Chrysiasis: Gold Aggregates Around a Nevus and Osteoma Cutis.

ABSTRACT: Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis.

Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

Mycoplasma genitalium prevalence, co-infection and macrolide resistance-associated mutations in Southern Vietnam.

Mycoplasma genitalium is an emerging sexually transmitted infection, with increasing rates of macrolide resistance and some ways of treatments being recommended by many countries. This study aimed to investigate the prevalence of M. genitalium infection, M. genitalium co-infection with other sexually transmitted organisms, and the frequency of macrolide antibiotic resistance genotypes identified in urethral specimens collected from male and urethral, vaginal and cervical specimens from female who visited the STIs clinic of HCMC Hospital of Dermato-Venereology, Vietnam. The results obtained positive samples for C. trachomatis was 8.46%, N. gonorrhoeae was 6.28%, and M. genitalium was 5.95%. Fifty-five out of 90 M. genitalium samples were found to have mutations in the 23S rRNA gene associated with macrolide resistance (61.11%). M. genitalium/C. trachomatis co-infection was 6.19%, and M. genitalium/N. gonorrhoeae was 1.22%. The percentage of M. genitalium carrying the macrolide resistance mutant gene co-infected with C. trachomatis accounted for 37.50%. The high prevalence of the M. genitalium mutations associated with macrolide resistance showed the importance of M. genitalium testing.

The effect of vasoactive agents on post-pressure hyperemia.

The cutaneous hyperemic response following the release of direct pressure occlusion lasts much longer than the short-term hyperemia that occurs after proximal arterial occlusion. Post-pressure hyperemia may be an important mechanism to prevent pressure induced injury to the skin. The role of vasoactive mediators in modulating post-pressure hyperemia is unknown. In an effort to better understand this phenomenon, we performed an initial study using microdialysis infusion to measure the effect of several known mediators of vascular response on post-pressure hyperemia. A vise clamp was used to apply direct occlusive pressure to a laser Doppler sensor on the skin surface overlying the microdialysis fiber. Skin blood flow was measured continuously pre, during and post-occlusion while infusing the vasoactive substance or control phosphate buffer. Angiotensin II, Calcitonin gene related peptide and histamine had minimal effect on post pressure blood flow. Conversely, prostaglandin E1, prostaglandin E2, and L-NAME diminished the early phase of the post-occlusion hyperemic response. Perhaps the most profound effect we observed was the decrease in post-occlusive blood flow due to administration of epinephrine, dopamine and prostaglandin F2alpha. In contrast, adenosine and caffeine augmented blood flow post occlusion. In this initial survey study, we have demonstrated differential effects of various vascular mediators on the post-pressure hyperemic phenomenon. Our findings may lead to the development of agents to prevent pressure sores by augmenting the skin blood flow response to locally applied pressure.

Temperature Changes during Implant Osteotomy Preparations in Human Cadaver Tibiae Comparing MIS® Straight Drills with Densah® Burs.

(1) Background: Several studies showed a sustained temperature of 47 °C or 50 °C for one minute resulted in vascular stasis and bone resorption with only limited bone regrowth over a 3-4-week healing period. The purpose of the present study was to evaluate the temperature changes (ΔΤ) that occur during the preparation of dental implant osteotomies using MIS® straight drills versus Densah® burs in a clockwise (cutting) drilling protocol. (2) Methods: Two hundred forty (240) osteotomies of two different systems' drills were prepared at 6 mm depth at 800, 1000, and 1200 revolutions per minute (RPM), in fresh, unembalmed tibiae, obtained by a female cadaver. ΔΤ was calculated by subtracting the baseline temperature on the tibial surface, from the maximum temperature-inside the osteotomy (ΔT = Tmax - Tbase). The variables were evaluated both for their individual and for their synergistic effect on ΔΤ with the use of one-, two-, three- and four-way interactions; (3) Results: An independent and a three-way interaction (drill design, drill width, and RPM) was found in all three RPM for the Densah® burs and at 1000 RPM for the MIS® straight drills. As Densah® burs diameter increased, ΔΤ decreased. The aforementioned pattern was seen only at 1000 RPM for the MIS® straight drills. The usage of drills 20 times more than the implant manufacturers' recommendation did not significantly affect the ΔΤ. A stereoscopic examination of the specimens confirmed the findings. (4) Conclusions: The independent and synergistic effect of drills' diameter, design and RPM had a significant effect on ΔΤ in human tibiae, which never exceeded the critical threshold of 47 °C.

Rumdul (Sphaerocoryne affinis) Antioxidant Activity and Its Potential for Parkinson's Disease Treatment.

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by progressive deterioration of motor function and loss of dopaminergic neurons in the substantia nigra. Although PD is more common in people over 60 years old, people with young-onset PD tend to increase recently. Up to now, there is no cure for PD; therapies mainly focus on reducing symptoms and improving patient quality of life. Thus, the requirement of exploring new medications is needed. There is a strong relationship between oxidative stress and PD. Therefore, antioxidant compounds have been considered as a novel therapy for PD. In this study, we indicated a new potential candidate for PD treatment, rumdul fruit (Sphaerocoryne affinis-a member of the Annonaceae family), due to evaluating its activities on the fly model of Parkinson. Our experimental results showed that rumdul fruit water extract (RFWE) has a strong antioxidant capacity with IC50 value in DPPH assay which was 85.62 ± 1.05 µg/mL. The use of RFWE at concentrations of 3, 6, and 12 mg/mL could strongly ameliorate the locomotor disabilities and dopaminergic neuron degeneration. Although the RFWE at high concentrations like 12 mg/mL and 18 mg/mL could induce some side effects on fly development and viability, our data strongly demonstrated that RFWE effectively rescued PD phenotypes on the fly model. Although component in the plant extract, as well as the molecular mechanism helping to recover the phenotype, has not been elucidated yet, the research contributed strong scientific evidence for further research on applying rumdul as a novel natural source for PD treatment.

Skin blood flow abnormalities in diabetic dermopathy.

BACKGROUND: Diabetic dermopathy is the most common specific cutaneous finding in diabetes. OBJECTIVE: Using laser Doppler technology, we tested the hypothesis that diabetic dermopathy arises from abnormal local skin blood flow. METHODS: We measured cutaneous blood flow in patients with type 1 diabetes without dermopathy and compared values with those in a control group of patients with type 1 diabetes without diabetic dermopathy and in a nondiabetic group. We measured at 3 separate sites on the pretibial area on the legs of each participant, at dermopathy lesions, and at a number of standard sites on the upper and lower extremities. RESULTS: We studied 25 patients with diabetes and diabetic dermopathy, average age 51 ± 2 years, mean duration of diabetes 28 ± 3 years. In all, 58 patients with type 1 diabetes without diabetic dermopathy served as control patients, average age 41 ± 2 years, mean duration of diabetes 23 ± 2 years. There were 67 nondiabetic control subjects, average age 47 ± 3 years. The patients with diabetic dermopathy showed a marked reduction in skin blood flow at 35°C at normal-appearing skin areas on the pretibial surface of the legs (1.1 ± 0.1 mL/min/100 g) compared with 1.7 ± 0.1 mL/min/100 g (P = .01) in the type 1 diabetic control group and 2.1 ± 0.3 mL/min/100 g (P < .01) in the nondiabetic group. The dermopathy lesions themselves showed markedly higher blood flow: 2.5 ± 0.3 mL/min/100 g. LIMITATIONS: Our diabetic dermopathy patients were somewhat older than the control type 1 diabetes subjects, but were of comparable age to the nondiabetic subjects. CONCLUSIONS: These results suggest that patients susceptible to diabetic dermopathy have a functional abnormality in blood flow leading to this scarring process.

Cerebrospinal fluid cytokine, chemokine, and SARS-CoV-2 antibody profiles in children with neuropsychiatric symptoms associated with COVID-19.

BACKGROUND: Neuropsychiatric symptoms and CSF cytokine, chemokine, and SARS-COV-2 antibody profiles are unknown in pediatric patients with COVID-19 or multisystem inflammatory syndrome (MIS-C), (NP-COVID-19). METHODS: Children at a single pediatric institution quaternary referral center with laboratory-confirmed COVID-19 or MIS-C and neuropsychiatric symptoms were included in this retrospective case series. Clinical symptoms, ancillary testing data, treatments and outcomes are described. Multiplexed electrochemiluminescence assays for cytokines, chemokines and SARS-CoV-2 antibodies were tested in the CSF NP-COVID-19 patients compared to five controls and were analyzed using the Student's t-test. RESULTS: Three of five NP-COVID-19 patients had psychiatric symptoms, and two patients had encephalopathy and seizures. All patients had full or near resolution of neuropsychiatric symptoms by discharge. One patient received intravenous steroids for treatment for psychiatric symptoms; 3/5 other patients received immunotherapy for MIS-C, including IVIG, high-dose steroids, anakinra, and tocilizumab. Pro-inflammatory chemokines, including MIG, MPC, MIP-1ß, and TARC were significantly elevated in NP-COVID-19 patients compared to controls. Two of five patients had elevated CSF neurofilament light chain. CSF SARS-CoV-2 antibody titers to the full-length spike, receptor binding domain and N-terminal domain were significantly elevated. SARS-CoV-2 antibody titers strongly correlated with pro-inflammatory chemokines/cytokines, including IL-1ß, IL-2, IL-8, TNF-α, and IFN-γ (P≤0.05 for all). CONCLUSIONS: A spectrum of neuropsychiatric clinical manifestations can occur in children with SARS-CoV-2 infection. CSF pro-inflammatory chemokines and SARS-CoV-2 antibodies may serve as biomarkers of SARS-CoV-2 mediated NP-COVID-19. Additional study is required to understand the pathophysiologic mechanisms of neuroinflammation in children with COVID-19 and MIS-C.

The time to offer treatments for COVID-19.

Background: COVID-19 has several overlapping phases. Treatments to date have focused on the late stage of disease in hospital. Yet, the pandemic is by propagated by the viral phase in out-patients. The current public health strategy relies solely on vaccines to prevent disease.Methods: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results.Results: As of 2/15/2021, we found 111 publications reporting findings on 14 classes of agents, and 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care. Remdesivir and high titer convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries.Expert Opinion: Vaccines and antibodies are highly antigen specific, and new SARS-Cov-2 variants are appearing. We call on public health authorities to authorize treatments with known low-risk and possible benefit for outpatients in parallel with universal vaccination.

The Importance of Understanding the Stages of COVID-19 in Treatment and Trials.

COVID-19, caused by SARS-CoV-2, continues to be a major health problem since its first description in Wuhan, China, in December 2019. Multiple drugs have been tried to date in the treatment of COVID-19. Critical to treatment of COVID-19 and advancing therapeutics is an appreciation of the multiple stages of this disease and the importance of timing for investigation and use of various agents. We considered articles related to COVID-19 indexed on PubMed published January 1, 2020-November 15, 2020, and considered papers on the medRxiv preprint server. We identified relevant stages of COVID-19 including three periods: pre-exposure, incubation, and detectable viral replication; and five phases: the viral symptom phase, the early inflammatory phase, the secondary infection phase, the multisystem inflammatory phase, and the tail phase. This common terminology should serve as a framework to guide when COVID-19 therapeutics being studied or currently in use is likely to provide benefit rather than harm.

Skin blood flow in patients with stage 5 chronic kidney disease on hemodialysis.

We have shown previously that skin perfusion is reduced in patients with diabetes mellitus (DM). Patients with diabetes and with chronic kidney disease (CKD) stage 5 were having advanced microangiopathy. In this cross-sectional study, we measured skin blood flow in DM and non-DM patients on dialysis to assess whether any differences exist in skin perfusion in those 2 groups of patients. A total of 25 patients with DM (aged 59.9 +/- 2.2 years) and 24 patients with non-DM CKD stage 5 (44.6 +/- 2.9 years) on hemodialysis (HD) were studied. Ten healthy subjects (37 +/- 4.3 years) were used as a control group. Skin blood flow (SBF) was measured using Vasamedic Model 403B laser Doppler device (Vasamedics Inc., St. Paul, MN) in a standardized way at the plantar and dorsal surface of the finger and toe and at the pretibial surface of the leg at 2 different local skin temperatures of 35 degrees C and 44 degrees C. Laboratory biochemical data were collected at the time of SBF study. The SBF measured at 35 degrees C was lower in the patients with DM on dialysis as compared with healthy subjects and non-DM dialysis patients. The SBF response to the increase in temperature of the probe to 44 degrees C was 70% to 80% lower in DM patients as compared with healthy subjects and non-DM patients. However, non-DM subjects who displayed SBF similar to control subjects at 35 degrees C, had impaired response in SBF at 44 degrees C as well. Patients with lower serum albumin exhibited lower SBF even after adjustment for age. SBF is impaired in patients with stage 5 CKD on HD, particularly in those with DM as a cause of CKD. SBF negatively correlated with age and albumin (nutritional status) in DM and non-DM patients with stage 5 CKD on HD. Measurement of SBF can be useful in the evaluation of vasculopathy in CKD population and can potentially be used for assessment of vascular response during specific clinical intervention.