were often discarded due to the findings of procurement biopsies. Donors of kidneys discarded for histologic reasons more often had hypertension, coronary artery disease, stroke, and increased serum creatinine. The reason for discard was unknown in 20% of cases. Discarded kidneys came from donors who appeared to be clinically similar to donors whose kidneys were utilized for transplant. A considerable proportion of discarded kidneys were of acceptable quality. The analysis of theoutcome of every recovered organ could help to overcome this problem. Procurement biopsies more often lead to discard than to transplantation of recovered organs. Proper handling during allocation has to be determined.

The RNA-binding protein QKI governs a muscle-specific alternative splicing program that shapes the contractile function of cardiomyocytes.

In the heart, splicing factors orchestrate the functional properties of cardiomyocytes by regulating the alternative splicing of multiple genes. Work in embryonic stem cells has shown that the splicing factor Quaking (QKI) regulates alternative splicing during cardiomyocyte differentiation. However, the relevance and function of QKI in adult cardiomyocytes remains unknown. In this study, we aim to identify the in vivo function of QKI in the adult mouse heart. We generated mice with conditional deletion of QKI in cardiomyocytes by the Cre-Lox system. Mice with cardiomyocyte-specific deletion of QKI died during the foetal period (E14.5), without obvious anatomical abnormalities of the heart. Adult mice with tamoxifen-inducible QKI deletion rapidly developed heart failure associated with severe disruption of sarcomeres, already 7 days after knocking out QKI. RNA sequencing revealed that QKI regulates the alternative splicing of more than 1000 genes, including sarcomere and cytoskeletal components, calcium-handling genes, and (post-)transcriptional regulators. Many of these splicing changes corresponded to the loss of muscle-specific isoforms in the heart. Forced overexpression of QKI in cultured neonatal rat ventricular myocytes directed these splicing events in the opposite direction and enhanced contractility of cardiomyocytes. Altogether, our findings show that QKI is an important regulator of the muscle-specific alternative splicing program that builds the contractile apparatus of cardiomyocytes.

ROLE OF SEPTOPLASTY AND FUNCTIONAL ENDOSCOPIC SINUS SURGERY IN THE TREATMENT OF RHINOGENIC HEADACHE

INTRODUCTION: Rhinogenic headaches are basically described as headache or facial pain caused by rhinological source. The presence of nasal symptoms & it’s temporal relationship with headache is the key factor that can guide the diagnosis and patient management. AIMS: This study aims to evaluate the efficacy of Septoplasty with Functional endoscopic sinus surgery (F.E.S.S) in the management of Rhinogenic headache. MATERIALS & METHODS: It was a Prospective study conducted in M.G.M Medical College & associated M.Y group of hospitals from March 2019 to March 2020. 64 patients of age group 18 years to 60 years having chronic rhinosinusitis with headache included in the study. After detailed history and thorough examination, nasal endoscopy and CT Paranasal sinus was done. Patients not responding to conservative management were selected for undergoing functional endoscopic sinus surgery. RESULTS: A total of 64 patients were included in the study,34 male & 30 female with the mean age group of 31.4 & 30.1 years respectively. Out of 64 patients,67% were completely free from headache,15% were significantly improved,7% had mild relief & 11% did not show any benefit in headache from surgery. Postoperatively, there was statistically significant difference was found patient’s symptomatology (i.e. p value =0.0165). CONCLUSION: To make the diagnosis both anatomical & infective factors needed to be considered. Correction of obvious anatomic abnormalities in carefully selected patients can significantly improve several important clinical outcomes from abolishing headache completely to decreasing its intensity and frequency of episodes. KEY-WORDS: Rhinogenic headaches, Septoplasty, Chronic rhinosinusitis, F.E.S.S, Nasal endoscopy

C11ORF74 interacts with the IFT-A complex and participates in ciliary BBSome localization.

Cilia are organelles that serve as cellular antennae. Intraflagellar transport particles containing the IFT-A and IFT-B complexes mediate bidirectional trafficking of ciliary proteins. Particularly, in concert with the BBSome complex, IFT particles play an essential role in trafficking of ciliary G-protein-coupled receptors (GPCRs). Therefore, proteins interacting with the IFT components are potential regulators of ciliary protein trafficking. We here revealed that an uncharacterized protein, C11ORF74, interacts with the IFT-A complex via the IFT122 subunit and is accumulated at the distal tip in the absence of an IFT-A subunit IFT139, suggesting that at least a fraction of C11ORF74 molecules can be transported towards the ciliary tip by associating with the IFT-A complex, although its majority might be out of cilia at steady state. In C11ORF74-knockout (KO) cells, the BBSome components cannot enter cilia. However, trafficking of Smoothened or GPR161, both of which are ciliary GPCRs involved in Hedgehog signalling and undergo BBSome-dependent trafficking, was not affected in the absence of C11ORF74. In addition, C11orf74/B230118H07Rik- KO mice demonstrated no obvious anatomical abnormalities associated with ciliary dysfunctions. Given that C11ORF74 is conserved across vertebrates, but not found in other ciliated organisms, such as nematodes and Chlamydomonas, it might play limited roles involving cilia.

Measurement of subclavicular pressure on the subclavian artery and brachial plexus in the costoclavicular space during provocative positioning for thoracic outlet syndrome

BackgroundThoracic outlet syndrome is thought to be caused by compression of the brachial plexus or subclavian artery in the interscalene, costoclavicular, or subcoracoid space. Some provocative tests are widely used for diagnosing thoracic outlet syndrome. However, whether provocative positions actually compress the neurovascular bundle in these spaces remains unclear. The purpose of this study was to investigate the possibility of neurovascular bundle compression in the costoclavicular space by measuring the pressure applied to the brachial plexus and subclavian artery in provocative positions. MethodsBilateral shoulders of eight fresh-frozen transthoracic human cadavers with no obvious anatomical abnormalities were used in this study. There were three female and five male cadavers with a mean age of 81.7 years (range 72–90 years). The pressure on the brachial plexus and subclavian artery between the clavicle and first rib were measured using a 0.13-mm thin pressure sensor in each of four provocative positions (depressed position, alternative Eden position, throwing position, Wright position). ResultsNerve contact pressure was increased in seven shoulders in the Wright position (2.87 ± 3.13 N/cm2; range 0.81–9.76 N/cm2). The frequency of nerve compression in the Wright position was significantly higher when compared to that in the other three limb positions (P = 0.018). Artery contact pressure was increased in three shoulders in the Wright position (mean 0.59 ± 0.13 N/cm2; range 0.45–0.7 N/cm2). As was the case with nerve compression, the frequency of compression tended to be higher for the Wright position, but no significant difference was seen. ConclusionsIn four of eight specimens with no obvious anatomical abnormalities, the brachial plexus was compressed in the costoclavicular space in the Wright position. The Wright position thus may be a useful position for inducing nerve compression in the costoclavicular space.

Dissociated fear and spatial learning in mice with deficiency of ataxin-2.

Mouse models with physiological and behavioral differences attributable to differential plasticity of hippocampal and amygdalar neuronal networks are rare. We previously generated ataxin-2 (Atxn2) knockout mice and demonstrated that these animals lacked obvious anatomical abnormalities of the CNS, but showed marked obesity and reduced fertility. We now report on behavioral changes as a consequence of Atxn2-deficiency. Atxn2-deficiency was associated with impaired long-term potentiation (LTP) in the amygdala, but normal LTP in the hippocampus. Intact hippocampal plasticity was associated behaviorally with normal Morris Water maze testing. Impaired amygdala plasticity was associated with reduced cued and contextual fear conditioning. Conditioned taste aversion, however, was normal. In addition, knockout mice showed decreased innate fear in several tests and motor hyperactivity in open cage testing. Our results suggest that Atxn2-deficiency results in a specific set of behavioral and cellular disturbances that include motor hyperactivity and abnormal fear-related behaviors, but intact hippocampal function. This animal model may be useful for the study of anxiety disorders and should encourage studies of anxiety in patients with spinocerebellar ataxia type 2 (SCA2).

Bilateral volume reduction of the superior temporal areas in Landau-Kleffner syndrome.

No specific anatomic abnormalities have been detected in typical Landau-Kleffner syndrome (LKS), an acquired epileptic aphasia with language regression in children. In four children with typical LKS without obvious anatomic abnormalities, the authors performed MRI volumetric analysis of various neocortical regions and subcortical substructures. Volume reduction was detected in bilateral superior temporal areas (26 to 51%), specifically in planum temporale (25 to 63%) and superior temporal gyrus (25 to 57%), where receptive language is localized.

Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein specifically expressed in astrocytes in the CNS. To examine the function of GFAP in vivo, the Gfap gene was disrupted by gene targeting in embryonic stem cells. Mice homozygous for the mutation were completely devoid of GFAP but exhibited normal development and showed no obvious anatomical abnormalities in the CNS. When inoculated with infectious scrapie prions, the mutant mice exhibited neuropathological changes typical of prion diseases. Infectious prions accumulated in brains of the mutant mice to a degree similar to that in control littermates. These results suggest that GFAP is not essential for the morphogenesis of the CNS or for astrocytic responses against neuronal injury. The results argue against the hypothesis that GFAP plays a crucial role in the pathogenesis of prion diseases.

Studies of the bladder defense mechanism. II. Postoperative cystitis in the elderly.

AbstractChronic postoperative cystitis in the elderly patient is a difficult problem, and is especially annoying if all obvious anatomic abnormalities have been corrected. This study of 20 such patients who underwent bladder surgery indicates that several local resistance factors may be related to this continued urinary infection. In elderly postoperative patients with chronic cystitis the bladder defense mechanisms have reached such a state of imbalance that they cannot cope with the invading organisms either by the mechanism of voiding or by vesical‐wall defense factors. The relative importance of the various cellular and serologic local defense mechanisms in resisting bacteria in bladder urine and the bladder mucus layer, mucosa or submucosa is not known.There is no apparent quantitative histologic defect in the local bladder cellular response of the elderly patient. Therefore, a decreased quality of response is implied. In addition, trauma created by indwelling catheterization or by surgery destroys the anatomic integrity of the bladder wall and may thereby encourage the development of deep‐seated infection by permitting tissue invasion. Foci of tissue infestation by E. coli were demonstrated in 1 of 2 patients in whom it was possible to make such a study. These foci are not subject to the normal voiding defense mechanism and the antibacterial factors within the bladder or urine; they can be eliminated only by inflammatory cells, antibodies, or antibacterial agents capable of attaining bactericidal tissue levels.Two axioms were confirmed by this study: 1) any period of preoperative indwelling catheterization should be as brief as possible, and 2) specific antimicrobial therapy should be planned preoperatively so that surgery takes place at a time when the urine and tissues are sterile; this sterility should be maintained until all foreign bodies, such as catheters, are removed from the urinary tract.