Mucosal CCL28 Chemokine Improves Protection against Genital Herpes through Mobilization of Antiviral Effector Memory CCR10+CD44+ CD62L-CD8+ T Cells and Memory CCR10+B220+CD27+ B Cells into the Infected Vaginal Mucosa.

Four major mucosal-associated chemokines, CCL25, CCL28, CXCL14, and CXCL17, play an important role in protecting mucosal surfaces from infectious pathogens. However, their role in protection against genital herpes remains to be fully explored. The CCL28 is a chemoattractant for the CCR10 receptor-expressing immune cells and is produced homeostatically in the human vaginal mucosa (VM). In this study, we investigated the role of the CCL28/CCR10 chemokine axis in mobilizing protective antiviral B and T cell subsets into the VM site of herpes infection. We report a significant increase in the frequencies of HSV-specific memory CCR10+CD44+CD8+ T cells, expressing high levels of CCR10, in herpes-infected asymptomatic (ASYMP) women compared with symptomatic women. Similarly, a significant increase in the CCL28 chemokine (a ligand of CCR10), was detected in the VM of herpes-infected ASYMP C57BL/6 mice, associated with the mobilization of high frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and memory CCR10+B220+CD27+ B cells in the VM of HSV-infected ASYMP mice. Inversely, compared with wild-type C57BL/6 mice, the CCL28 knockout (CCL28-/-) mice (1) appeared to be more susceptible to intravaginal infection and reinfection with HSV type 2, and (2) exhibited a significant decrease in the frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and of memory CD27+B220+ B cells in the infected VM. These findings suggest a critical role of the CCL28/CCR10 chemokine axis in the mobilization of antiviral memory B and T cells within the VM to protect against genital herpes infection and disease.

A multi-epitope/CXCL11 prime/pull coronavirus mucosal vaccine boosts the frequency and the function of lung-resident memory CD4+ and CD8+ T cells and enhanced protection against COVID-19-like symptoms and death caused by SARS-CoV-2 infection.

IMPORTANCE: Although the current rate of SARS-CoV-2 infections has decreased significantly, COVID-19 still ranks very high as a cause of death worldwide. As of October 2023, the weekly mortality rate is still at 600 deaths in the United States alone, which surpasses even the worst mortality rates recorded for influenza. Thus, the long-term outlook of COVID-19 is still a serious concern outlining the need for the next-generation vaccine. This study found that a prime/pull coronavirus vaccine strategy increased the frequency of functional SARS-CoV-2-specific CD4+ and CD8+ memory T cells in the lungs of SARS-CoV-2-infected triple transgenic HLA-DR*0101/HLA-A*0201/hACE2 mouse model, thereby resulting in low viral titer and reduced COVID-19-like symptoms.

Synthesis and activity of ß-carboline antimalarials targeting the Plasmodium falciparum heat shock 90 protein.

A collection of ß-carbolines based on the natural product harmine, a compound known to target the heat shock 90 protein of Plasmodium falciparum, was synthesized and tested for antimalarial activity and potential toxicity. Several of these novel compounds display promising bioactivity, providing a new potential therapeutic with a mode of action that differs versus any currently available clinical treatment.

The Impact of a Culturally Meaningful Storytelling Intervention on Stigma and Attitudes About Mental Health Treatment.

ABSTRACT: The fear of being devalued or discriminated against is a salient deterrent to seeking mental health care, especially in communities of color where racial stigma also impacts mental health and perceptions of service utilization. To address this issue, our research team partnered with This Is My Brave Inc to develop and evaluate a virtual storytelling intervention to highlight and amplify the voices of Black and Brown Americans living with mental illness and/or addiction. We utilized a pretest-posttest survey design administered electronically to viewers of the series ( n = 100 Black, indigenous, people of color and n = 144 non-Hispanic White). Results indicated that postintervention, scores on public stigma and perceived discrimination measures were significantly reduced. We identified significant interaction effects, such that Black, indigenous, people of color viewers showed a greater rate of improvement on outcomes. This study provides strong preliminary evidence of the impact of a culturally meaningful virtual approach to addressing stigma and improving attitudes about mental health treatment.

Non-Invasive Treatment of Basal Cell Carcinoma: Photodynamic Therapy Following Curettage.

BACKGROUND: To investigate the effectiveness, safety, patient satisfaction, and cosmetic outcome of Methyl Aminolevulinate-Photodynamic Therapy (MAL-PDT) following curettage in order to make recommendations for its use in dermatology practices. METHODS: A retrospective chart review of patients who received MAL-PDT following curettage for the indication of basal cell carcinoma (BCC) between 2009 and 2016 at a single private clinic in Ontario, Canada. Two hundred and seventy-eight patients with 352 BCC lesions were included, consisting of 44.2% males (n=123) and 55.8% females (n=155) with a mean age of 57.24 years. The primary outcome measurement consisted of the cure rate. Secondary outcome measurements included side effects, patient satisfaction, and cosmetic outcome, as reported in the medical charts. RESULTS: The overall cure rate was 90.3% (n=318). After controlling for age, sex, and lesion type, nasal lesions were approximately 2.82 (95% CI: 1.24-6.40, P=0.01) times more likely to experience a recurrence. 18.3% of patients (n=51) reported side effects, the most common being burning (n=19). Of those who expressed satisfaction, 100% (n=25) reported being happy. Of lesions with cosmetic data, 90.3% displayed a good response (n=149). CONCLUSION: MAL-PDT following curettage is an effective and safe treatment option for BCC lesions with a good cosmetic outcome and suggested high patient satisfaction. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7133.

Rationale and Design of a Study to Test the Effect of Personal Protective Aids on Hypertension and Diabetes in People Living With High Levels of Air Pollution-Study Protocol.

BACKGROUND: Air pollution is the largest environmental cause of disease and premature death in the world today, disproportionally affecting low- and middle-income countries (LMIC) such as India. Studies have shown that exposure to particulate matter <2.5 µm (PM2.5) can contribute to cardiovascular disease and increase mortality. We hypothesise that the use of personal protective aids (home indoor air purifiers/N95 masks) can decrease systolic blood pressure (SBP) in people with hypertension and decrease fasting blood glucose levels (FBG) in those with diabetes. METHOD: This is a prospective randomised crossover study in Dalkhola, India-an area of high ambient PM2.5 levels. Participants between 18-70 years of age with hypertension (n=128) and diabetes (n=33) will be invited to participate in the study. They will be randomised to either an intervention or control arm for 4 weeks, after which they will cross over to the other arm following a 2-week washout period. The intervention will consist of using an indoor air purifier at night and N95 mask when outdoors. The control period will involve using an identical air purifier and N95 mask with the filter removed (sham filtration). Participants and outcome assessors will be blinded to study arm assignment. OUTCOME EVALUATION: The primary outcome of the study is the absolute reduction in SBP among people with hypertension and absolute reduction in FBG among people with diabetes. DISCUSSION: This is the first randomised controlled trial to evaluate the use of personal protective aids as a therapeutic measure in people with hypertension and diabetes exposed to high levels of PM2.5. Given the high burden of air pollution in LMIC, there is an urgent need for adaptation measures targeting people at high risk for mortality from this exposure. The results of our study will demonstrate whether personal protective aids can be a viable adaptation measure for people living with hypertension and diabetes in areas with a high burden of air pollution. TRIAL REGISTRATION: This is clinicaltrials.gov Identifier: NCT04854187.

Preliminary effectiveness study of the Cope Notes digital mental Health program.

BACKGROUND: Cope Notes is a subscription-based EMI that uses Short Message Service (SMS) technology to deliver daily text messages that promote hope, reduce stigma, and encourage coping and the use of positive psychology strategies. AIM: We aimed to evaluate the preliminary effectiveness of Cope Notes, a brief ecological momentary intervention (EMI). METHODS: We conducted a longitudinal study where participants (N = 64) completed measures of depression, anxiety, perceived stress, coping, emotional intelligence, label avoidance, attitudes towards treatment-seeking, and readiness for change before the intervention, 1 month post-intervention, and 2 months post-intervention. This study includes mixed repeated measures ANOVAs to analyze over time. RESULTS: Findings show that participants with severe depression experienced a significant decrease in anxiety and depressive symptoms, and perceived stress (p < .001) and showed a significant increase in emotional intelligence at 1 month post-intervention. Participants with mild to moderate depression experienced a significant increase in overall coping and problem-focused coping. CONCLUSIONS: While further investigation of Cope Notes' feasibility and acceptability is warranted, these findings support that the Cope Notes EMI holds promise as a low-cost, impactful mental health solution for populations with limited access to care and those experiencing self-stigma preventing help-seeking.

Paired analysis of ED efficiency for low-acuity children treated by PAs and pediatricians.

OBJECTIVE: To determine if there was a clinically important difference (15 minutes or more) in length of stay (LOS) for low-acuity pediatric ED patients treated by PAs compared with those treated by pediatricians. METHODS: Between July 2017 and February 2020, shifts were identified that had shared PA and pediatrician staffing in the low-acuity care area for a large, urban ED. LOS was collected for every patient during the 6 hours of overlap for each shift. Using a paired analysis, we calculated the difference in mean LOS for these shifts. RESULTS: Mean shift LOS for children seen by PAs (160.1 minutes, SD: 48.6) was 10.1 minutes longer (95% CI: 6.1, 14.1) than mean shift LOS for children seen by pediatricians (150 minutes, SD: 47.3). CONCLUSIONS: No clinically important difference in LOS was found for low-acuity children treated by PAs compared with those treated by pediatricians in a large, urban ED.

DNA Strand Displacement Driven by Host-Guest Interactions.

Base-pair-driven toehold-mediated strand displacement (BP-TMSD) is a fundamental concept employed for constructing DNA machines and networks with a gamut of applications─from theranostics to computational devices. To broaden the toolbox of dynamic DNA chemistry, herein, we introduce a synthetic surrogate termed host-guest-driven toehold-mediated strand displacement (HG-TMSD) that utilizes bioorthogonal, cucurbit[7]uril (CB[7]) interactions with guest-linked input sequences. Since control of the strand-displacement process is salient, we demonstrate how HG-TMSD can be finely modulated via changes to the structure of the input sequence (including synthetic guest head-group and/or linker length). Further, for a given input sequence, competing small-molecule guests can serve as effective regulators (with fine and coarse control) of HG-TMSD. To show integration into functional devices, we have incorporated HG-TMSD into machines that control enzyme activity and layered reactions that detect specific microRNA.

CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas.

Natural killer (NK) cells are a promising cellular immunotherapy for cancer. Cytokine-induced memory-like (ML) NK cells differentiate after activation with interleukin-12 (IL-12), IL-15, and IL-18, exhibit potent antitumor responses, and safely induce complete remissions in patients with leukemia. However, many cancers are not fully recognized via NK cell receptors. Chimeric antigen receptors (CARs) have been used to enhance tumor-specific recognition by effector lymphocytes. We hypothesized that ML differentiation and CAR engineering would result in complementary improvements in NK cell responses against NK-resistant cancers. To test this idea, peripheral blood ML NK cells were modified to express an anti-CD19 CAR (19-CAR-ML), which displayed significantly increased interferon γ production, degranulation, and specific killing against NK-resistant lymphoma lines and primary targets compared with nonspecific control CAR-ML NK cells or conventional CAR NK cells. The 19-CAR and ML responses were synergistic and CAR specific and required immunoreceptor tyrosine-based activation motif signaling. Furthermore, 19-CAR-ML NK cells generated from lymphoma patients exhibited improved responses against their autologous lymphomas. 19-CAR-ML NK cells controlled lymphoma burden in vivo and improved survival in human xenograft models. Thus, CAR engineering of ML NK cells enhanced responses against resistant cancers and warrants further investigation, with the potential to broaden ML NK cell recognition against a variety of NK cell-resistant tumors.

Pernio and early SARS-CoV-2 variants: natural history of a prospective cohort and the role of interferon.

Cases of new-onset pernio and recurrences in our cohort align tightly with trends in mean 7-day COVID-19 positivity in Wisconsin and mean temperature in Madison, Wisconsin by month.

Feasibility of Diagnosing Initial Orthostatic Hypotension Using a Continuous Blood Pressure Device in Geriatric Rehabilitation Inpatients: RESORT.

BACKGROUND: Initial orthostatic hypotension (IOH) is highly prevalent in older adults and may interfere with the ability to regain function after acute hospitalization. IOH assessment requires a non-invasive, beat-to-beat continuous blood pressure device, which is not widely used in geriatric rehabilitation. Our aim was to test the feasibility of diagnosing IOH using a continuous blood pressure device in geriatric rehabilitation inpatients. METHODS: Geriatric rehabilitation inpatients of the REStORing Health of Acutely Unwell AdulTs (RESORT) cohort admitted to a tertiary hospital were randomly selected to undergo continuous blood pressure monitoring (Finapres) for 5 min in the supine position and 3 min of standing or sitting when unable to stand. Interventions to warm hands and adjusting the cuff pressure sizes were attempted if no signal was obtained or an error message occurred. RESULTS: Of 37 randomly selected inpatients, 29 {55.2% female; mean age 82.8 (standard deviation [SD]) 6.6 years} agreed to the continuous blood pressure measurement. Successful measurements were achieved in 20 out of 29 inpatients, two after hand warming. Patients with unsuccessful measurements were likely to be older (mean age 87.2 [SD] 4.4 years, p = 0.03), have cerebrovascular disease (p = 0.006), lower body mass index (p = 0.012), and a lower short physical performance battery score (p = 0.039). Eight out of 20 patients had IOH. CONCLUSION: The number of unsuccessful continuous blood pressure measurements was high in a population with high IOH prevalence despite multiple interventions to establish a signal. Future research should focus on improving the efficiency of continuous blood pressure devices in hospitalized patients with unsuccessful signals.

Prospective, Single-arm, Split-face Pain Management Evaluation of Nitrous Oxide System During Micro-Focused Ultrasound With Visualization.

BACKGROUND: Although micro-focused ultrasound with visualization (MFU-V) has great cosmetic results, patients can be hesitant or decline the treatment due to the pain experienced during the treatment. The primary objective is to assess the efficacy of pain management of the nitrous oxide system during MFU-V treatment. The secondary objectives include patient satisfaction and efficacy on reducing facial laxity and improving aesthetic appearance. PATIENTS AND METHODS: A prospective, single-arm, split-face, open-label study. Ten patients were treated with MFU-V without use of a self-administered nitrous oxide system on the right side of the face, followed by use of the nitrous oxide system on the left. A patient-reported Visual Analog Pain Intensity Scale was used to assess pain on the right and left sides at 3 different treatment time points. Patient satisfaction was measured using a 5-point Likert scale and efficacy was measured using the Investigator GAIS and the Facial Laxity Score. RESULTS: Clinically significant differences were seen between pain ratings for the treated and untreated sides at 2 of the 3 time points. 100.0% of patients (n=9) who had completed the study were very satisfied (55.6%) or somewhat satisfied (44.4%). Five patients (55.6%) were scored as Improved on the GAIS and 4 patients (44.4%) were scored as Much Improved. 90.00% (n=9) of patients had moderate lower face and neck laxity prior to treatment, compared with 11.11% (n=1) and 22.22% (n=2) with moderate laxity at follow-up. CONCLUSION: The nitrous oxide system provides clinically significant pain reduction, increases patient satisfaction, and improves cosmetic results of MFU-V treatment. J Drugs Dermatol. 2022;21(11):1228-1234. doi:10.36849/JDD.7030.

Early-onset hypertension associated with extensive cutaneous capillary malformations harboring postzygotic variants in GNAQ and GNA11.

BACKGROUND AND OBJECTIVES: Cutaneous capillary malformations (CMs) describe a group of vascular birthmarks with heterogeneous presentations. CMs may present as an isolated finding or with other associations, including glaucoma and leptomeningeal angiomatosis (i.e., Sturge-Weber syndrome) or pigmentary birthmarks (i.e., phakomatosis pigmentovascularis). The use of targeted genetic sequencing has revealed that postzygotic somatic variations in GNAQ and GNA11 at codon 183 are associated with CMs. We report five patients with early-onset hypertension and discuss possible pathogenesis of hypertension. METHODS: Twenty-nine patients with CMs, confirmed GNAQ/11 postzygotic variants, and documented past medical history were identified from a multi-institutional vascular anomalies study. Early-onset hypertension was defined as hypertension before the age of 55 years. Clinical data were reviewed for evidence of hypertension, such as documentation of diagnosis or elevated blood pressure measurements. RESULTS: Five of the 29 patients identified as having GNAQ/11 postzygotic variants had documented early-onset hypertension. Three individuals harbored a GNAQ p.R183Q variant, and two individuals harbored a GNA11 p.R183C variant. All individuals had extensive cutaneous CMs involving the trunk and covering 9%-56% of their body surface area. The median age of hypertension diagnosis was 15 years (range 11-24 years), with three individuals having renal abnormalities on imaging. CONCLUSIONS: Early-onset hypertension is associated with extensive CMs harboring somatic variations in GNAQ/11. Here, we expand on the GNAQ/11 phenotype and hypothesize potential mechanisms driving hypertension. We recommend serial blood pressure measurements in patients with extensive CMs on the trunk and extremities to screen for early-onset hypertension.

Novel findings and expansion of phenotype in a mosaic RASopathy caused by somatic KRAS variants.

Mosaic KRAS variants and other RASopathy genes cause oculoectodermal, encephalo-cranio-cutaneous lipomatosis, and Schimmelpenning-Feuerstein-Mims syndromes, and a spectrum of vascular malformations, overgrowth and other associated anomalies, the latter of which are only recently being characterized. We describe eight individuals in total (six unreported cases and two previously reported cases) with somatic KRAS variants and variably associated features. Given the findings of somatic overgrowth (in seven individuals) and vascular or lymphatic malformations (in eight individuals), we suggest mosaic RASopathies (mosaic KRAS variants) be considered in the differential diagnosis for individuals presenting with asymmetric overgrowth and lymphatic or vascular anomalies. We expand the association with embryonal tumors, including the third report of embryonal rhabdomyosarcoma, as well as novel findings of Wilms tumor and nephroblastomatosis in two individuals. Rare or novel findings in our series include the presence of epilepsy, polycystic kidneys, and T-cell deficiency in one individual, and multifocal lytic bone lesions in two individuals. Finally, we describe the first use of targeted therapy with a MEK inhibitor for an individual with a mosaic KRAS variant. The purposes of this report are to expand the phenotypic spectrum of mosaic KRAS-related disorders, and to propose possible mechanisms of pathogenesis, and surveillance of its associated findings.

Prevalence of initial orthostatic hypotension in older adults: a systematic review and meta-analysis.

BACKGROUND: Initial orthostatic hypotension (OH) is a clinical syndrome of exaggerated transient orthostasis associated with higher risks of falls, frailty and syncope in older adults. OBJECTIVE: To provide a prevalence estimate of initial OH in adults aged 65 years or older. METHODS: Literature search of MEDLINE (from 1946), Embase (from 1947) and Cochrane Central Register of Controlled Trials was performed until 6 December 2019, using the terms 'initial orthostatic hypotension', 'postural hypotension' and 'older adults'. Articles were included if published in English and participants were 65 years or older. Random effects models were used for pooled analysis. RESULTS: Of 5,136 articles screened, 13 articles (10 cross-sectional; 3 longitudinal) reporting data of 5,465 individuals (54.5% female) from the general (n = 4,157), geriatric outpatient (n = 1,136), institutionalised (n = 55) and mixed (n = 117) population were included. Blood pressure was measured continuously and intermittently in 11 and 2 studies, respectively. Pooled prevalence of continuously measured initial OH was 29.0% (95% CI: 22.1-36.9%, I2 = 94.6%); 27.8% in the general population (95% CI: 17.9-40.5%, I2 = 96.1%), 35.2% in geriatric outpatients (95% CI: 24.2-48.1%, I2 = 95.3%), 10.0% in institutionalised individuals (95% CI: 2.4-33.1%, I2 = 0%) and 21.4% in the mixed population (95% CI: 7.0-49.6, I2 = 0%). Pooled prevalence of intermittently measured initial OH was 5.6% (95% CI: 1.5-18.9%, I2 = 81.1%); 1.0% in the general population (95% CI: 0.0-23.9%, I2 = 0%) and 7.7% in geriatric outpatients (95% CI: 1.8-27.0%, I2 = 86.7%). CONCLUSION: The prevalence of initial OH is high in older adults, especially in geriatric outpatients. Proper assessment of initial OH requires continuous blood pressure measurements.

Light-based treatment of pediatric port-wine birthmarks.

Port-wine birthmarks (PWBs) are progressive vascular malformations with significant disfigurement and psychosocial morbidity; early light-based treatment has shown improved outcomes in the pediatric population. Somatic mosaic mutations underly the progressive nature of PWBs and explain the significant differences in response and heterogeneity of vessel architecture in the pediatric population when compared to the adult cohort. Here, we summarize a review of pediatric specific literature on the various light-based treatment modalities, including pulsed dye laser, near-infrared lasers, and intense pulsed light, providing the various indications, tips, advantages, and disadvantages for the pediatric dermatologist.

Initiation of fibrosis in the integrin Αvß6 knockout mice.

We previously demonstrated that ß6 knockout mice showed impaired wound repair in corneal debridement and keratectomy wounds. In the current investigation, we continued our examination of integrin αvß6 in order to determine if it was required for the initiation of wound healing in a corneal wound model that normally heals in a fibrotic manner. A full-thickness corneal incision was made in C57BL/6 J wild type (WT) and C57BL/6-Itgb6 KO (ß6-/-) mice. The mice were observed at 3, 7, 14, and 28 days post-incision. The morphology of corneal restoration was observed in tissue sections stained with hemotoxilin and eosin (H&E). In addition, indirect-immunofluorescence (IF) was performed on sections and/or whole mounts to evaluate the immunolocalization of α-smooth muscle actin (SMA) and thrombospondin-1 (TSP-1). H&E staining revealed that the corneas in ß6-/- mice healed slower than those in WT mice, with an obvious delay in the restoration of the stromal matrix and epithelium. In sections at 3 and 7 days, SMA and TSP-1 were greatly reduced in the ß6-/- mice as compared to WT, but peaked at 28 days after incision. Whole mount SMA IF results were consistent with those from sections. Therefore, the initiation of fibrosis was inhibited by the lack of αvß6; however, there appeared to be an alternate mechanism that initiated fibrosis 7-14 days later. Localization of TSP-1 correlated with expression of SMA whether wound healing was delayed or initiated immediately after wounding.

Significant Variation in the Detection Rates of Proximal Serrated Polyps Among Academic Gastroenterologists, Community Gastroenterologists, and Colorectal Surgeons in a Single Tertiary Care Center.

INTRODUCTION: Recent studies have demonstrated that the protective effect of colonoscopy against colorectal cancer is lower in the proximal colon. Proximal serrated polyps, including sessile serrated adenomas and proximal hyperplastic polyps, can be frequently missed and pose a risk of interval cancers. AIM: To investigate the overall adenoma detection rate (ADR) and the proximal serrated polyp detection rate (PSPDR) among academic gastroenterologists, community gastroenterologists, and colorectal surgeons from a single institution, all of whom have received formal training in colonoscopy during their fellowship. METHODS: All complete screening colonoscopies for patients aged 50 or older with a good to excellent bowel preparation performed by different endoscopists at Medstar Washington Hospital Center (Washington, DC) from July 2015 to December 2017 were reviewed. Pathology reports of the resected polyps were manually reviewed. RESULTS: A total of 2850 screening colonoscopies meeting the inclusion criteria were performed by 18 endoscopists (6 academic, 7 community, and 5 colorectal surgeons). There was no significant difference in the mean ADR among the three groups of endoscopists: academic gastroenterologists, community gastroenterologists, and colorectal surgeons (40.3% vs 36.0% vs 39.6%, respectively). However, academic gastroenterologists had a significantly higher PSPDR compared to community gastroenterologists or colorectal surgeons (12.3% vs 5.4% vs 4.5%, respectively, ANOVA p = 0.006). CONCLUSION: Our novel data show that academic gastroenterologists had a significantly higher PSPDR compared to community gastroenterologists or colorectal surgeons despite a comparable overall ADR among the three groups. PSPDR may be considered as an important quality indicator for colonoscopy, apart from ADR.

Low-Dose and Standard Overnight and Low Dose-Two Day Dexamethasone Suppression Tests in Patients with Mild and/or Episodic Hypercortisolism.

We previously reported on the lack of utility of the 1 mg overnight dexamethasone (DEX) test in mild and/or periodic Cushing's syndrome, as most patients with the condition suppressed to 1 mg DEX. It is possible that a lower dose of DEX as part of an overnight DEX test might be able to distinguish between mild and/or periodic Cushing's syndrome and those without the condition. The objective of the current study is to determine the sensitivity and specificity of a 0.25 mg overnight DEX suppression test, the standard 1 mg overnight DEX suppression test, and the two-day low-dose (Liddle test) DEX suppression test with and without correction for DEX levels in patients evaluated for mild and/or periodic Cushing's syndrome. Thirty patients determined to have Cushing's syndrome by biochemical testing and 14 patients determined not to have the condition had the 0.25 mg and standard 1 mg overnight DEX suppression test and the two-day low-dose DEX suppression tests. Our results show that morning serum cortisol and cortisol/DEX ratios following an overnight dexamethasone suppression test were similar in patients with Cushing's syndrome and those not having Cushing's syndrome. However, a morning cortisol value above 7.6 µg/dl following a dose of DEX of 0.25 mg was found in 12 patients with Cushing's syndrome and none in those not having Cushing's syndrome, suggesting that a high cortisol value after this low dose of dexamethasone can indicate that further testing for Cushing's syndrome is warranted. Our data suggest that the traditional 1 mg overnight or the 2 mg/2 day DEX suppression testing should no longer be used as a screening test in patients who could have mild and/or periodic Cushing's syndrome, while the 0.25 mg dose of DEX may pick up some patients with mild Cushing's syndrome.