Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

Candida albicans is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to C. albicans pathogenicity. C. albicans strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD) that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to be virulent, whereas the zinc-binding domain was essential, as Caarv1/Caarv1 cells expressing the full-length zinc-binding domain mutants, Caarv1C3S and Caarv1C28S, were avirulent. Phenotypically, we found a direct correlation between the avirulence of Caarv1/Caarv1, Caarrv1AHD, Caarv1C3S, and Caarv1C28S cells and defects in bud site selection, septa formation and localization, and hyphal formation and elongation. Importantly, all avirulent mutant strains lacked the ability to maintain proper sterol distribution. Overall, our results have established the importance of the AHD and zinc-binding domain in fungal invasion, and have correlated an avirulent phenotype with the inability to maintain proper sterol distribution

Guideline for diagnosis and treatment of subacromial pain syndrome

Treatment of "subacromial impingement syndrome" of the shoulder has changed drastically in the past decade. The anatomical explanation as "impingement" of the rotator cuff is not sufficient to cover the pathology. "Subacromial pain syndrome", SAPS, describes the condition better. A working group formed from a number of Dutch specialist societies, joined by the Dutch Orthopedic Association, has produced a guideline based on the available scientific evidence. This resulted in a new outlook for the treatment of subacromial pain syndrome. The important conclusions and advice from this work are as follows: (1) The diagnosis SAPS can only be made using a combination of clinical tests. (2) SAPS should preferably be treated non-operatively. (3) Acute pain should be treated with analgetics if necessary. (4) Subacromial injection with corticosteroids is indicated for persistent or recurrent symptoms. (5) Diagnostic imaging is useful after 6 weeks of symptoms. Ultrasound examination is the recommended imaging, to exclude a rotator cuff rupture. (6) Occupational interventions are useful when complaints persist for longer than 6 weeks. (7) Exercise therapy should be specific and should be of low intensity and high frequency, combining eccentric training, attention to relaxation and posture, and treatment of myofascial trigger points (including stretching of the muscles) may be considered. (8) Strict immobilization and mobilization techniques are not recommended. (9) Tendinosis calcarea can be treated by shockwave (ESWT) or needling under ultrasound guidance (barbotage). (10) Rehabilitation in a specialized unit can be considered in chronic, treatment resistant SAPS, with pain perpetuating behavior. (11) There is no convincing evidence that surgical treatment for SAPS is more effective than conservature management. (12) There is no indication for the surgical treatment of asymptomatic rotator cuff tears

There are no Differences in Pretransplant Characteristics of Individuals Receiving Simultaneous Pancreas-Kidney Transplant and Individuals with Type 1 Diabetes Mellitus Receiving Living-Related Kidney Transplant

Simultaneous pancreas-kidney transplantation (SPK) recipients have longer survival compared to type 1 diabetes mellitus (DM1) cadaveric kidney recipients. However, DM1 living-related kidney transplant (KTX-LR) recipients have the same mortality as SPK recipients. It is unknown whether cardiovascular (CVD) risk factors pretransplant are similar between the two groups, SPK and DM1 KTX-LR. We analyzed pretransplant characteristics of SPK recipients (n = 39) and DM1 KTX-LR/living unrelated (LUR) recipients (KTX-LR/LUR, n = 20). In individuals who had multiple transplants, only pretransplant data from the first transplant was used. As all characteristics of KTX-LR/LUR recipients were the same, they were grouped for comparison with SPK. Pretransplant blood pressure (BP), body mass index, (BMI), hemoglobin A1c (A1c), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TG), serum creatinine, type and duration of dialysis, and duration of diabetes were compared between the two groups. Mean age at time of transplantation was 41 +/- 1 years (mean +/- SEM) for SPK versus 39 +/- 2 years for KTX-LR/LUR (P = NS). Pretransplant BP, BMI, duration of diabetes, TC, HDL, LDL, TG, and lipid agent use were not different between the groups. Pretransplant A1c was 7.8 +/- 0.3% for SPK recipients and 8.3 +/- 0.5% for KTX-LR/LUR recipients (P = NS). Pretransplant serum creatinine was higher in KTX-LR/LUR compared to SPK (7.9 +/- 0.6 mg/dL versus 5.4 +/- 0.5 mg/dL; P =.01). Except for serum creatinine, there were no significant differences in traditional CVD risk factors pretransplant. However, factors posttransplant in addition to better glucose control with SPK may still be different between SPK and KTX-LR/LUR groups

There are no Differences in Pretransplant Characteristics of Individuals Receiving Simultaneous Pancreas-Kidney Transplant and Individuals with Type 1 Diabetes Mellitus Receiving Living-Related Kidney Transplant

Simultaneous pancreas-kidney transplantation (SPK) recipients have longer survival compared to type 1 diabetes mellitus (DM1) cadaveric kidney recipients. However, DM1 living-related kidney transplant (KTX-LR) recipients have the same mortality as SPK recipients. It is unknown whether cardiovascular (CVD) risk factors pretransplant are similar between the two groups, SPK and DM1 KTX-LR. We analyzed pretransplant characteristics of SPK recipients (n = 39) and DM1 KTX-LR/living unrelated (LUR) recipients (KTX-LR/LUR, n = 20). In individuals who had multiple transplants, only pretransplant data from the first transplant was used. As all characteristics of KTX-LR/LUR recipients were the same, they were grouped for comparison with SPK. Pretransplant blood pressure (BP), body mass index, (BMI), hemoglobin A1c (A1c), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TG), serum creatinine, type and duration of dialysis, and duration of diabetes were compared between the two groups. Mean age at time of transplantation was 41 +/- 1 years (mean +/- SEM) for SPK versus 39 +/- 2 years for KTX-LR/LUR (P = NS). Pretransplant BP, BMI, duration of diabetes, TC, HDL, LDL, TG, and lipid agent use were not different between the groups. Pretransplant A1c was 7.8 +/- 0.3% for SPK recipients and 8.3 +/- 0.5% for KTX-LR/LUR recipients (P = NS). Pretransplant serum creatinine was higher in KTX-LR/LUR compared to SPK (7.9 +/- 0.6 mg/dL versus 5.4 +/- 0.5 mg/dL; P =.01). Except for serum creatinine, there were no significant differences in traditional CVD risk factors pretransplant. However, factors posttransplant in addition to better glucose control with SPK may still be different between SPK and KTX-LR/LUR groups

There are no Differences in Pretransplant Characteristics of Individuals Receiving Simultaneous Pancreas-Kidney Transplant and Individuals with Type 1 Diabetes Mellitus Receiving Living-Related Kidney Transplant

Simultaneous pancreas-kidney transplantation (SPK) recipients have longer survival compared to type 1 diabetes mellitus (DM1) cadaveric kidney recipients. However, DM1 living-related kidney transplant (KTX-LR) recipients have the same mortality as SPK recipients. It is unknown whether cardiovascular (CVD) risk factors pretransplant are similar between the two groups, SPK and DM1 KTX-LR. We analyzed pretransplant characteristics of SPK recipients (n = 39) and DM1 KTX-LR/living unrelated (LUR) recipients (KTX-LR/LUR, n = 20). In individuals who had multiple transplants, only pretransplant data from the first transplant was used. As all characteristics of KTX-LR/LUR recipients were the same, they were grouped for comparison with SPK. Pretransplant blood pressure (BP), body mass index, (BMI), hemoglobin A1c (A1c), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TG), serum creatinine, type and duration of dialysis, and duration of diabetes were compared between the two groups. Mean age at time of transplantation was 41 +/- 1 years (mean +/- SEM) for SPK versus 39 +/- 2 years for KTX-LR/LUR (P = NS). Pretransplant BP, BMI, duration of diabetes, TC, HDL, LDL, TG, and lipid agent use were not different between the groups. Pretransplant A1c was 7.8 +/- 0.3% for SPK recipients and 8.3 +/- 0.5% for KTX-LR/LUR recipients (P = NS). Pretransplant serum creatinine was higher in KTX-LR/LUR compared to SPK (7.9 +/- 0.6 mg/dL versus 5.4 +/- 0.5 mg/dL; P =.01). Except for serum creatinine, there were no significant differences in traditional CVD risk factors pretransplant. However, factors posttransplant in addition to better glucose control with SPK may still be different between SPK and KTX-LR/LUR groups

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Overexpression of both RAR and RXR restores AP-1 repression in ovarian adenocarcinoma cells resistant to retinoic acid-dependent growth inhibition

Retinoids including retinoic acid (RA) have been demonstrated to be effective growth inhibitors of a number of human cancer cell lines including ovarian adenocarcinoma cells. To begin to determine the mechanism of action by which RA inhibits the growth of ovarian carcinoma cells, we have examined AP-1 activity in two representative cell lines: CaOV-3 a RA-sensitive cell line and SK-OV-3 a RA-resistant cell line. AP-1 activity was found to be inhibited by 50% upon RA treatment of the RA-sensitive cells while there was no change in AP-1 activity following RA treatment of the RA-resistant cells. Maximal inhibition of AP-1 activity could be achieved in the RA-resistant SK-OV-3 cells by overexpression of any one of the three retinoic acid receptor (RAR) subtypes in conjunction with retinoid X receptor (RXR) α. This inhibition of AP-1 activity was nearly comparable to that of the RA-sensitive cells. A similar change in AP-1 complex formation in vitro has also been observed. These results suggest that one mechanism by which RA inhibits growth of RA-sensitive ovarian carcinoma cells is by repressing AP-1 activity. Moreover, in the RA-resistant cells the RAR/RXR signalling pathway leading to inhibition of AP-1 activity is impaired however overexpression of one of the RAR subtypes along with RXRα is sufficient to restore this pathway