Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP- sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.      

Patch test responses to Malassezia pachydermatis in healthy dogs.

The effects of the patch test application of Malassezia pachydermatis extracts to normal canine skin were evaluated in eight healthy beagle dogs. Antigens (4 and 0.4 mg/ml) and saline controls were applied for 48 h using filter paper discs in Finn chambers. At the first test, two dogs showed patch test reactivity 20 min and 24 h after patch removal. Four out of six dogs that did not react to the first patch test showed reactivity when re-tested on day 8. Two remaining dogs were patch tested for a third time on day 15, after 7 days of cutaneous challenge with suspensions of M. pachydermatis cells, but failed to display reactivity. Positive patch test reactions were characterized histologically by mild epidermal hyperplasia, superficial dermal oedema and mild to moderate perivascular, periadnexal and interstitial infiltrates of neutrophils and CD3+ lymphocytes. Four dogs showed delayed intradermal test reactivity to M. pachydermatis antigens but intradermal and patch test reactivity did not correlate. This study indicates that patch test reactivity to M. pachydermatis antigen occurs in some healthy dogs exposed to the yeast, or may develop after a short period of antigen exposure. Further studies of patch test reactivity are warranted in dogs with disease associated with this cutaneous yeast.     

Alexithymia in young adulthood: a risk factor for pathological gambling

BACKGROUND: Pathological gambling is more prevalent among postsecondary students than among the general adult population. While the prevalence of pathological gambling in this group has risen over the past decade, factors underlying the development of problem gambling among university students remain largely unexplored. One early study found alexithymia to be associated with pathological gambling. The aim of the present study was to further examine the relationship between alexithymia and gambling among postsecondary students. METHODS: The relationship between alexithymia and pathological gambling was examined in 562 postsecondary students who completed the South Oaks Gambling Screen (SOGS) and the 20-item Toronto Alexithymia Scale (TAS-20). RESULTS: Approximately 12% of the sample was classified as alexithymic according to the TAS-20. These individuals were found to have significantly more gambling problems, as measured by the SOGS, than nonalexithymic individuals. Approximately 9% of the sample was classified as pathological gamblers according to the SOGS. These individuals were found to have significantly higher levels of alexithymia, as measured by the TAS-20, than nonproblem gamblers. CONCLUSIONS: Alexithymia is associated with pathological gambling and may be a risk factor among postsecondary students for developing severe gambling problems.     

Psychogenic pain: a study of marital adjustment

The marital adjustment of patients with psychogenic pain disorder was evaluated and compared with a matched group of patients with other neurotic disorders. Pain patients spouses were found to have better marital adjustment and less psychiatric morbidity than the spouses of neurotic patients. These findings are discussed in terms of the concepts of "sick role homeostasis" and "tertiary gain".     

Mental Health and Service Impacts During COVID-19 for Individuals with Serious Mental Illnesses Recently Released from Prison and Jail

The Journal of Behavioral Health Services & Research - Individuals recently released from jail or prison with serious mental illnesses may be vulnerable to the coronavirus pandemic. This study...     

The anatomy of the anterior inferior tibiofibular ligament and its relationship with the Wagstaffe fracture

BackgroundOur aim in this study was to identify the fibular footprint of the Anterior Inferior Tibiofibular Ligament (AITFL) and its relation to Wagstaffe fracture fragment size.MethodsWe examined 25 cadaveric lower limbs which were carefully dissected to identify the lateral ankle ligaments. The AITFL anatomy was compared to 40 Wagstaffe fractures identified from our ankle fracture database.ResultsThe AITFL origin was from the anterior fibular tubercle with an average length of 21.61 mm (95% CI 20.22, 22.99). The average distance of the distal aspect of the AITFL footprint to the distal fibula margin was 11.60 mm (95% CI 10.49, 12.71). In the ankle fractures analyzed, the average length of the Wagstaffe fragment was 17.88 mm (95% CI 16.21, 19.54). The average distance from the distal tip of the fibula to the Wagstaffe fracture fragment was 21.40 mm (95% CI 19.78, 23.01).In total there were 22 syndesmosis injuries. There was no statistical difference in Wagstaffe fragment size between stable and unstable groups.ConclusionThe AITFL fibular origin was both larger and more distal than the Wagstaffe fracture fragments seen in our institution. Therefore, this suggests that a ligamentous failure will also have to occur to result in syndesmotic instability. The size of fracture fragment also did not confer to syndesmotic instability on testing.Level of Evidence - 3     

Translating clinical and patient-reported data to tailored shared decision reports with predictive analytics for knee and hip arthritis

Quality of Life Research - New informatics tools can transform evidence-based information to individualized predictive reports to serve shared decisions in clinic. We developed a web-based system...     

Pre-anesthetic assessment clinics in Ontario

PURPOSE: To survey the provision of pre-anesthetic assessment clinics in hospitals in Ontario during the summer of 1997. METHODS: Mail survey questionnaire of all 300 hospitals in Ontario. RESULTS: Replies were received from 260 hospitals (86.7%) of which 131 provide anesthesia. Of these, 86% are community and 14% teaching hospitals. Regular clinics are held in 63% of these hospitals, most commonly daily. As to location, 73% are held in the outpatient department. Written guidelines detailing which patients should be referred are issued by 77% of departments. The attending surgeon is the most common source of referral (64%). Referred patients are most commonly seen by a nurse (52%) who decides on onward referral to an anesthesiologist. Services generating the most referrals are general surgery (83%), orthopedics (64%) and obstetrics/gynecology (49%). In 47% of hospitals 10-50 patients are seen per month and they travel most commonly up to 100 km. The average "no show" rate is 6.2%. Only 36% of departments assess patients the same day as seen by the surgeon. On attending the clinic, 51% can see an internist the same day in contrast to 30% being able to see a cardiologist. Pre-admission testing is available to 97% on the same day. Direct funding is available for the nurse (87%), physician (1%) and secretarial help (43%). Remuneration of the anesthesiologist is fee for service (99%) and sessional (1%). CONCLUSION: Pre-anesthetic assessment clinics are common in Ontario. More development is required to enable patients to receive all aspects of their preoperative assessment during one visit.