Professional stigma towards clients with methamphetamine use disorder - a qualitative study.

Background: Methamphetamine use disorder (MUD) is associated with poor health outcomes. Pharmacists play a role in delivery of substance use treatment, with several studies having examined their attitudes to people with opioid use disorder, but little is known about their attitude towards people with MUD. This study aimed to explore pharmacists' perspectives on the provision of services to clients with MUD. Methods: A convenience sampling strategy was used to recruit community pharmacists across Sydney, Australia. Semi structured interviews examined views and ideas of pharmacists surrounding the treatment and management of MUD, followed by coding of transcribed interview data by all members of the research team. Results: Nineteen pharmacists completed the interviews. The main theme identified was stigma held by healthcare professionals. The almost unanimous perception amongst pharmacists was fear and apprehension towards people with MUD, including underlying assumptions of criminality, misinformation regarding people with MUD, and lack of education and knowledge surrounding MUD. Conclusion: A substantial amount of stigma towards people with MUD was found in this study. Negative attitudes by healthcare professionals can perpetuate healthcare disparities and impede the accessibility of future treatment programs for people with MUD. Appropriate educational interventions on MUD for pharmacists are needed.

Nuclear Tau, p53 and Pin1 Regulate PARN-Mediated Deadenylation and Gene Expression.

While nuclear tau plays a role in DNA damage response (DDR) and chromosome relaxation, the mechanisms behind these functions are not fully understood. Here, we show that tau forms complex(es) with factors involved in nuclear mRNA processing such as tumor suppressor p53 and poly(A)-specific ribonuclease (PARN) deadenylase. Tau induces PARN activity in different cellular models during DDR, and this activation is further increased by p53 and inhibited by tau phosphorylation at residues implicated in neurological disorders. Tau's binding factor Pin1, a mitotic regulator overexpressed in cancer and depleted in Alzheimer's disease (AD), also plays a role in the activation of nuclear deadenylation. Tau, Pin1 and PARN target the expression of mRNAs deregulated in AD and/or cancer. Our findings identify novel biological roles of tau and toxic effects of hyperphosphorylated-tau. We propose a model in which factors involved in cancer and AD regulate gene expression by interactions with the mRNA processing machinery, affecting the transcriptome and suggesting insights into alternative mechanisms for the initiation and/or developments of these diseases.

Normal and Pathological Tau Uptake Mediated by M1/M3 Muscarinic Receptors Promotes Opposite Neuronal Changes.

The microtubule associated protein tau is mainly found in the cell's cytosol but recently it was also shown in the extracellular space. In neurodegenerative diseases, like Alzheimer's disease (AD), pathological tau spreads from neuron to neuron enhancing neurodegeneration. Here, we show that HEK293 cells and neurons in culture uptake extracellular normal and pathological Tau. Muscarinic receptor antagonists atropine and pirenzepine block 80% this uptake. CHO cells do not express these receptors therefore cannot uptake tau, unless transfected with M1 and/or M3 receptor. These results strongly suggest that muscarinic receptors mediate this process. Uptake of normal tau in neurons enhances neuronal process formation but a pseudophosphorylated form of tau (pathological human tau, PH-Tau) disrupts them and accumulates in the somatodendritic compartment. AD hyperphosphorylated tau (AD P-Tau) has similar effects as PH-Tau on cultured neurons. Addition of either PH-Tau or AD P-tau to neuronal cultures induced microglial activation. In conclusion, uptake of extracellular tau is mediated by muscarinic receptors with opposite effects: normal tau stabilizes neurites; whereas pathological tau disrupts this process leading to neurodegeneration.

An Unusual Cause of Headache and Fatigue in a Division 1 Collegiate Athlete.

Variegate porphyria (VP) is an autosomal dominant disorder of porphyrin metabolism. We report a case of a 21-year-old male collegiate athlete who complained of recurrent headache and fatigue. Extensive testing after initial presentation failed to identify a cause. Months later, his grandmother was diagnosed with VP after being hospitalized; hence, he was tested. He was positive for a heterozygous missense mutation, R168H, in one protoporphyrinogen oxidase allele. This case highlights a rare disorder of heme synthesis that should be considered in the differential diagnosis of exertional fatigue and headaches in athletes. When other more common causes of fatigue and/or headache are unable to be identified, a more focused history and examination may lead to a more unusual but crucial diagnosis. To our knowledge, there are no reported cases of this condition in Division I collegiate athletes.

The effect of sonophoresis on topical anesthesia: a pilot project.

The dental anesthesia sonophoresis device (DASD) is a novel device that is intended to reduce the discomfort associated with intraoral mucosa needle puncture. The DASD produces ultrasonic energy that provides a sonophoretic effect on the oral mucosa, generating microchannels through the lipids between the keratinized cells that make up the stratum corneum. Once the topical anesthetic has permeated the stratum corneum, it quickly diffuses through the soft tissue, desensitizing the nerve endings and reducing the perception of pain caused by needle penetration. The aim of this study is to evaluate whether topical anesthesia applied using the DASD will reduce the discomfort of the needle puncture when compared to the control device. A split-mouth model, using 50 healthy subjects with puncture site at the maxillary canine vestibule, was used for this study. Subjects received a needle puncture on both sides of the mouth. Prior to the needle puncture, there was randomized application of 5% lidocaine with the DASD and a control device. Subjects rated their discomfort after needle punctures utilizing the visual analog scale pain scoring system. There was no statistically significant difference in the pain perception using the DASD versus the control device.

Comparison of inter-twin concordance in symptoms of temporomandibular disorders: a preliminary investigation in an adolescent twin population.

There is controversy as to the genetic contribution to the pathogenesis of temporo-mandibular disorders (TMD). Several reports reveal a marked familial aggregation in the signs and symptoms of TMD, while others do not. Therefore, our goal was to investigate the hypothesis using a sophisticated research design, which was a well-known genetic survey inter-twin concordance assessment in the symptoms of TMD. This study is the first step to survey TMD symptoms of a twin group in junior and high schools as a preliminary trial. The 63 twins were asked to participate in this study in junior and senior high schools affiliated with the University of Tokyo, Japan, schools which kept ten twins in each grade for the purpose of several genetic survey programs. After excluding incomplete filling out of questionnaire sheets and data from male-female pairs, 43 monozygotic (MZ) (15.3+/-1.7 yrs, male/female = 17/26 pairs) and nine dyzygotic (DZ) (15.2+/-1.8 yrs, male/female = 6/3 pairs) twins were studied. Outcomes consisted of a prevalidated 14-item self-administered questionnaire, which assessed proband- and pair-wise concordance levels in the MZ and DZ twins. These results demonstrated that the MZ twins had a higher tendency of inter-twin concordance than DZ twins in terms of jaw pain in wide mouth opening (proband-wise concordance = 66.7% in MZ, 0% in DZ), difficulty in mouth opening (20% in MZ, 0% in DZ) and difficulty in mouth closing (50.0% in MZ, 33.3% in DZ), while there was no significant difference between the MZ and DZ concordance levels in other general health-related and behavior-related items, except toothache. However, the pair-wise concordance rates of jaw pain in wide mouth opening and difficulty in mouth opening in the MZ twins were not significantly higher compared to the DZ rate. Possibly, a genetic factor contributed to the pathogenesis of TMD in an adolescent population. The sample size needs to be increased, and there are plans to survey the next sample in the same schools.