Onychomycosis, the Active Invasion of a Normal Nail Unit by a Dermatophytic Versus the Colonization of an Existing Abnormal Nail Unit by Environmental Fungus.

Onychomycosis was described by early investigators as the presence of an abnormal nail unit and a member of the order Mycota, producing the abnormality. This interpretation has caused more than 50 years of confusion in the dermatologic literature. Unquestionably, the clinician sees more abnormal toenails than fingernails, and investigators have described a multitude of fungi as the cause of the clinically abnormal toenail. In 2010, developmental scientists proved, what we have long recognized, that there is no bilateral symmetry in living organisms and, therefore, one sole is different from the other. This causes a gait asymmetry, coupled with the pressure the closed shoe exerts on toenails while walking. This produces a series of abnormalities, which are clinically identical to what has been described for dermatophytic onychomycosis. These are fungus free and result in toenail niches. These toenail abnormalities were recently described as the asymmetric gait nail unit syndrome (AGNUS). It is possible that environmental fungi can colonize these toenail niches and, therefore, were described by investigators as a new onychomycosis entity In the normal host, onychomycosis should be only used to describe the active invasion of the nail bed (NB) corneocytes by a dermatophyte, as seen in dermatophytic onychomycosis. Dermatophytes only affect those hosts who have inherited the dermatophytosis susceptibility gene, transmitted as an autosomal dominant trait. In studies encompassing 3,000 abnormal toenails, only 27%-30% were found as dermatophyte culture positive, 25% were negative and the rest environmental fungi were recovered.

Effects of Periodic Intensive Insulin Therapy: An Updated Review.

BACKGROUND: Traditional insulin treatment for diabetes mellitus with insulin administered subcutaneously yields nonpulsatile plasma insulin concentrations that represent a fraction of normal portal vein levels. Oral hypoglycemic medications result in the same lack of pulsatile insulin response to blood glucose levels. Intensive treatments of significant complications of diabetes are not recommended due to complicated multidrug regimens, significant weight gain, and the high risk of hypoglycemic complications. Consequently, advanced complications of diabetes do not have an effective treatment option because conventional therapy is not sufficient. Intensive insulin therapy (IIT) simulates normal pancreatic function by closely matching the periodicity and amplitude of insulin secretion in healthy subjects; however, the mechanisms involved with the observed improvement are not clearly understood. OBJECTIVE: The current review aims to analyze the pathophysiology of insulin secretion, discuss current therapies for the management of diabetes, provides an updates on the recent advancements of IIT, and proposes its mechanism of action. METHODS: A literature search on PubMed, MEDLINE, Embase, and CrossRef databases was performed on multiple key words regarding the history and current variations of pulsatile and IIT for diabetes treatment. Articles reporting the physiology of insulin secretion, advantages of pulsatile insulin delivery in patients with diabetes patients, efficacy and adverse effects of current conventional insulin therapies for the management of diabetes, benefits and shortcomings of pancreas and islet transplantation, or clinical trials on patients with diabetes treated with pulsed insulin therapy or advanced IIT were included for a qualitative analysis and categorized into the following topics: mechanism of insulin secretion in normal subjects and patients with diabetes and current therapies for the management of diabetes, including oral hypoglycemic agents, insulin therapy, pancreas and islet transplantation, pulsed insulin therapy, and advances in IIT. RESULTS: Our review of the literature shows that IIT improves the resolution of diabetic ulcers, neuropathy, and nephropathy, and reduces emergency room visits. The likely mechanism responsible for this improvement is increased insulin sensitivity from adipocytes, as well as increased insulin receptor expression. CONCLUSIONS: Recent advancements show that IIT is an effective option for both type 1 diabetes mellitus and type 2 diabetes mellitus patient populations. This treatment resembles normal pancreatic function so closely that it has significantly reduced the effects of relatively common complications of diabetes in comparison to standard treatments. Thus, this new treatment is a promising advancement in the management of diabetes. (Curr Ther Res Clin Exp. 2019; 80:XXX-XXX).

Asymmetric gait nail unit syndrome: the most common worldwide toenail abnormality and onychomycosis.

Asymmetric gait nail unit syndrome (AGNUS) is the result of asymmetric shoe pressure on the toes and foot caused by ubiquitous uneven flat feet that affect the gait. The pressure produces clinical changes in the toenails, which are identical to all clinical types of dermatophyte and opportunistic onychomycosis, yet they are dermatophytes-free. AGNUS produces additional signs that make it easy to identify. Its coexistence with fungal disease has resulted in reports describing new clinical types of onychomycosis, identifying signs of drug resistance, assessing severity index, and defining complete clinical cure when taking a systemic or topical antifungal, as well as "retronychia." These signs are typically seen in the toenails of patients with AGNUS. AGNUS has a mechanical etiology and can coexist with dermatophytosis, which is a hereditary disease. AGNUS can coexist with any other disease affecting the toenails and results in greater clinical severity than each condition individually. AGNUS is and has been the most common worldwide toenail abnormality in shoe-wearing societies.