Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases ...of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10
) and PKP4 (P=8.67 × 10
); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P
=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r
=0.28 P=2.99 × 10
), SCZ (r
=0.34 P=4.37 × 10
) and MDD (r
=0.57 P=1.04 × 10
). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
Thyroid dysfunction is recognized in the newborns of mothers affected by Graves' disease during pregnancy. We describe the development of concurrent hyperthyroidism and hypothyroidism in the twin ...infants of a mother with Graves' disease diagnosed during pregnancy.
In the ovine endometrium, dramatic increases in gastrin-releasing peptide (GRP) mRNA and immunoreactivity are observed during the luteal regression phase of the oestrous cycle (24-fold) and during ...pregnancy (at least 150-fold). This study sought to determine whether oestrogen and/or progesterone were responsible for the temporal regulation of GRP observed in the uterus. Ovariectomized sheep were divided into four groups (n=4), as follows: 1, untreated; 2, given subcutaneous and intravaginal progesterone implants; 3, given subcutaneous oestrogen implants; and 4, treated with both oestrogen and progesterone. After 10 days, the animals were sacrificed and plasma, pituitary and endometrium were obtained. A fifth group of sheep with intact ovaries was included. Analysis of endometrial GRP-immunoreactivity (GRP-ir) revealed a twofold drop for groups treated with oestrogen, progesterone or both hormones. A dramatic reduction in endometrial GRP mRNA was o! bserved in the group treated with both hormones. GRP-ir was measured in whole pituitaries and found to vary greatly (1.7-53.7 pmol/g tissue) within all groups of ovariectomized animals. There were no significant differences between any of the five groups. A significant reduction in circulating GRP-ir was observed after 10 days of treatment with either oestrogen or progesterone. These studies demonstrate that, in sheep, the synthesis, storage and secretion of GRP are differentially affected by oestrogen and progesterone. Regulation appears to be tissue specific since GRP content in the pituitary is unchanged by oestrogen or progesterone whereas GRP expression in the endometrium is inhibited. Changes in GRP mRNA expression did not correlate with changes in endometrial expression of mRNA for oestrogen receptor alpha, oestrogen receptor beta and the progesterone receptor. This study is the first reported demonstration that expression of the GRP gene can be influenced by the presence of ovarian steroids, with the conclusion that oestrogen and/or progesterone act as negative regulators of endometrial GRP expression.
This collection of essays examines the relatively new, and frequently overlooked, political phenomenon in post-colonial Africa of chieftaincy “re-inventing” itself. The traditional authority of ...chiefs has been one of Africa’s missing voices who are now bringing new resources to the challenges that AIDS, gender, governance, and development pose to the peoples of Africa. Reinventing African Chieftaincy in the Age of AIDS, Gender, Governance, and Development presents new research in Ghana, Botswana, and South Africa, providing the broadest geographic African coverage on the topic of African chieftaincy. The nineteen authors, many of them emerging scholars from Africa, are all members of the Traditional Authority Applied Research Network (TAARN). Their essays give critical insight into the transformation processes of chieftaincy from the end of the colonial/apartheid periods to the present. They also examine the realities of male and female traditional leaders in reinventing their legitimacy and their political offices in the age of great social and political unrest, health issues and governance and development challenges. With Contributions By: Donald I. Ray, Tim Quinlan, Keshav C. Sharma, Tacita A.O. Clarke, Brian Keating, Kereng Daniel Lebogang Kgotleng, Mpilo Parl Sithole, Mpho G. Molmo, Robert Thornton, Mogopodi Lekorwe, Morgan Nyendu, Sibongiseni Mkhize, Shahid Vawda, Christiane Owusu-Sarpong, Kimberly Schoon, Sherri Brown, Wilhelmina J. Donkoh, and Gaelle Eizlini.
Patients presenting with neurological deficit secondary to metastatic epidural spinal cord compression (MESCC) are often treated with surgery in combination with high-dose corticosteroids. Despite ...steroids being commonly used, the evidence regarding the effect of corticosteroids on patient outcomes is limited. The objective of this study was to describe the effect of corticosteroid use on preoperative neurological function in patients with MESCC.
Patients who underwent surgery between August 2013 and February 2017 for the treatment of spinal metastases and received steroids to prevent neurologic deficits were included. Data regarding demographics, diagnosis, treatment, neurological function, adverse events, health-related quality of life, and survival were extracted from an international multicenter prospective cohort.
A total of 30 patients treated surgically and receiving steroids at baseline were identified. Patients had a mean age of 58.2 years (standard deviation, 11.2 years) at time of surgery. Preoperatively, 50% of the patients experienced deterioration of neurological function, while in 30% neurological function was stable and 20% improved in neurological function. Lengthier steroid use did not correlate with improved or stabilized neurological function. Postoperative adverse events were observed in 18 patients (60%). Patients that stabilized or improved neurologically after steroid use showed a trend towards improved survival at 3- and 24-month postsurgery.
This study described the effect of steroids on preoperative neurological function in patients with MESCC. Stabilization or improvement of preoperative neurological function occurred in 50% of the patients.
Background : Urgent laparoscopic cholecystectomy has become the gold standard for the treatment of acute gallstone disease. Since 2005 we have implemented a consultant-delivered urgent surgical ...service for this condition. In an attempt to increase the capacity of this service, we have recently introduced a new policy of also allowing selected trainee surgeons to perform urgent laparoscopic cholecystectomy with consultant assistance available on request. The purpose of this study was to audit our initial experience of this new service.
Methods : Patients with acute gallstone disease had their surgery performed by a consultant or a trainee operating independently with consultant assistance available only on request. Allocation was based purely on surgeon availability. The clinical outcomes of 50 consecutive trainee and 50 consecutive consultant cases were compared and an attempt made to identify pre-operative predictors of technically-demanding trainee cases requiring consultant intervention. Results : The mean operating time of trainees was significantly longer than consultants (80 ± 5 mins vs 55 ± 4 mins, p < 0.001) although the conversion rates for trainees (4%) and consultants (2%) were similar. There were no significant differences between the groups with respect to postoperative morbidity. Of the 50 trainee cases, consultant intervention was required in 12 (24%) cases. There were no statistically significant pre-operative predictors of requirement for consultant assistance.
Conclusions : Urgent laparoscopic cholecystectomy may be performed independently by appropriately skilled trainees within a consultant-led service. Although consultant intervention is often not required, the requirement for consultant assistance cannot be easily predicted based on pre-operative data.
Oxidized phospholipids carried on the apolipoprotein B-100 (OxPL-apoB) component of Lp(a) are predictive of coronary heart disease (CHD), but the role of oxidized phospholipids carried on plasminogen ...(OxPL-PLG) is unknown. We examined the independent effects of OxPL-apoB and OxPL-PLG for risk of CHD before and after adjustment for Lp(a).
Plasma levels of OxPL-apoB, OxPL-PLG, plasminogen and Lp(a) were measured in the PROCARDIS study of early-onset CHD (906 cases/858 controls). Multivariable logistic regression was used to estimate the odds ratios (OR) for each biomarker with CHD after adjustment for established risk factors.
Mean levels of OxPL-apoB were higher in cases than controls, but levels of OxPL-PLG and plasminogen were similar. For OxPL-apoB, individuals in the top vs bottom fifth had 2-fold higher age and sex-adjusted OR of CHD (OR = 2.61 95%CI: 1.91, 3.55), which were partially attenuated after adjustment for established risk factors. The findings for OxPL-apoB and CHD in PROCARDIS were comparable with those of a meta-analysis of all such studies. However, the associations of OxPL-apoB with CHD were fully attenuated by additional adjustment for Lp(a) (OR = 0.93 0.54,1.60). Neither OxPL-PLG nor plasminogen were associated with CHD. Overall, there were no differences in the predictive value for CHD of high vs normal levels (<20th or >80th percentile) of OxPL-apoB, OxPL-PLG, plasminogen or Lp(a) after stratifying for each other.
These results highlight the context-dependency of OxPL in plasma and suggest that their associated risk of CHD is chiefly mediated by their carriage on Lp(a).
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•Plasma levels of oxidized phospholipids carried on apolipoprotein B-100 are predictive of coronary heart disease.•Plasma levels of oxidized phospholipids carried on plasminogen and plasminogen were unrelated to risk of coronary heart disease.•The effects of oxidized phospholipids on risk of coronary heart disease are chiefly mediated by their carriage on Lp(a).
We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients.
The Systemic Lupus International ...Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality.
We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point).
Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.
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