ABSTRACT
Left ventricular masses are rare entities that often require surgical excision when diagnosed due to the risk of embolization. We report 2 separate patients presenting with evidence of cerebral embolization both of whom were diagnosed with isolated left ventricular masses and underwent surgical excision through a robot-assisted approach. Microscopic pathology revealed a myxoma and hemangioma, respectively. Both cases demonstrate that left ventricular masses can be feasibly excised through a robot-assisted minithoracotomy approach.
Subject(s)
Heart Neoplasms , Hemangioma , Myxoma , Robotics , Humans , Heart Ventricles/diagnostic imaging , Heart Ventricles/surgery , Heart Ventricles/pathology , Thoracotomy , Myxoma/diagnostic imaging , Myxoma/surgery , Heart Neoplasms/diagnostic imaging , Heart Neoplasms/surgery , Hemangioma/diagnostic imaging , Hemangioma/surgery , Hemangioma/pathologyABSTRACT
BACKGROUND: COVID-19 pandemic had tremendously affected all the aspects of human life during the past 3 years. In this study, we focused on kidney transplant patients' course from the COVID-19 diagnosis, immunosuppressive medication modification, hospitalization, and COVID-19 complications and how the COVID-19 infection affected the kidney and patients' quality of life during the hospitalization and after the discharge. MATERIAL AND METHOD: A retrospective analysis of a prospectively collected database of all kidney transplants adult patients who had a positive COVID-19 PCR from 1 January 2020 to 30 December 2022, and had a history of kidney transplant at the SUNY Upstate Medical Hospital was done to identify the cases. RESULTS: 188 patients met the inclusion criteria and were included in the study. Based on the immunosuppressive regimen modification during COVID-19 infection, patients divided into two groups; in 143 (76%) patients, the immunosuppressive medication was reduced, and in 45 (24%) of patients, the immunosuppressive regimen continued as before during the COVID-19 infection. The mean time from the transplant to the diagnosis of COVID-19 was 67 months in the group we reduced the IM regimen, and 77 months in the group without changes in IM regimen. The mean recipients' age was 50.7 ± 12.9 years in the group we reduced the IM regimen, and 51.8 ± 16.4 years in the group without changes in IM regimen (P = 0.64). The vaccination rate against COVID-19 with at least 2 doses of either the CDC recommended Moderna or Pfizer vaccines was 80.2% in the group we reduced the IM regimen, and 84.8% in the group without changes in IM regimen (P = 0.55). The hospitalization rate due to COVID-19 related symptoms was 22.4% % in the group we reduced the IM regimen, and 35.5% in the group without changes in IM regimen (P = 0.12). However, the ICU admission rate was higher in the group we reduced the IM regimen, but the difference was not significant (26.5% Vs.6.25%, P = 0.12). 6 episodes of biopsy-proven rejection in the group with IM reduction was observed, which were 3 episodes of acute antibody-mediated rejections (ABMR) and 3 episodes of acute T-Cell-mediated rejections (TCMR), and 3 episodes in the group without any change in IM regimen, which were 2 episodes of ABMR and 1 episode of TCMR (P = 0.51). No significant difference was mentioned in the eGFR and serum creatinine after the comparison between the groups after 12 months of follow up. 124 patients responded to the post-COVID-19 questionnaires and were included in the data analysis. The response rate was 66%. Fatigue and exertion were the most reported symptom with a 43.9% prevalence. CONCLUSIONS: We found that immunosuppressive regimen minimization did not impact the kidney function in the long-term and it might be a helpful strategy to minimize the effect of COVID-19 infection on patients' condition during the hospital stay. With all the treatments, vaccinations, and precautions, still some patients did not achieve the complete recovery compared to their pre-COVID-19 health status. Fatigue was the main reported symptom amongst all the reported symptoms.
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Purpose: Existing and emerging visual acuity methods like dynamic and dichoptic presentation, preferential looking and eye tracking promise to afford better and earlier assessment in children with and without amblyopia so we propose methods needed to easily evaluate and compare their metrics. Subjects and Methods: Patients older than 8 years with treated amblyopia and superb vision (logMAR -0.1 to -0.3) normals performed timed, patched eETDRS with Sloan matching card at 3.00 m and PDI Check dichoptic near rivalry dynamic test to demonstrate test re-Test and compared disparate acuity with intraclass correlation (ICC) and Bland Altman 95% limits of agreement (LOA) to generate a simple method of qualifying acuity test matching. Results: 26 amblyopic patients and 11 superb-vision normals performed eETDRS retest, PDI Check retest and combined ICC of 0.98, 0.60 and 0.27, respectively, and Bland Altman LOA of 0.24, 2.06 and 2.28 logMAR. The time to test one eye with eETDRS had median (interquartile range; IQR) duration of 280 (205 to 346) seconds, while the PDI Check autostereoscopic dichoptic for both eyes only took 39 (30 to 47) seconds. Optimum ICC and LOA for visual acuity comparison should be >0.95 and <0.3 logMAR, whereas "good" ICC and should be 0.75-0.89 ICC and 1.0-1.49 logMAR LOA. Conclusion: Superb vision subjects (logMAR < -0.1) and treated amblyopic patients confirmed optimum comparable eETDRS, and fair test re-Test PDI Check but suppression on near dichoptic testing confirmed disparity compared to optimized eETDRS distance acuity.
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BACKGROUND: The costimulatory inhibitor Belatacept (Bela) has been shown to be an effective alternative in several clinical situations, including chronic antibody-mediated rejection, calcineurin toxicity, and de novo alloantibody formation. To further explore the usefulness of Belatacept under various clinical scenarios, we performed a retrospective analysis of a prospective database of all recipients who had a BPAR diagnosis of CAMR and were converted to a Belatacept maintenance immunosuppression regimen after kidney transplantation. MATERIAL AND METHOD: We conducted a retrospective analysis of a prospectively collected database of all kidney transplants adult patients at SUNY Upstate Medical Hospital from 1 January 2013 to 31 December 2021. Our inclusion criteria were the patients who have been diagnosed with CAMR according to their renal biopsy based on the 2013 Banff criteria. The primary objective was to compare the kidney viability and function using GFR between the two interest groups and finally compare the outcomes. RESULTS: A total of 48 patients met our inclusion criteria based on the kidney biopsy result, which showed chronic antibody-mediated graft rejection (CAMR). Nineteen patients (39.6%) were converted to the Belatacept, and we continued the previous immunosuppression regimen in 29 patients (60.4%). The mean time from the transplant date to the diagnosis of CAMR was 1385 days in the Belatacept group and 914 days for the non-Belatacept group (P = 0.15). The mean GFR comparison at each time point between the groups did not show a significant difference, and Belatacept did not show superiority compared to the standard immunosuppression regimen in terms of kidney function preservation. 1 (5.2%) patient from the Belatacept group and 1 (3.4%) patient from the non-Belatacept group had a biopsy-proven acute rejection (BPAR) after CAMR confirmation, and it was comparable (P = 0.76). De novo synthesis of the DSA rate was 12.5% in the Belatacept group and 15% In the non-Belatacept group, which was comparable. (P = 0.90). The patient survival rate was 100% in both groups. CONCLUSIONS: We conclude that compared to the standard Tacrolimus/MMF/Prednisone regimen, Belatacept did not significantly benefit in preserving the GFR in long-term follow-ups and stabilizing the DSA production, which is one of the main factors resulting in chronic graft failure.
Subject(s)
Immunosuppressive Agents , Kidney Transplantation , Adult , Humans , Abatacept/therapeutic use , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Retrospective Studies , Isoantibodies , Graft Rejection , Graft Survival , Transplant RecipientsABSTRACT
Aim: To evaluate the use of low-dose naltrexone (LDN) as a broad-spectrum analgesic. Methods: Retrospective cohort study from a single pain management practice using data from 2014 to 2020. Thirty-six patients using LDN for ≥2 months were matched to 42 controls. Pain scores were assessed at initial visit and at most recent/final documented visit using a 10-point scale. Results: Cases reported significantly greater pain reduction (-37.8%) than controls (-4.3%; p < 0.001). Whole sample multivariate modeling predicts 33% pain reduction with LDN, with number needed to treat (for 50% pain reduction) of 3.2. Patients with neuropathic pain appeared to benefit even more than those with 'nociceptive'/inflammatory pain. Conclusion: LDN is effective in a variety of chronic pain states, likely mediated by TLR-4 antagonism.
Naltrexone has historically been used to treat various substance use disorders, but recent discoveries have sparked interest in using low-dose naltrexone (LDN) to manage chronic pain. This study compared pain levels reported by patients before and after at least 2 months of LDN treatment to those reported by patients with the same painful diseases, who did not take LDN. Overall, patients who took LDN reported significantly more pain relief than patients who did not take LDN. How LDN alleviates pain seems complex, but apparently involves an anti-inflammatory effect on cells in the brain and spinal cord. LDN is extraordinarily safe, with no known risks (unlike most standard pain medications), and should be studied more in the treatment of chronic pain.
Subject(s)
Chronic Pain , Naltrexone , Analgesics, Opioid/therapeutic use , Chronic Pain/drug therapy , Humans , Naltrexone/pharmacology , Naltrexone/therapeutic use , Narcotic Antagonists/pharmacology , Narcotic Antagonists/therapeutic use , Retrospective StudiesABSTRACT
BACKGROUND: Patient-reported outcomes and satisfaction following short length of stay (LoS) after total knee arthroplasty (TKA) in the Australian regional context remain unexplored. This study reports complications, outcomes and satisfaction of patients discharged from an enhanced recovery protocol (ERP), 6 weeks after TKA in a regional hospital. METHODS: Prospective recruitment occurred between 2018 and 2019. Demographics, intraoperative data, complications and emergency department (ED) presentations were retrieved from hospital records. Complications were graded for severity using a published scale. Knee range of motion (ROM), timed up-and-go (TUG), 6-min walk test (6MWT) and Oxford Knee Scores (OKS) were assessed preoperatively and 6 weeks postoperatively. Patient satisfaction was assessed via questionnaire at the postoperative follow-up. RESULTS: One hundred patients/117 primary TKAs were prospectively included. Median LoS was 2 days (interquartile range 1-3 days) with 74.4% and 88.4% of patients satisfied with their knee and LoS, at 6 weeks respectively. Twenty-seven patients presented to the ED a total of 37 times with complication severity of Grade III or less, and 10 patients were readmitted. Significant improvements in objective and subjective outcomes were observed, however only change in median OKS exceeded the minimal clinically important difference (MCID) threshold. CONCLUSION: An enhanced recovery protocol after TKA in a regional hospital can achieve a median LoS of 2 days without compromising patient-reported outcomes and objective functional measures, whilst maintaining a high level of patient satisfaction with both the surgery and LoS. Further work is required to better optimize management of largely low-grade complications in this patient population.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Arthroplasty, Replacement, Knee/adverse effects , Australia/epidemiology , Hospitals, Public , Humans , Length of Stay , Osteoarthritis, Knee/surgery , Patient Reported Outcome Measures , Prospective StudiesABSTRACT
BACKGROUND: Handheld devices can automatically give an estimate of refraction. The established method for refraction comparison using spherical equivalent (M) and J0, J45 vector transformations by Bland-Altman analysis is too complex for non-eye doctors involved with vision screening and remote vision clinics. Therefore, a simpler comparison technique was developed. METHODS: Based on the spectacle limit to resolve grade A 1 logMAR, B 3 logMAR and C 6 logMAR blur, J0, J45, and M are combined into the Alaska Blind Child Discovery (ABCD) composite ellipsoid GRADE system. Pediatric eye patients had confirmatory examination after dry refraction with three portable autorefractors: Plusoptix, 2WIN and Retinomax. The refractions were then compared using both Bland-Altman and ABCD composite. Performance to detect AAPOS amblyopia risk factors was also assessed. RESULTS: A total of 202 children, mean age seven years, 28% high spectacle need and 43% AAPOS 2013 amblyopia risk factors showed high correlation with cycloplegic refraction (intraclass correlation 0.49 to 0.90) for sphere, J0 and J45 spectacle components. Plusoptix had more (10%) inconclusives due to patients out-of-range. The Retinomax was unable to screen some younger children and was less reliable for sphere but gave more precise astigmatism estimates. The proportion of autorefractions expected to give GRADE A/B high-need patients acuity improvement to 20/40 would be 41% for Plusoptix, 39% for 2WIN and 65% for Retinomax. Sensitivity/specificity for amblyopia risk factor detection was 80%/83% for Plusoptix, 72%/88% for 2WIN and 84%/73% for Retinomax. CONCLUSION: The simplified spectacle comparison resembled Bland-Altman and could assist lay vision screeners and non-eye doctors attempting remote spectacle donation worldwide.
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With the rapid shift to telemedicine brought on by the COVID-19 pandemic, physiatrists must get accustomed to the new technology and learn how to optimize their evaluations. For those practitioners managing patients with acquired brain injuries, which include stroke and traumatic brain injury, this can seem a daunting task given potential physical and cognitive barriers. However, as the authors discuss techniques to optimize visits, the aim is to illustrate how telehealth appointments can not only be comparable to in-person examinations but also may help increase outreach, compliance, and even satisfaction among this unique population.
Subject(s)
Brain Injuries/physiopathology , Brain Injuries/therapy , Telemedicine/methods , COVID-19/epidemiology , Health Services Accessibility , Humans , Pandemics , Patient Compliance , Patient Satisfaction , Physical Examination , SARS-CoV-2ABSTRACT
BACKGROUND: Portable autorefractors can estimate refractive error in remote locations, but sphero-cylinder comparison and donated-spectacle dispensing are not yet simple. METHODS: Normal astigmats determined best corrected acuity, then degraded 1 logMAR (Grade A), 3 logMAR (Grade B), and 6 logMAR (Grade C) to determine limits of astigmatism axis and power at these levels. The cylindrical refraction was vector transformed with J0 on the abscissa and J45 on the ordinate. RESULTS: Ten subjects produced multiple refractions at the interfaces of Grades A, B, and C representing ovals on the J0 and J45 coordinates. When rotated, the vertical axis represented 45° or 135°, the horizontal long axis was 1.6× the short axis. The size of the ovals positively correlated with cylinder power. Given a target refraction, the comparability of a candidate lens was demonstrated on our interactive database yielding a simple A, B, C, or worse grade for cylinder, spherical equivalent, and pupillary diameter. CONCLUSIONS/RELEVANCE: Inputting a remote autorefraction, pupillary diameter and age as target and a donated spectacle as the candidate with a "B" grade similarity would be expected to attain 20/40 acuity (3 logMAR degrade) if best corrected visual acuity was 20/20. This practical Excel database could facilitate widespread remote lay dispensing of the cylinder as well as spherical spectacles. The grade similarity can also compare refracting tools such as photoscreeners and hand-held autorefractors. CLINICAL TRIALS REGISTRY: NCT04297969.
ABSTRACT
In an effort to reduce hospital length of stay (LoS) following total knee arthroplasty (TKA), patient management strategies have evolved over time. The aims of this study were threefold: first, to quantify the reduction in LoS for TKA in a regional hospital; second, to identify the patient, surgical and management factors associated with hospital LoS; and lastly, to assess the change in complications incidence and hospital readmission as a function of LoS. A retrospective chart review was conducted on a consecutive series of primary and revision TKAs from January 2012 to March 2018. Factors describing patient demographics, as well as preoperative, intraoperative, surgical, and postoperative management, were extracted from paper and electronic medical records by a team of reviewers. Multivariate linear regression was performed to assess the association between these factors and LoS. In total, 362 procedures were included, which were reduced to 329 admissions once simultaneous bilateral procedures were taken into account. Median LoS reduced significantly (p = 0.001) from 6 to 2 days over the period of review. A stepwise regression analysis identified patient characteristics (age, gender, comorbidities, discharge barriers), perioperative management (anesthesia type), surgical characteristics (approach, alignment method), and postoperative management (mobilization timing, postoperative narcotic use, complication prior to discharge) as factors explaining 58.3% of the variance in LoS. Representation to emergency (6%) and hospital readmission (3%) remained low for the reviewed period. Efforts to reduce hospital LoS following TKA within a regional hospital setting can be achieved over time without significant increases in the rate or severity of complications or representation to acute care and subsequent readmission. The findings establish the role of patient, surgical and management factors in the context of agreed discharge criteria between care providers.
Subject(s)
Arthroplasty, Replacement, Knee , Length of Stay , Osteoarthritis, Knee/surgery , Aged , Arthroplasty, Replacement, Knee/adverse effects , Female , Hospitals/statistics & numerical data , Humans , Incidence , Male , Middle Aged , Patient Readmission/statistics & numerical data , Pilot Projects , Postoperative Complications/epidemiology , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: A low-detail, glowing fixation device was added to GoCheck Kids (GCK) photoscreener in the hope of unmasking hyperopia and amblyopia risk factors (ARF). METHODS: Pediatric eye patients were screened by GCK and 2WIN photoscreeners, and Retinomax autorefractor before being compared to AAPOS ARFs. RESULTS: Screening was attempted by 131 children who then had school bus accommodation-relaxing skiascopy (SBA-RS) before cycloplegic examination. By 2013 AAPOS uniform guidelines, sensitivity/specificity for GCK was 87%/68%, for 2WIN 87%/71% and for Retinomax 79%/68%. Detection of amblyopia had sensitivity/specificity by GCK of 78%/63%, for 2WIN 79%/65% and for Retinomax 77%/68%. Inconclusive screens were seven for GCK, six for 2WIN and 13 for Retinomax. Mean hyperopia for GCK (+2.49±0.74 D) was similar to cycloplegic refraction (+2.93±0.72 D) and SBA-RS (+2.80±0.82 D) while GCK was slightly more than Retinomax (+1.59±0.93 D, p=0.13) but significantly more than 2WIN (+1.02±0.49 D, p<0.01). CONCLUSION: GCK, 2WIN and Retinomax had similar validity detecting uniform amblyopia risk factors and amblyopia itself. The nondetailed glow fixation device allowed GCK to uncover substantial hyperopia while the detailed flashing fixation devices on 2WIN and Retinomax seemed to stimulate accommodation in some hyperopic children. CLINICAL TRIALS REGISTRY: NCT04297969. Data Access: http://www.abcd-vision.org/references/GCK%20glow%202WIN%20deidentify.pdf. PRÉCIS: A glow fixation device on a smart phone photoscreener allowed robust detection of hyperopia.
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BACKGROUND: A near vision game has been developed for the autostereoscopic screen of the Nintendo 3DS console. Ease of use and time for testing by non-English-speaking patients was not known. METHODS: Adult and pediatric patients in a remote Burma clinic were compared with US military staff with each performing conventional near acuity, Stereo Fly, and Ishihara color in addition to PDI Check game, so results could be correlated and timed. RESULTS: Seventeen Burma adults (aged 19-58), 20 Burma children (aged 7-15), and 14 US military staff (aged 21-36) completed the testing. Conventional testing correlated with PDI Check for stereo (Pâ<â0.001), acuity oculo dexter (Pâ<â0.01), acuity oculo sinister (Pâ<â0.01). For visual acuity and stereopsis, the intraclass coefficient was 0.55 [95% confidence interval (CI) 0.28-0.72] and 0.62 (95% CI 0.41-0.77) respectively, but with few color deficient cases color was 0.30 (95% CI -0.05 to 0.60). The time in seconds to complete near vision testing with PDI Check (172â±â27, overall; 198â±â34, Burma; 99â±â20, military) was significantly (25%â±â18%) briefer than conventional testing (226â±â31, overall; 270â±â34, Burma; 126â±â20, military). The Burma patients took significantly longer than the military staff (234â±â25 vs 112â±â14, Pâ<â0.01). Time for Burma children did not differ from Burma adults for PDI (109â±â47 vs 217â±â54, Pâ=â0.42) and for conventional testing (266â±â51 vs 275â±â52, Pâ=â0.80). CONCLUSIONS: Non-English-speaking Burma children and adults were able to reliably perform 3 types of near vision testing with a Nintendo 3DS game 25% quicker than the 2 to 3 minutes for conventional methods. They were slower than experienced US military staff adults.
Subject(s)
Depth Perception/physiology , Video Games , Vision Disorders/diagnosis , Vision Screening/instrumentation , Visual Acuity , Adolescent , Adult , Child , Equipment Design , Female , Humans , Male , Middle Aged , Myanmar/epidemiology , Prevalence , Prospective Studies , Reproducibility of Results , Vision Disorders/epidemiology , Young AdultABSTRACT
The ability to appropriately respond to environmental conditions is critical for the survival of simple microbes and for development of complex multicellular organisms. Sensing and responding to a given environmental condition requires the integration of numerous signals through one or more signal transduction pathways. This leads to changes in gene expression, and potentially post-translational modifications, that favour growth in the given environment. In the fungus Candida albicans, an important opportunistic pathogen, environmental pH has profound effects on morphology and proper adaptation to extracellular pH is critical for pathogenesis. Here, we demonstrate that the Rim101/PacC pH-sensing pathway acts in parallel to Crz1, via calcineurin, to adapt to alkaline pH. We also show that the Rim101 pathway acts in parallel to Crz2, independent of calcineurin, to adapt to high lithium concentrations and to repress filamentation at acidic pH. Our studies also revealed a novel requirement for Crz1, Crz2 and calcineurin for growth at acidic pH. From these studies, we propose that the Crz1 homologue Crz2 is calcineurin-independent, but like Crz1, acts in parallel to promote specific Rim101-dependent processes. These results establish and begin to dissect the complex interactions between important signal transduction pathways in C. albicans, which are critical for virulence.
Subject(s)
Adaptation, Physiological , Calcineurin/metabolism , Candida albicans/physiology , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Signal Transduction , Calcineurin/genetics , Candida albicans/genetics , Candida albicans/growth & development , Candida albicans/metabolism , Fungal Proteins/genetics , Humans , Hydrogen-Ion Concentration , MutationABSTRACT
Candida albicans is a commensal fungus of mucosal surfaces that can cause disease in susceptible hosts. One aspect of the success of C. albicans as both a commensal and a pathogen is its ability to adapt to diverse environmental conditions, including dramatic variations in environmental pH. The response to a neutral-to-alkaline pH change is controlled by the Rim101 signal transduction pathway. In neutral-to-alkaline environments, the zinc finger transcription factor Rim101 is activated by the proteolytic removal of an inhibitory C-terminal domain. Upon activation, Rim101 acts to induce alkaline response gene expression and repress acidic response gene expression. Previously, recombinant Rim101 was shown to directly bind to the alkaline-pH-induced gene PHR1. Here, we demonstrate that endogenous Rim101 also directly binds to the alkaline-pH-repressed gene PHR2. Furthermore, we find that of the three putative binding sites, only the -124 site and, to a lesser extent, the -51 site play a role in vivo. In C. albicans, the predicted Rim101 binding site was thought to be CCAAGAA, divergent from the GCCAAG site defined in Aspergillus nidulans and Saccharomyces cerevisiae. Our results suggest that the Rim101 binding site in C. albicans is GCCAAGAA, but slight variations are tolerated in a context-dependent fashion. Finally, our data suggest that Rim101 activity is governed not only by proteolytic processing but also by an additional mechanism not previously described.
Subject(s)
Candida albicans/physiology , DNA-Binding Proteins/physiology , Fungal Proteins/metabolism , Fungal Proteins/physiology , Membrane Glycoproteins/metabolism , Binding Sites/genetics , Binding, Competitive , Candida albicans/genetics , Candida albicans/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Electrophoretic Mobility Shift Assay , Fungal Proteins/genetics , Hydrogen-Ion Concentration , Membrane Glycoproteins/genetics , Mutation/genetics , Promoter Regions, Genetic/genetics , Protein Binding , Protein Processing, Post-TranslationalABSTRACT
The human pathogen Candida albicans grows and colonizes sites that can vary markedly in pH. The pH response in C. albicans is governed in part by the Rim101p pathway. In Saccharomyces cerevisiae, Rim101p promotes alkaline responses by repressing expression of NRG1, itself a transcriptional repressor. Our studies reveal that in C. albicans, Rim101p-mediated alkaline adaptation is not through repression of CaNRG1. Furthermore, our studies suggest that Rim101p and Nrg1p act in parallel pathways to regulate hyphal morphogenesis, an important contributor to virulence. To determine the wild-type C. albicans transcriptional response to acidic and alkaline pH, we utilized microarrays and identified 514 pH-responsive genes. Of these, several genes involved in iron acquisition were upregulated at pH 8, suggesting that alkaline pH induces iron starvation. Microarray analysis of rim101-/- cells indicated that Rim101p does not govern transcriptional responses at acidic pH, but does regulate a subset of transcriptional responses at alkaline pH, including the iron acquisition genes. We found that rim101-/- cells are sensitive to iron starvation, which suggests that one important aspect of the Rim101p-dependent alkaline pH response is to adapt to iron starvation conditions.
Subject(s)
Adaptation, Physiological , Candida albicans/physiology , DNA-Binding Proteins/physiology , Fungal Proteins/physiology , Gene Expression Profiling , Gene Expression Regulation, Fungal , Oligonucleotide Array Sequence Analysis , Candida albicans/genetics , DNA-Binding Proteins/genetics , Fungal Proteins/genetics , Gene Deletion , Genes, Fungal , Hydrogen-Ion Concentration , Hyphae/growth & development , Iron/metabolism , Regulon , Repressor Proteins/physiology , VirulenceABSTRACT
Candida albicans is an important commensal of mucosal surfaces that is also an opportunistic pathogen. This organism colonizes a wide range of host sites that differ in pH; thus, it must respond appropriately to this environmental stress to survive. The ability to respond to neutral-to-alkaline pHs is governed in part by the RIM101 signal transduction pathway. Here we describe the analysis of C. albicans Rim13p, a homolog of the Rim13p/PalB calpain-like protease member of the RIM101/pacC pathway from Saccharomyces cerevisiae and Aspergillus nidulans, respectively. RIM13, like other members of the RIM101 pathway, is required for alkaline pH-induced filamentation and growth under extreme alkaline conditions. Further, our studies suggest that the RIM101 pathway promotes pH-independent responses, including resistance to high concentrations of lithium and to the drug hygromycin B. RIM13 encodes a calpain-like protease, and we found that Rim101p undergoes a Rim13p-dependent C-terminal proteolytic processing event at neutral-to-alkaline pHs, similar to that reported for S. cerevisiae Rim101p and A. nidulans PacC. However, we present evidence that suggests that C. albicans Rim101p undergoes a novel processing event at acidic pHs that has not been reported in either S. cerevisiae or A. nidulans. Thus, our results provide a framework to understand how the C. albicans Rim101p processing pathway promotes alkaline pH-independent processes.