Novel Automated Self-adjusting Subcutaneous Insulin Algorithm Improves Glycemic Control and Physician Efficiency in Hospitalized Patients.

BACKGROUND: Hyperglycemia occurs in 22% to 46% of hospitalized patients, negatively affecting patient outcomes, including mortality, inpatient complications, length of stay, and hospital costs. Achieving inpatient glycemic control is challenging due to inconsistent caloric intake, changes from home medications, a catabolic state in the setting of acute illness, consequences of acute inflammation, intercurrent infection, and limitations in labor-intensive glucose monitoring and insulin administration. METHOD: We conducted a retrospective cross-sectional analysis at the University of California San Francisco hospitals between September 3, 2020 and September 2, 2021, comparing point-of-care glucose measurements in patients on nil per os (NPO), continuous total parenteral nutrition, or continuous tube feeding assigned to our novel automated self-adjusting subcutaneous insulin algorithm (SQIA) or conventional, physician-driven insulin dosing. We also evaluated physician efficiency by tracking the number of insulin orders placed or modified. RESULTS: The proportion of glucose in range (70-180 mg/dL) was higher in the SQIA group than in the conventional group (71.0% vs 69.0%, P = .153). The SQIA led to a lower proportion of severe hyperglycemia (>250 mg/dL; 5.8% vs 7.2%, P = .017), hypoglycemia (54-69 mg/dL; 0.8% vs 1.2%, P = .029), and severe hypoglycemia (<54 mg/dL; 0.3% vs 0.5%, P = .076) events. The number of orders a physician had to place while a patient was on the SQIA was reduced by a factor of more than 12, when compared with while a patient was on conventional insulin dosing. CONCLUSIONS: The SQIA reduced severe hyperglycemia, hypoglycemia, and severe hypoglycemia compared with conventional insulin dosing. It also improved physician efficiency by reducing the number of order modifications a physician had to place.

The Night and Day Challenge of Sleep Disorders and Insomnia: A Narrative Review.

This is a narrative review of sleep disorders, especially chronic insomnia, as a primary diagnosis or as a comorbid diagnosis associated with different psychiatric and organic diseases. The epidemiological evidence is reviewed, the diagnostic criteria most frequently used in clinical practice are examined, and a series of therapeutic recommendations for the correct treatment of this pathology is presented. Sleep disorders are very prevalent in the general population (one-third experiences difficulty with sleep initiation/maintenance at least once a week, and about 6-15% meet the criteria for insomnia disorders), but remain relatively poorly understood and frequently overlooked by healthcare professionals. Prevalence estimates of insomnia disorder vary between 5% and 20%. Sleep disorders co-exist with psychiatric and medical conditions with an interactive and bidirectional relationship. About 70-80% of psychiatric patients show some sleep disturbance and there is a correlation between the severity of the sleep disturbance and the severity of the psychopathology. Untreated sleep disorders increase the risk of cardiovascular events, cognitive impairment, motor vehicle accidents, obesity, diabetes, and efficiency and safety at work, leading to increased all-cause healthcare utilization and being a strong predictor of sick leave or disability pension and poor quality of life. Sleep disorders can cause drowsiness or excessive daytime sleepiness, which can lead to functional impairment in 15% of the general adult population. Sleep quality should be a routine target in the evaluation of patients with psychiatric and non-psychiatric diseases to ensure sleep health based on early diagnosis and adequate therapeutic approaches.

Alternative Approaches for Addressing Acute Agitation in Schizophrenia and Bipolar Disorder.

Importance: The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease the risk of escalation to aggression and the potential for serious harm to the patient, health care providers, and others.Observations: A commonly used approach for the management of acute agitation has been the intramuscular administration of antipsychotic medications and/or benzodiazepines. However, US Food and Drug Administration-approved treatments with alternative routes of delivery now include inhaled loxapine powder and, more recently, dexmedetomidine sublingual film. Two formulations of intranasal olanzapine for acute agitation are in development.Conclusions and Relevance: Intranasal formulations offer the potential for favorable pharmacokinetics and onset of action combined with ease of delivery obviating the need for injections and are thus consistent with patient-centered factors such as preference and self-administration. In this review, alternative methods of medication delivery are discussed, with an emphasis on the potential for intranasal administration to treat acute agitation in adult patients with schizophrenia or bipolar disorder.Prim Care Companion CNS Disord 2024;26(1):23nr03596. Author affiliations are listed at the end of this article.

Formulating a national position statement and guide on modern theranostics in the Philippines.

Barriers to the establishment of advanced technologies in developing countries were overcome when modern theranostics pertaining to the use of Ga-68 and Lu-177 PSMA and DOTATATE were first offered to patients in the Philippines in early 2018. However, significant growth was not experienced at St. Luke's Medical Center for five years and lutetium was not yet distributed to other institutions by a radiopharmaceutical supplier. Due to the relative novelty and rapid expansion of theranostics worldwide, position statements were released by the Australasian Association of Nuclear Medicine Specialists, European Association of Nuclear Medicine, Society of Nuclear Medicine and Molecular Imaging, and International Atomic Energy Agency primarily to uphold patient safety and ensure a level of standard among its practitioners. Subsequently in the latter half of 2022, these were adopted and modified according to what is feasible and applicable locally within the Philippine Society of Nuclear Medicine, considering the current status and future possibilities. Different representatives were involved, and several groups were mobilized for successful implementation. A liability clause was incorporated to discourage unprofessional acts.

The Night and Day Challenge of Sleep Disorders and Insomnia: A Narrative Review

This is a narrative review of sleep disorders, especially chronic insomnia, as a primary diagnosis or as a comorbid diagnosis associated with different psychiatric and organic diseases. The epidemiological evidence is reviewed, the diagnostic criteria most frequently used in clinical practice are examined, and a series of therapeutic recommendations for the correct treatment of this pathology is presented. Sleep disorders are very prevalent in the general population (one-third experiences difficulty with sleep initiation/maintenance at least once a week, and about 6–15% meet the criteria for insomnia disorders), but remain relatively poorly understood and frequently overlooked by healthcare professionals. Prevalence estimates of insomnia disorder vary between 5% and 20%. Sleep disorders co-exist with psychiatric and medical conditions with an interactive and bidirectional relationship. About 70–80% of psychiatric patients show some sleep disturbance and there is a correlation between the severity of the sleep disturbance and the severity of the psychopathology. Untreated sleep disorders increase the risk of cardiovascular events, cognitive impairment, motor vehicle accidents, obesity, diabetes, and efficiency and safety at work, leading to increased all-cause healthcare utilization and being a strong predictor of sick leave or disability pension and poor quality of life. Sleep disorders can cause drowsiness or excessive daytime sleepiness, which can lead to functional impairment in 15% of the general adult population. Sleep quality should be a routine target in the evaluation of patients with psychiatric and non-psychiatric diseases to ensure sleep health based on early diagnosis and adequate therapeutic approaches. (AU)

Engram cell connectivity as a mechanism for information encoding and memory function.

Information derived from experiences is incorporated into the brain as changes to ensembles of cells, termed engram cells, which allow memory storage and recall. The mechanism by which those changes hold specific information is unclear. Here, we test the hypothesis that the specific synaptic wiring between engram cells is the substrate of information storage. First, we monitor how learning modifies the connectivity pattern between engram cells at a monosynaptic connection involving the hippocampal ventral CA1 (vCA1) region and the amygdala. Then, we assess the functional significance of these connectivity changes by artificially activating or inhibiting its presynaptic and postsynaptic components, respectively. Finally, we identify a synaptic plasticity mechanism mediated by postsynaptic density protein 95 (PSD-95), which impacts the connectivity pattern among engram cells and contributes to the long-term stability of the memory. These findings impact our theory of learning and memory by helping us explain the translation of specific information into engram cells and how these connections shape brain function.

Immune activation state modulates infant engram expression across development.

Infantile amnesia is possibly the most ubiquitous form of memory loss in mammals. We investigated how memories are stored in the brain throughout development by integrating engram labeling technology with mouse models of infantile amnesia. Here, we found a phenomenon in which male offspring in maternal immune activation models of autism spectrum disorder do not experience infantile amnesia. Maternal immune activation altered engram ensemble size and dendritic spine plasticity. We rescued the same apparently forgotten infantile memories in neurotypical mice by optogenetically reactivating dentate gyrus engram cells labeled during complex experiences in infancy. Furthermore, we permanently reinstated lost infantile memories by artificially updating the memory engram, demonstrating that infantile amnesia is a reversible process. Our findings suggest not only that infantile amnesia is due to a reversible retrieval deficit in engram expression but also that immune activation during development modulates innate, and reversible, forgetting switches that determine whether infantile amnesia will occur.

Meta-analysis of the effects of adjuvant drugs in co-occurring bipolar and substance use disorder.

BACKGROUND: Individuals with bipolar disorder (BD) often have co-occurring substance use disorders (SUDs), which substantially impoverish the course of illness. Despite the importance of this dual diagnosis, the evidence of the efficacy and safety of adjuvant treatments is mostly unknown. OBJECTIVE: To perform a meta-analysis to evaluate the efficacy and safety of adjuvant drugs in patients with co-occurring BD and SUD. METHODS: We searched PubMed, Scopus, and Web of Knowledge until 30th April 2022 for randomized clinical trials (RCT) evaluating the efficacy and safety of adjuvant drugs compared to placebo in patients with a dual diagnosis of BD and SUD. We meta-analyzed the effect of adjuvant drugs on general outcomes (illness severity, mania, depression, anxiety, abstinence, substance craving, substance use, gamma-GT, adherence, and adverse events) and used the results to objectively assess the quality of the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. For completeness, we also report the specific effects of specific adjuvant drugs in patients with specific substance disorders. RESULTS: We included 15 RCT studies (9 alcohol, 3 cocaine, 2 nicotine, and 1 cannabis) comprising 628 patients allocated to treatment and 622 to placebo. There was low-quality evidence that adjuvant drugs may reduce illness severity (g=-0.25, 95% CI: -0.44, -0.06), and very-low quality evidence that they may decrease substance use (g=-0.23, 95% CI: -0.44, -0.02) and increase substance abstinence (g=0.21, 95% CI: 0.04, 0.38). DISCUSSION: There is low-quality evidence that adjuvant drugs may help reduce illness severity, probably via facilitating abstinence and lower substance use. However, the evidence is weak; thus, these results should be considered cautiously until better evidence exists.

Adaptive expression of engrams by retroactive interference.

Long-term memories are stored as configurations of neuronal ensembles, termed engrams. Although investigation of engram cell properties and functionality in memory recall has been extensive, less is known about how engram cells are affected by forgetting. We describe a form of interference-based forgetting using an object memory behavioral paradigm. By using activity-dependent cell labeling, we show that although retroactive interference results in decreased engram cell reactivation during recall trials, optogenetic stimulation of the labeled engram cells is sufficient to induce memory retrieval. Forgotten engrams may be reinstated via the presentation of similar or related environmental information. Furthermore, we demonstrate that engram activity is necessary for interference to occur. Taken together, these findings indicate that retroactive interference modules engram expression in a manner that is both reversible and updatable. Inference may constitute a form of adaptive forgetting where, in everyday life, new perceptual and environmental inputs modulate the natural forgetting process.

Factors Contributing to Stroke Clinic Follow-Up "No Show": A Quality Improvement Project.

Objective Controlling modifiable risk factors provides a strong impact on secondary stroke prevention. Stroke outpatient follow-up (OPFU) provides a significant role in assuring these goals are met. However, in our institute in 2018, one out of four patients was not seen in the stroke clinic after their stroke. To increase this ratio, we instituted a performance improvement project (PIP) to determine factors that contribute to OPFU and offered rescheduling after their missed appointment. Methods The nurse scheduler called patients labeled as "no-show," asked for reasons for the missed appointment, and offered rescheduling accordingly. Other data were collected retrospectively. Results Of the 53 "no show" patients, most were females, single, Black, uninsured, and had a Modified Rankin Scale (MRS) of 0. Of the 30 patients who participated in the phone interview, a most common reason for "no show" was transportation. Fifteen out of 27 patients kept their rescheduled appointment, increasing patients seen in the clinic by 6.7%. Conclusion This PIP determined contributing factors on health care seeking practices of our stroke clinic patients allowing necessary improvements in our institute. Rescheduling increased the number of stroke patients seen in the stroke clinic. Our general neurology ambulatory department consequently adopted this process as well.

The Enigma of Autoimmunity: A Case of Subacute Sclerosing Panencephalitis in a Patient Diagnosed With Systemic Lupus Erythematosus.

Subacute sclerosing panencephalitis (SSPE) is a rare complication of measles characterized by progressive neurological deterioration. The onset usually occurs about seven to 10 years after the measles infection. Aside from an earlier age of measles infection, factors that may influence the susceptibility for its development is unknown. There is a paucity of data regarding the course of SSPE in the presence of concomitant autoimmune conditions such as systemic lupus erythematosus (SLE). We report a case of a 19-year-old female who presented with new onset recurrent generalized tonic-clonic seizures, malar rash, and cutaneous erythematous, maculopapular eruptions. Antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA) serologic examination yielded positive results favoring the diagnosis of SLE. Further in the course of illness, the patient developed generalized myoclonic jerks and progressive decline in language, cognitive, and motor functions. Subsequent investigation showed an elevated anti-measles antibody titer in the cerebrospinal fluid, and periodic generalized, bilaterally synchronous, and symmetric high voltage slow-wave complexes in the EEG. These findings and the typical evolution of neurologic manifestations fulfilled two major and one minor Dyken's criteria for the diagnosis of SSPE. It is postulated that some autoimmune-mediated responses may contribute to the evolution of SSPE. Autoimmune complexes in SLE induce downregulation of T-cell responses which accelerate the loss of antibodies formed against other diseases such as the measles virus that may lead to increased susceptibility to infection. SSPE is hypothesized to result from the downregulation of host-immune responses which leads to incomplete measles viral clearance. To the best of the authors' knowledge, this is the first published case of SSPE with active SLE.

Proteasome inhibitor bortezomib stabilizes and activates p53 in hematopoietic stem/progenitors and double-negative T cells in vivo.

We have previously shown that proteasome inhibitor bortezomib stabilizes p53 in stem and progenitor cells within gastrointestinal tissues. Here, we characterize the effect of bortezomib treatment on primary and secondary lymphoid tissues in mice. We find that bortezomib stabilizes p53 in significant fractions of hematopoietic stem and progenitor cells in the bone marrow, including common lymphoid and myeloid progenitors, granulocyte-monocyte progenitors, and dendritic cell progenitors. The stabilization of p53 is also observed in multipotent progenitors and hematopoietic stem cells, albeit at lower frequencies. In the thymus, bortezomib stabilizes p53 in CD4-CD8- T cells. Although there is less p53 stabilization in secondary lymphoid organs, cells in the germinal center of the spleen and Peyer's patch accumulate p53 in response to bortezomib. Bortezomib induces the upregulation of p53 target genes and p53 dependent/independent apoptosis in the bone marrow and thymus, suggesting that cells in these organs are robustly affected by proteasome inhibition. Comparative analysis of cell percentages in the bone marrow indicates expanded stem and multipotent progenitor pools in p53R172H mutant mice compared with p53 wild-type mice, suggesting a critical role for p53 in regulating the development and maturation of hematopoietic cells in the bone marrow. We propose that progenitors along the hematopoietic differentiation pathway express relatively high levels of p53 protein, which under steady-state conditions is constantly degraded by Mdm2 E3 ligase; however, these cells rapidly respond to stress to regulate stem cell renewal and consequently maintain the genomic integrity of hematopoietic stem/progenitor cell populations.

Polymer-based particles against pathogenic fungi: A non-uptake delivery of compounds.

The therapy of life-threatening fungal infections is limited and needs urgent improvement. This is in part due to toxic side effects of clinically used antifungal compounds or their limited delivery to fungal structures. Until today, it is a matter of debate how drugs or drug-delivery systems can efficiently reach the intracellular lumen of fungal cells and how this can be improved. Here, we addressed both questions by applying two different polymeric particles for delivery of compounds. Their formulation was based on two biocompatible polymers, i.e., poly(lactic-co-glycolic acid)50:50 and poly(methyl methacrylate-stat-methacrylic acid)90:10 yielding particles with hydrodynamic diameters ranging from 100 to 300 nm. The polymers were covalently labeled with the fluorescent dye DY-550 to monitor the interaction between particles and fungi by confocal laser scanning microscopy. Furthermore, the fluorescent dye coumarin-6 and the antifungal drug itraconazole were successfully encapsulated in particles to study the fate of both the cargo and the particle when interacting with the clinically most important human-pathogenic fungi Aspergillus fumigatus, A. terreus, Candida albicans, and Cryptococcus neoformans. While the polymers were exclusively located on the fungal surface, the encapsulated cargo was efficiently transported into fungal hyphae, indicated by increased intracellular fluorescence signals due to coumarin-6. In accordance with this finding, compared to the pristine drug a reduced minimal inhibitory concentration for itraconazole was determined, when it was encapsulated. Together, the herein used polymeric particles were not internalized by pathogenic fungi but were able to efficiently deliver hydrophobic cargos into fungal cells.

From harassment to disappearance: Young women's feelings of insecurity in public spaces.

BACKGROUND: There are processes of gender socialization that increase the vulnerability of young women against a continuum of threats in the public space. This study explored the feeling of insecurity in public spaces among young women in a city located near the northern border of Mexico. METHODS AND FINDINGS: This study was based on the tradition of grounded theory. Purposive sampling was used, and 24 group interviews were conducted with junior high school, high school and university students to understand the conditions that favour the emergence of the feeling of insecurity, its psychosocial consequences and management strategies. A computer-assisted qualitative analysis was performed using MAXQDA 18 software. The study showed that street harassment was manifested mainly as sexual harassment but generated a continuous threat of feminicide and disappearance. Young women experienced discomfort and restrictions on mobility, and they had to assume individual responsibility for their safety in the absence of support from the state. CONCLUSIONS: The interaction between gender and age determines the vulnerability to crime in urban spaces. Future studies could analyse the chronic impact of this continuum of threats and develop psychosocial interventions that promote the empowerment of young women.

Predictors of Early Mortality for Mechanically Ventilated Spontaneous Intracerebral Hemorrhage Patients.

Introduction Spontaneous intracerebral hemorrhage (sICH) carries a high mortality burden. Limited data are available on early mortality (EM) and sICH. This study attempted to identify the independent predictors of EM and analyze the mortality characteristics for mechanically ventilated patients with sICHs at a tertiary care hospital over a period of five years. Methods An Institutional Review Board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPPA)-compliant retrospective analysis was performed on sICH patients admitted at the University of Mississippi Medical Center Neuroscience Intensive Care Unit between January 1, 2013, to December 31, 2017. Patients were divided into two cohorts: EM cohort (death within seven days of admission) versus survivor cohort (alive more than seven days after admission). Demographic, comorbidity, clinical, and radiographic data were collected for each patient. Outcomes were compared utilizing student t-test or Mann-Whitney U tests for continuous variables. Logistic regression analysis was performed to determine independent predictors of EM. Results A total of 204 mechanically ventilated patients with sICHs, with a mean age of 59.73 (SD ±14.30), mostly African American (137, 67%), were included in the study. The characteristics of the two cohorts were comparable except the EM cohort had a lower proportion of patients with hypertension and end-stage renal disease; lower median Glasgow Coma Score (GCS) on admission; lower proportion of surgical evacuation and external ventricular drain (EVD) placement; higher proportion of lobar hemorrhage, brainstem involvement, midline shift, hydrocephalus, intraventricular hemorrhage component, and right-sided intracerebral hemorrhage (ICH); higher median ICH score; and higher ICH volume compared to the survivor cohort. Overall, the mortality of mechanically ventilated sICH patients in this institution was 53% (N=109), with 47% (N=96) not surviving beyond seven days. Logistic regression analysis revealed that ICH volume and brainstem involvement increased the odds of EM, while a history of hypertension, surgical evacuation, and EVD placement decreased the odds of EM. Conclusions This study on mechanically ventilated sICH patients identified ICH volume and brainstem involvement as independent predictors of increased EM. History of hypertension, EVD placement, and surgical evacuation decreased its odds. Further studies should be conducted to explore potentially modifiable processes that can improve patient outcomes, most importantly EM, especially in this cohort of patients.

A Novel Dynamin 2 Mutation Causing Dominant Intermediate Charcot-Marie-Tooth Neuropathy: Case Report.

Dynamin 2 mutations are associated with Charcot-Marie-Tooth neuropathy. We report two siblings with a novel missense heterozygous point mutation (c.1609 G>A) in the highly conserved pleckstrin homology domain in exon 15 of Dynamin 2 presenting with progressive length-dependent sensorimotor polyneuropathy with mixed demyelinating and axonal features on electrodiagnostic studies. The previously unrecognized missense point mutation, which was inherited from their symptomatic but previously undiagnosed mother, was determined to be likely pathogenic based on a non-conservative amino acid substitution (p.Gly537Ser) that is predicted to damage secondary protein structure or function. This report emphasizes the importance of recognizing inherited neuropathies in clinical practice and evaluating suspected pathogenic gene variants initially classified to be of undetermined clinical significance in family cohorts. These cases add to the spectrum of pathogenic Dynamin 2 mutations associated with dominant-intermediate Charcot-Marie-Tooth neuropathy.

Baleen whale inhalation variability revealed using animal-borne video tags.

Empirical metabolic rate and oxygen consumption estimates for free-ranging whales have been limited to counting respiratory events at the surface. Because these observations were limited and generally viewed from afar, variability in respiratory properties was unknown and oxygen consumption estimates assumed constant breath-to-breath tidal volume and oxygen uptake. However, evidence suggests that cetaceans in human care vary tidal volume and breathing frequency to meet aerobic demand, which would significantly impact energetic estimates if the findings held in free-ranging species. In this study, we used suction cup-attached video tags positioned posterior to the nares of two humpback whales (Megaptera novaeangliae) and four Antarctic minke whales (Balaenoptera bonaerensis) to measure inhalation duration, relative nares expansion, and maximum nares expansion. Inhalation duration and nares expansion varied between and within initial, middle, and terminal breaths of surface sequences between dives. The initial and middle breaths exhibited the least variability and had the shortest durations and smallest nares expansions. In contrast, terminal breaths were highly variable, with the longest inhalation durations and the largest nares expansions. Our results demonstrate breath-to-breath variability in duration and nares expansion, suggesting differential oxygen exchange in each breath during the surface interval. With future validation, inhalation duration or nares area could be used alongside respiratory frequency to improve oxygen consumption estimates by accounting for breath-to-breath variation in wild whales.