After a medical student prompted medical faculty to tell their stories of depression and related mental health issues, the author wrote this article with the aim of decreasing the stigma of mental ...illness and encouraging treatment, as needed, in the medical profession. The professional culture of the house of medicine not only mimics society in attributing stigma to people with mental health issues but may also contribute to high rates of suicide in the ranks of health care professionals by leading to a delay in seeking treatment. Acculturation accelerates in the first year of medical school such that medical students experience an increase in burnout and depressive symptoms from prematriculation levels. It follows that faculty have a responsibility to improve the learning environment. Survey data from medical faculty at the author's institution showed that depression decreased respondents' willingness to seek mental health treatment because of the stigma and issues of access to help. Faculty attitudes toward mental health issues, including reluctance to admit having such issues, may be conveyed to medical students in the hidden curriculum that teaches them to keep depression hidden. Moreover, the fear of mental disorders is manifested in licensing and privileging applications under the guise of patient safety, contributing to a culture of shame and silence. As creators and guardians of this professional culture, medical faculty and other physicians must be the ones who change it. The same faculty who play a part in causing and perpetuating stigma related to mental health issues have the power to derive and enact some of the solutions. In addition to giving voice to a personal experience of mental health issues, this article offers suggestions for normalizing moderate to severe depression as a medical disorder, decreasing the stigma of mental health issues, and encouraging faculty to seek treatment.
The microbial mats of Guerrero Negro (GN), Baja California Sur, Mexico historically were considered a simple environment, dominated by cyanobacteria and sulfate-reducing bacteria. Culture-independent ...rRNA community profiling instead revealed these microbial mats as among the most phylogenetically diverse environments known. A preliminary molecular survey of the GN mat based on only ∼1500 small subunit rRNA gene sequences discovered several new phylum-level groups in the bacterial phylogenetic domain and many previously undetected lower-level taxa. We determined an additional ∼119,000 nearly full-length sequences and 28,000 >200 nucleotide 454 reads from a 10-layer depth profile of the GN mat. With this unprecedented coverage of long sequences from one environment, we confirm the mat is phylogenetically stratified, presumably corresponding to light and geochemical gradients throughout the depth of the mat. Previous shotgun metagenomic data from the same depth profile show the same stratified pattern and suggest that metagenome properties may be predictable from rRNA gene sequences. We verify previously identified novel lineages and identify new phylogenetic diversity at lower taxonomic levels, for example, thousands of operational taxonomic units at the family-genus levels differ considerably from known sequences. The new sequences populate parts of the bacterial phylogenetic tree that previously were poorly described, but indicate that any comprehensive survey of GN diversity has only begun. Finally, we show that taxonomic conclusions are generally congruent between Sanger and 454 sequencing technologies, with the taxonomic resolution achieved dependent on the abundance of reference sequences in the relevant region of the rRNA tree of life.
Modern nautilids (Nautilus and Allonautilus) have often been studied by paleontologists to better understand the anatomy and ecology of fossil relatives. Because direct observations of these animals ...are difficult, the analysis of light stable isotopes (C, O) preserved in their shells has been employed to reveal their habitat and life history. We aim to (1) reconstruct the habitat depth of Nautilus macromphalus and (2) decipher the fraction of metabolic carbon in its shell by analyzing oxygen and carbon isotopes (delta.sup.18 O, delta.sup.13 C) in the septa of two specimens in combination with analyses of water samples from the area. Additionally, we investigate whether morphological changes during ontogeny are reflected in the isotopic values of the shells. Results reveal that the patterns of change of delta.sup.18 O and delta.sup.13 C in the septa of N. macromphalus pre- and post-hatching are consistent with previous studies. Values of delta.sup.18 O.sub.water range from 0.7 to 1.4% (VSMOW), with a maximum value coincident with a salinity maximum at ~150 m. We use the temperature and delta.sup.18 O.sub.water profiles to calculate equilibrium values of delta.sup.18 O.sub.aragonite with depth. Comparing these values with the measured delta.sup.18 O of the septa shows that the habitat depth of N. macromphalus is ~140 m pre-hatching and ~370 m post-hatching. Using delta.sup.13 C of shell carbonate and published data on metabolic carbon, the fraction of metabolic carbon is reconstructed as ~21% and 14% pre- and post-hatching, respectively. The reconstructed depth pre-hatching is slightly shallower than in N. pompilius from the Philippines and Fiji, but the post-hatching depth is similar. However, it is important to emphasize that these estimates represent average over time and space because nautilus is a mobile animal. Lastly, the changes in morphological parameters and the changes in delta.sup.13 C and delta.sup.18 O during ontogeny do not coincide except at hatching and at the onset of maturity.
Constitutive proteasomes and immunoproteasomes shape the peptide repertoire presented by major histocompatibility complex class I (MHC-I) molecules by harboring different sets of catalytically active ...subunits. Here, we present the crystal structures of constitutive proteasomes and immunoproteasomes from mouse in the presence and absence of the epoxyketone inhibitor PR-957 (ONX 0914) at 2.9 Å resolution. Based on our X-ray data, we propose a unique catalytic feature for the immunoproteasome subunit β5i/LMP7. Comparison of ligand-free and ligand-bound proteasomes reveals conformational changes in the S1 pocket of β5c/X but not β5i, thereby explaining the selectivity of PR-957 for β5i. Time-resolved structures of yeast proteasome:PR-957 complexes indicate that ligand docking to the active site occurs only via the reactive head group and the P1 side chain. Together, our results support structure-guided design of inhibitory lead structures selective for immunoproteasomes that are linked to cytokine production and diseases like cancer and autoimmune disorders.
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► First ligand structures of mouse constitutive proteasomes and immunoproteasomes are determined ► A unique hydrophilic architecture surrounds the β5i-oxyanion hole ► Structures explain the enhanced generation of MHC-I antigens by immunoproteasomes ► The mode of action and selectivity of the β5i-specific compound PR-957 is revealed
Structural insights into the molecular differences between the constitutive proteasome and the immunoproteasome explain why the immunoproteasome is more competent in producing MHC-I ligands and why it is preferentially targeted by the inhibitor PR-957.
The article "The Polarized Mind in Context: Interdisciplinary Approaches to the Psychology of Political Polarization" (van Baar & FeldmanHall, 2022) explores a crucial challenge to contemporary U.S. ...society. The article focuses on two aspects of the polarized mind: cognitive inflexibility and (exogenous) environmental factors, such as "media filter bubbles" and "biased social networks." However, there are also underlying existential-humanistic and psychodynamic factors that have been identified as elucidating the polarized mind.
Abstract Insomnia in patients with alcohol dependence has increasingly become a target of treatment due to its prevalence, persistence, and associations with relapse and suicidal thoughts, as well as ...randomized controlled studies demonstrating efficacy with behavior therapies and non-addictive medications. This article focuses on assessing and treating insomnia that persists despite 4 or more weeks of sobriety in alcohol-dependent adults. Selecting among the various options for treatment follows a comprehensive assessment of insomnia and its multifactorial causes. In addition to chronic, heavy alcohol consumption and its effects on sleep regulatory systems, contributing factors include premorbid insomnia; co-occurring medical, psychiatric, and other sleep disorders; use of other substances and medications; stress; environmental factors; and inadequate sleep hygiene. The assessment makes use of history, rating scales, and sleep diaries as well as physical, mental status, and laboratory examinations to rule out these factors. Polysomnography is indicated when another sleep disorder is suspected, such as sleep apnea or periodic limb movement disorder, or when insomnia is resistant to treatment. Sobriety remains a necessary, first-line treatment for insomnia, and most patients will have some improvement. If insomnia-specific treatment is needed, then brief behavioral therapies are the treatment of choice, because they have shown long-lasting benefit without worsening of drinking outcomes. Medications work faster, but they generally work only as long as they are taken. Melatonin agonists; sedating antidepressants, anticonvulsants, and antipsychotics; and benzodiazepine receptor agonists each have their benefits and risks, which must be weighed and monitored to optimize outcomes. Some relapse prevention medications may also have sleep-promoting activity. Although it is assumed that treatment for insomnia will help prevent relapse, this has not been firmly established. Therefore, insomnia and alcohol dependence might be best thought of as co-occurring disorders, each of which requires its own treatment.
Our objectives were to characterise the microbiota in cystic fibrosis (CF) bronchoalveolar lavage fluid (BALF), and determine its relationship to inflammation and disease status.BALF from paediatric ...and adult CF patients and paediatric disease controls undergoing clinically indicated bronchoscopy was analysed for total bacterial load and for microbiota by 16S rDNA sequencing.We examined 191 BALF samples (146 CF and 45 disease controls) from 13 CF centres. In CF patients aged <2 years, nontraditional taxa (
,
and
) constituted ∼50% of the microbiota, whereas in CF patients aged ≥6 years, traditional CF taxa (
,
and
) predominated. Sequencing detected a dominant taxon not traditionally associated with CF (
or
) in 20% of CF BALF and identified bacteria in 24% of culture-negative BALF. Microbial diversity and relative abundance of
,
and
were inversely associated with airway inflammation. Microbiota communities were distinct in CF compared with disease controls, but did not differ based on pulmonary exacerbation status in CF.The CF microbiota detected in BALF differs with age. In CF patients aged <2 years,
predominates, whereas classic CF pathogens predominate in most older children and adults.
Clinical Practice Guideline: Sudden Hearing Loss (Update) Chandrasekhar, Sujana S; Tsai Do, Betty S; Schwartz, Seth R ...
Otolaryngology and head and neck surgery/Otolaryngology--head and neck surgery,
08/2019, Letnik:
161, Številka:
1_suppl
Journal Article
Recenzirano
Odprti dostop
Sudden hearing loss is a frightening symptom that often prompts an urgent or emergent visit to a health care provider. It is frequently but not universally accompanied by tinnitus and/or vertigo. ...Sudden sensorineural hearing loss affects 5 to 27 per 100,000 people annually, with about 66,000 new cases per year in the United States. This guideline update provides evidence-based recommendations for the diagnosis, management, and follow-up of patients who present with sudden hearing loss. It focuses on sudden sensorineural hearing loss in adult patients aged ≥18 years and primarily on those with idiopathic sudden sensorineural hearing loss. Prompt recognition and management of sudden sensorineural hearing loss may improve hearing recovery and patient quality of life. The guideline update is intended for all clinicians who diagnose or manage adult patients who present with sudden hearing loss.
The purpose of this guideline update is to provide clinicians with evidence-based recommendations in evaluating patients with sudden hearing loss and sudden sensorineural hearing loss, with particular emphasis on managing idiopathic sudden sensorineural hearing loss. The guideline update group recognized that patients enter the health care system with sudden hearing loss as a nonspecific primary complaint. Therefore, the initial recommendations of this guideline update address distinguishing sensorineural hearing loss from conductive hearing loss at the time of presentation with hearing loss. They also clarify the need to identify rare, nonidiopathic sudden sensorineural hearing loss to help separate those patients from those with idiopathic sudden sensorineural hearing loss, who are the target population for the therapeutic interventions that make up the bulk of the guideline update. By focusing on opportunities for quality improvement, this guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients.
Consistent with the American Academy of Otolaryngology-Head and Neck Surgery Foundation's "Clinical Practice Guideline Development Manual, Third Edition" (Rosenfeld et al.
. 2013;1481:S1-S55), the guideline update group was convened with representation from the disciplines of otolaryngology-head and neck surgery, otology, neurotology, family medicine, audiology, emergency medicine, neurology, radiology, advanced practice nursing, and consumer advocacy. A systematic review of the literature was performed, and the prior clinical practice guideline on sudden hearing loss was reviewed in detail. Key Action Statements (KASs) were updated with new literature, and evidence profiles were brought up to the current standard. Research needs identified in the original clinical practice guideline and data addressing them were reviewed. Current research needs were identified and delineated.
The guideline update group made
the following: (KAS 1) Clinicians should distinguish sensorineural hearing loss from conductive hearing loss when a patient first presents with sudden hearing loss. (KAS 7) Clinicians should educate patients with sudden sensorineural hearing loss about the natural history of the condition, the benefits and risks of medical interventions, and the limitations of existing evidence regarding efficacy. (KAS 13) Clinicians should counsel patients with sudden sensorineural hearing loss who have residual hearing loss and/or tinnitus about the possible benefits of audiologic rehabilitation and other supportive measures. These strong recommendations were modified from the initial clinical practice guideline for clarity and timing of intervention. The guideline update group made
following: (KAS 3) Clinicians should
order routine computed tomography of the head in the initial evaluation of a patient with presumptive sudden sensorineural hearing loss. (KAS 5) Clinicians should
obtain routine laboratory tests in patients with sudden sensorineural hearing loss. (KAS 11) Clinicians should
routinely prescribe antivirals, thrombolytics, vasodilators, or vasoactive substances to patients with sudden sensorineural hearing loss. The guideline update group made
the following: (KAS 2) Clinicians should assess patients with presumptive sudden sensorineural hearing loss through history and physical examination for bilateral sudden hearing loss, recurrent episodes of sudden hearing loss, and/or focal neurologic findings. (KAS 4) In patients with sudden hearing loss, clinicians should obtain, or refer to a clinician who can obtain, audiometry as soon as possible (within 14 days of symptom onset) to confirm the diagnosis of sudden sensorineural hearing loss. (KAS 6) Clinicians should evaluate patients with sudden sensorineural hearing loss for retrocochlear pathology by obtaining magnetic resonance imaging or auditory brainstem response. (KAS 10) Clinicians should offer, or refer to a clinician who can offer, intratympanic steroid therapy when patients have incomplete recovery from sudden sensorineural hearing loss 2 to 6 weeks after onset of symptoms. (KAS 12) Clinicians should obtain follow-up audiometric evaluation for patients with sudden sensorineural hearing loss at the conclusion of treatment and within 6 months of completion of treatment. These recommendations were clarified in terms of timing of intervention and audiometry and method of retrocochlear workup. The guideline update group offered the following KASs as
: (KAS 8) Clinicians may offer corticosteroids as initial therapy to patients with sudden sensorineural hearing loss within 2 weeks of symptom onset. (KAS 9a) Clinicians may offer, or refer to a clinician who can offer, hyperbaric oxygen therapy combined with steroid therapy within 2 weeks of onset of sudden sensorineural hearing loss. (KAS 9b) Clinicians may offer, or refer to a clinician who can offer, hyperbaric oxygen therapy combined with steroid therapy as salvage therapy within 1 month of onset of sudden sensorineural hearing loss.
Incorporation of new evidence profiles to include quality improvement opportunities, confidence in the evidence, and differences of opinion Included 10 clinical practice guidelines, 29 new systematic reviews, and 36 new randomized controlled trials Highlights the urgency of evaluation and initiation of treatment, if treatment is offered, by emphasizing the time from symptom occurrence Clarification of terminology by changing potentially unclear statements; use of the term
to mean idiopathic sudden sensorineural hearing loss to emphasize that >90% of sudden sensorineural hearing loss is idiopathic sudden sensorineural hearing loss and to avoid confusion in nomenclature for the reader Changes to the KASs from the original guideline: KAS 1-When a patient first presents with sudden hearing loss, conductive hearing loss should be distinguished from sensorineural. KAS 2-The utility of history and physical examination when assessing for modifying factors is emphasized. KAS 3-The word "routine" is added to clarify that this statement addresses nontargeted head computerized tomography scan that is often ordered in the emergency room setting for patients presenting with sudden hearing loss. It does not refer to targeted scans, such as temporal bone computerized tomography scan, to assess for temporal bone pathology. KAS 4-The importance of audiometric confirmation of hearing status as soon as possible and within 14 days of symptom onset is emphasized. KAS 5-New studies were added to confirm the lack of benefit of nontargeted laboratory testing in sudden sensorineural hearing loss. KAS 6-Audiometric follow-up is excluded as a reasonable workup for retrocochlear pathology. Magnetic resonance imaging, computerized tomography scan if magnetic resonance imaging cannot be done, and, secondarily, auditory brainstem response evaluation are the modalities recommended. A time frame for such testing is not specified, nor is it specified which clinician should be ordering this workup; however, it is implied that it would be the general or subspecialty otolaryngologist. KAS 7-The importance of shared decision making is highlighted, and salient points are emphasized. KAS 8-The option for corticosteroid intervention within 2 weeks of symptom onset is emphasized. KAS 9-Changed to KAS 9A and 9B. Hyperbaric oxygen therapy remains an option but only when combined with steroid therapy for either initial treatment (9A) or salvage therapy (9B). The timing of initial therapy is within 2 weeks of onset, and that of salvage therapy is within 1 month of onset of sudden sensorineural hearing loss. KAS 10-Intratympanic steroid therapy for salvage is recommended within 2 to 6 weeks following onset of sudden sensorineural hearing loss. The time to treatment is defined and emphasized. KAS 11-Antioxidants were removed from the list of interventions that the clinical practice guideline recommends against using. KAS 12-Follow-up audiometry at conclusion of treatment and also within 6 months posttreatment is added. KAS 13-This statement on audiologic rehabilitation includes patients who have residual hearing loss and/or tinnitus who may benefit from treatment. Addition of an algorithm outlining KASs Enhanced emphasis on patient education and shared decision making with tools provided to assist in same.
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