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Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.
We develop a model that relates self-control to cooperation patterns in social dilemmas, and we test the model in a laboratory public goods experiment. As predicted, we find a robust association between stronger self-control and higher levels of cooperation, and the association is at its strongest when the decision maker’s risk aversion is low and the cooperation levels of others high. We interpret the pattern as evidence for the notion that individuals may experience an impulse to act in self-interest—and that cooperative behavior benefits from self-control. Free-riders differ from other contributor types only in their tendency not to have identified a self-control conflict in the first place.
Increasing daylight exposure might be a simple way to improve mental health. However, little is known about daylight-symptom associations in depressive disorders.
Methods
In a subset of the Australian Genetics of Depression Study (N = 13,480; 75% female), we explored associations between self-reported number of hours spent in daylight on a typical workday and free day and seven symptom dimensions: depressive (overall, somatic, psychological); hypo-manic-like; psychotic-like; insomnia; and daytime sleepiness. Polygenic scores for major depressive disorder (MDD); bipolar disorder (BD); and schizophrenia (SCZ) were calculated. Models were adjusted for age, sex, shift work status, employment status, season, and educational attainment. Exploratory analyses examined age-stratified associations (18–24 years; 25–34 years; 35–64 years; 65 and older). Bonferroni-corrected associations (p < 0.004) are discussed.
Results
Adults with depression reported spending a median of one hour in daylight on workdays and three hours on free days. More daylight exposure on workdays and free days was associated with lower depressive (overall, psychological, somatic) and insomnia symptoms (p’s<0.001), but higher hypo-manic-like symptoms (p’s<0.002). Genetic loading for MDD and SCZ were associated with less daylight exposure in unadjusted correlational analyses (effect sizes were not meaningful). Exploratory analyses revealed age-related heterogeneity. Among 18–24-year-olds, no symptom dimensions were associated with daylight. By contrast, for the older age groups, there was a pattern of more daylight exposure and lower insomnia symptoms (p < 0.003) (except for 25–34-year-olds on free days, p = 0.019); and lower depressive symptoms with more daylight on free days, and to some extent workdays (depending on the age-group).
Conclusions
Exploration of the causal status of daylight in depression is warranted.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Childhood sexual abuse (CSA) and emotional maltreatment are salient risk factors for the development of major depressive disorder (MDD) in women. However, the type- and timing-specific effects of emotional maltreatment experienced during adolescence on future depressive symptomatology in women with CSA have not been explored. The goal of this study was to fill this gap.
Methods
In total, 203 women (ages 20–32) with current depressive symptoms and CSA (MDD/CSA), remitted depressive symptoms and CSA (rMDD/CSA), and current depressive symptoms without CSA (MDD/no CSA) were recruited from the community and completed self-report measures. Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II) and a detailed maltreatment history was collected using the Maltreatment and Abuse Chronology of Exposure (MACE). Differences in maltreatment exposure characteristics, including multiplicity and severity of maltreatment, as well as the chronologies of emotional maltreatment subtypes were compared among groups. A random forest machine-learning algorithm was utilized to assess the impact of exposure to emotional maltreatment subtypes at specific ages on current depressive symptoms.
Results
MDD/CSA women reported greater prevalence and severity of emotional maltreatment relative to rMDD/CSA and MDD/no CSA women [F(2,196) = 9.33, p < 0.001], specifically from ages 12 to 18. The strongest predictor of current depressive symptoms was parental verbal abuse at age 18 for both MDD/CSA women (variable importance [VI] = 1.08, p = 0.006) and MDD/no CSA women (VI = 0.68, p = 0.004).
Conclusions
Targeting emotional maltreatment during late adolescence might prove beneficial for future intervention efforts for MDD following CSA.
Objectives: To evaluate the effect and safety of Cannabidiol (CBD) on behavioral and psychological symptoms in elderly with Vascular dementia (VD).
Methods: Double- blind, randomized, placebo-controlled clinical trial involving elderly patients with VD at the psychogeriatrics and vascular dementia outpatient clinic at Hospital das Clínicas de Ribeirão Preto. The intervention evaluated was the use of CBD 300mg/day compared to placebo. The instruments used are: Neuropsychiatric Inventory, Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Scale, Side Effects Scale, Mini- Mental State Examination, Brief Cognitive Screening Battery, Katz Index of Independence in Activities of Daily Living, Lawton Instrumental Activities of Daily Living Scale, Informant Questionnaire on Cognitive Decline in the Elderly, Zarit Burden Inventory. The included participants were assessed at the beginning of the study (baseline assessment), in the first, second and fourth weeks after the start of the clinicaltrial.
Results: 30 participants were included. The mixed ANOVA with repeated measures showed that there is an effect of the interaction time and group (F (2.12; 59.43) = 4.02; p < 0.05; ηp2 = 0.13) on the total score of the brief scale psychiatric assessment and neuropsychiatric inventory (F (1.58; 44.31) = 3.61; p =0.05; ηp2 = 0.11). The mixed ANOVA of repeated measures showed no effect of the interaction of time and group for the mini-mental state examination, brief cognitive screening battery. Adverse effects were mild and transient, and similar to the placebo group.
Conclusions: In this study, cannabidiol reduced psychological and behavioral symptoms in patients with vascular dementia. Future studies with larger samples are needed to confirm the findings. (F(1.58;44.31) = 3.61; p =0.05; ηp2 = 0.11). The mixed ANOVA of repeated measures showed no effect of the interaction of time and group for the mini-mental state examination, brief cognitive screening battery. Adverse effects were mild and transient, and similar to the placebo group.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.
Methods:
A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey.
Results:
All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey).
Conclusion:
Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
Tourette’s syndrome (TS) is a disorder characterized by repetitive, involuntary movements, and vocalizations known as tics. While there are existing treatment options, there is a growing need for novel pharmacological approaches to manage the symptoms of TS effectively. This study delves into the emerging field of using cannabinoids as a potential treatment for Tourette’s syndrome.
Objectives
The primary objectives of this review are to examine the current evidence base for the use of cannabinoids in the treatment of Tourette’s syndrome, to assess the biological rationale supporting the use of cannabinoids in managing tic severity, to provide insights into the results of existing clinical trials involving cannabinoids and Tourette’s syndrome, and to draw conclusions regarding the potential efficacy and safety of cannabinoid-based treatments for TS.
Methods
Narrative review of the available scientific literature.
Results
There is a strong biological rationale for how cannabinoids could impact tic severity. The endocannabinoid system plays a crucial role in regulating various physiological processes, including motor control and neurotransmitter release. Activation of cannabinoid receptors in the brain may modulate these processes, potentially reducing tics. While limited, two small randomized, placebo-controlled trials of THC have been conducted in TS patients. These trials suggested potential benefits of cannabis-derived agents in reducing tic frequency and severity. Self-report and examiner rating scales demonstrated significant improvements in tic symptoms. The trials indicated that THC treatment did not result in significant adverse effects in TS patients.
Conclusions
The exploration of cannabinoids as a treatment option for Tourette’s syndrome is promising but requires further investigation. The biological mechanisms through which cannabinoids may affect tic severity in TS are sound, suggesting their potential as a therapeutic option. Existing trials with THC have shown encouraging results, demonstrating a reduction in tics without significant adverse effects. However, the limited number of trials warrants caution in drawing definitive conclusions. Despite the promising findings, the overall efficacy and safety of cannabinoid-based treatments remain largely unknown. Further trials are essential to address dosing, active ingredients, optimal administration, and potential long-term effects. Clinical use should be approached with caution. While early evidence is encouraging, additional rigorous studies are needed to establish the safety and efficacy of cannabinoid-based treatments for this disorder.
Obsessive-compulsive disorder (OCD) has a high prevalence and causes a significative reduction in functionality and quality of life.
First and second line treatment is ineffective in a variable percentage of patients. In such cases transcranial magnetic stimulation (TMS) may be considered.
Objectives
The goal of this study is to evaluate the impact of TMS treatment on obsessive-compulsive, anxious and depressive symptomatology in patients with OCD.
Methods
A prospective observational study was conducted, including all patients diagnosed with OCD who underwent TMS in the Psychiatry department of Centro Hospitalar Universitário de São João since March 2023.
Symptomatology was assessed using the Yale Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D) before and after treatment.
Statistical analysis was performed using the SPSS-Statistics program. A significance level of 0.05 was considered.
Results
As of October 31, 2023, nine individuals with OCD completed treatment with TMS, 33% male and with a median age of 40 years (range 33-57).
The median Y-BOCS score pre-TMS was 30 (range 20-33) and post-TMS 28 (range 16-34). The median difference was 2.5 (range -5-14) and was not statistically significant (p=0.128).
The median score on the HAM-A pre-TMS was 21 (range 9-41) and post-TMS 18 (range 11-24). The median difference was 0 points (range -4-21) and was not statistically significant (p=0.345).
The median HAM-D score pre-TMS was 26 (range 14-40) and post-TMS 19 (range 10-32). The median difference was 2.5 (range -3-20) and was not statistically significant (p=0.225).
Conclusions
Preliminary findings suggest that the impact of TMS on obsessive-compulsive, anxious, and depressive symptomatology in patients with OCD does not appear to be clinically or statistically significant.
Further results are necessary to confirm this trend.
Irvin D. Yalom defines existential psychotherapy as a dynamic therapeutic approach that focuses on concerns rooted in existence with the four ultimate concerns being death, isolation, meaning in life, and freedom. Patients in advanced stages of cancer often experience elevated levels of psychological distress, encompassing conditions such as depression, anxiety, and a sense of spiritual hopelessness. Recently, interest in spiritual well-being has prompted a new wave of interventions that directly target this population, namely logotherapy and other existential interventions based on existential principles.
Objectives
In this review, the primary focus was to comprehend the current evidence on the application of existential psychotherapy for individuals coping with advanced cancer and give an overview of the therapy approaches used.
Methods
Narrative review of scientific literature using Pubmed search engine.
Results
Terao and Satoh identified nine types of existential psychotherapies which were investigated using randomized controlled trials for patients with advanced cancer or in terminal care: Meaning-Centered Group Psychotherapy (MCGP), Individual Meaning-Centered Psychotherapy (IMCP), Meaning-Making intervention (MMi), Meaning of Life Intervention, Managing Cancer and Living Meaningfully (CALM), Hope Intervention, Cognitive and Existential Intervention, Dignity Therapy, and Life-Review Interviews. All deal with the issues pointed by Yalom. Existential or spiritual well-being improvements were validated in MCGP, IMCP, Meaning of Life intervention, and Life-Review intervention.
Conclusions
Current evidence is still based on a very limited number of studies. Additional research is needed to delve into the impact of existential psychotherapy on individuals facing advanced cancer.
In the review of recent literature, we found very few presentations of case reports in which the presumed association between psychiatric disorders and arachnoid cysts is discussed. Arachnoid cysts are rare brain tumors with little apparent symptomatic impact and in most cases, they are diagnosed incidentally. We present the case of a 15-year-old adolescent with a personal history of a previous severe depressive episode, as well as suspicion of serious mental pathology in the family. It presents a subacute onset episode, in the context of regular cannabis consumption, consisting of intense emotional lability and psychomotor restlessness, a tendency toward irritability, decreased sleep needs, and the appearance of delusional ideas of harm and self-referential interruption. During the study of the case, and incidentally, the cranial magnetic resonance imaging revealed the presence of an arachnoid cyst located in the left frontotemporal location, approximately 4 cm in diameter.
Objectives
(1) To describe the clinical particularities of this case, focusing on the diagnostic difficulties we faced. (2) To review current scientific evidence regarding the possible association between neuropsychiatric symptoms and arachnoid cysts.
Methods
A review of the patient’s clinical history was carried out and complementary tests were performed. Likewise, a review of the available scientific literature was also performed in relation to the appearance of neuropsychiatric symptoms associated with the presence of arachnoid cysts.
Results
The literature regarding the possible association between psychosis and arachnoid cysts is scarce. However, it is proposed that arachnoid cysts may be associated with various neuropsychiatric alterations, such as affective alterations, schizophrenia-like psychosis or amnestic symptoms. The atypicality in the symptoms sometimes leads us to suspect an organic origin of the condition, with some features such as associated memory deficits, emotional incontinence, movement disorders or neurological focal data; some of which are present in the case at hand.
Conclusions
There is controversy among different sources regarding the role of the cyst in the development of symptoms or, on the contrary, its presentation only as a chance finding. Further investigation focusing on clinical observations and neuroimaging is needed.
Men and women with psychosis have different courses and presentations of symptoms. Men with psychosis have an earlier onset of illness, more negative symptoms, and worse premorbid functioning. Women, on the other hand, have better social functioning and less substance abuse. Despite these evident differences, there are few studies that delve into these distinctions, especially from a subjective perspective.
Objectives
The aim of this study is to understand the differences in the perception of psychosis between men and women.
Methods
Five women and five men diagnosed with schizophrenia participated in the study. They were matched so that the age difference between them was no more than 5 years, with ages ranging from 40 to 56 years. Participants had not experienced acute decompensation of their underlying illness and had not required admission to an Acute Care Unit in the 6 months prior to inclusion in the study. Data collection was conducted through the Spanish translation of the Indiana Psychiatric Illness Interview, consisting of five parts: a narrative about their life, a narrative about the illness, questions related to how the illness has changed their life and what has not changed, the overall influence of the illness on their life, and lastly, expectations for the future.
Results
Men expressed more concerns about work (4 men versus 2 women), while women expressed more concerns about not having become mothers (3 out of 5 women, compared to one man). All participants shared experiences of isolation in intimate relationships, including romantic relationships. Regarding stigma, three women believed that people treated them like children and dismissed their opinions. However, two of them viewed this behavior from their loved ones positively. Two women discussed the impact that psychosis and medications had on their bodies and how others had reacted to these changes
Conclusions
The concerns and stigma associated with mental illness differ between genders. These differences should be taken into account when developing specific biopsychosocial treatment plans.
A variety of peer support workers have been integrated in the mental health workforce in several countries. The effectiveness of this approach is still inconclusive. However, some data reveals promising results. Some projects have integrated peer support intervention in the treatment of psychosis. In fact, UK clinical guidelines for psychosis advise the inclusion of peer support within Early Intervention in Psychosis services.
Objectives
The current study aims to evaluate how peer support may assist the intervention in psychosis and highlight challenges ahead in this field.
Methods
Narrative review of the available scientific literature.
Results
Research suggests that consistent and frequent peer support enhances social support and boosts self-confidence and the overall quality of life for people going through psychosis. Individuals diagnosed with severe mental illnesses who receive peer support reportedly experience an increased sense of control, hopefulness, and empowerment, enabling them to initiate positive changes in their lives. People going through psychosis experience internalized stigma. Destigmatization of psychotic experiences is a central theme of intervention in psychosis. Participants viewed peer support as a valuable form of assistance that could offer advantages to both peers (service users) and peer support workers.
Conclusions
Peer support makes a strong contribution to destigmatising psychosis. The available date is promising and supports the effectiveness of peer support in such instances. As projects of peer support in psychosis continue to be implemented, further research should provide additional insight into the effectiveness and inherent challenges of this type of intervention.
Psychotherapy serves as the foundation of care for individuals with borderline personality disorder (BPD), with pharmacotherapy being regarded as a supplementary measure to be considered when necessary. In clinical practice, however, most of BPD patients receive medication.
A major problem in the treatment of BPD is the lack of compliance derived from the pathological impulsivity of BPD patients. The use of long-acting antipsychotics (LAI) may be an option.
Objectives
This work aims to address the use of long-acting injectables in borderline personality disorder.
Methods
Non-systematic review of literature using the PubMed ® database, based on terms “Borderline Personality Disorder” and “Long-acting antipsychotics”. Only six articles were found.
Results
Several studies have shown promising results in the treatment of Borderline Personality Disorder (BPD) with long-acting injectable (LAI) antipsychotics. A six-month study using IM risperidone demonstrated significant improvement, while LAI Aripiprazole also exhibited positive outcomes in individuals with BPD and Substance Abuse. Additionally, Palomares et al. (2015) found that palmitate paliperidone LAI reduced impulsive-disruptive behaviors and enhanced overall functioning in BPD patients. Carmona et al. (2021) compared oral and LAI antipsychotics and concluded that LAIs may have a role to play in the management of BPD.
Conclusions
Treatment with LAIs may play an important role in clinical and functional improvement in BPD patients.
The population ageing is a reality associated with an increase in prevalence of Dementia. The use of benzodiazepines is often postulated as a risk factor in these syndromes.
Contrary to recommendations for its short-time use, long-term and chronic use are common, with an estimated 8,7% of elderly people in the US taking benzodiazepines.
Objectives
To clarify the most recent evidence on the use of benzodiazepines and the risk of developing dementia.
Methods
Non-systematic review of literature, using PubMed as database and filtering the results for meta-analysis.
Results
Four articles were included in this review.
Zhong G et al. concluded that risk of dementia increased in consumers of benzodiazepines and it was associated with higher doses.
In turn, AlDawasari A et al., when trying to clarify the use of different sedative-hypnotic drugs, found and increased risk with the consumption of benzodiazepines. After exclusion of articles with confounders and adjustment for protopathic bias, the risk was not maintained.
Lucchetta RC et al. concluded that the risk exists but without inferring differences between doses or duration of action.
Finally, Penninkilampi R e Eslick GD investigated this association, after controlling for the protopathic bias, concluding, contrary to AlDawasari et al., that the association benzodiazepines consumption and dementia do not result from this bias.
Conclusions
We cannot draw robust and concrete conclusions between benzodiazepines consumption and the pathogenesis of dementia because not only is the literature limited, but results are also heterogeneous.
However, these prescriptions must be carried out cautiously, especially in the elderly, due to the known adverse effects associated with them.
Develop and implement a system in the Veterans Health Administration (VA) to alert local medical center personnel in real time when an acute- or long-term care patient/resident is admitted to their facility with a history of colonization or infection with a multidrug-resistant organism (MDRO) previously identified at any VA facility across the nation.
Methods:
An algorithm was developed to extract clinical microbiology and local facility census data from the VA Corporate Data Warehouse initially targeting carbapenem-resistant Enterobacterales (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). The algorithm was validated with chart review of CRE cases from 2010-2018, trialed and refined in 24 VA healthcare systems over two years, expanded to other MDROs and implemented nationwide on 4/2022 as “VA Bug Alert” (VABA). Use through 8/2023 was assessed.
Results:
VABA performed well for CRE with recall of 96.3%, precision of 99.8%, and F1 score of 98.0%. At the 24 trial sites, feedback was recorded for 1,011 admissions with a history of CRE (130), MRSA (814), or both (67). Among Infection Preventionists and MDRO Prevention Coordinators, 338 (33%) reported being previously unaware of the information, and of these, 271 (80%) reported they would not have otherwise known this information. By fourteen months after nationwide implementation, 113/130 (87%) VA healthcare systems had at least one VABA subscriber.
Conclusions:
A national system for alerting facilities in real-time of patients admitted with an MDRO history was successfully developed and implemented in VA. Next steps include understanding facilitators and barriers to use and coordination with non-VA facilities nationwide.
Sucrose yield in sugarcane is a complex process regulated by both environmental and endogenous factors. However, the metabolic balance driving vegetative growth and sucrose accumulation remains poorly understood. Herein, we carried out a comprehensive assessment of carbohydrate dynamics throughout the crop cycle in two sugarcane varieties varying in biomass production, evaluating the carbon metabolism in both leaves and stalks. Our data revealed that the decline in photosynthetic rates during sugarcane maturation is associated not only to accumulation of sugars in leaves but also due to stomatal and non-stomatal limitations. We found that metabolic processes in leaves and stalks were intrinsically linked. While IACSP94-2094 had higher stalk sucrose concentration than IACSP95-5000, this latter produced more biomass. Compared to IACSP95-5000, IACSP94-2094 showed higher sucrose phosphate synthase (SPS) activity in leaves and stalks, along with lower soluble acid invertase (SAI) activity in leaves during the maximum growth stage. Interestingly, IACSP94-2094 also exhibited higher stalk SPS activity and lower stalk SAI activity than IACSP95-5000 during maturation. High biomass production by IACSP95-5000 was associated with higher sucrose synthase (SuSy) and SAI activity in leaves and higher SuSy and soluble neutral invertase (SNI) activity in stalks when compared to IACSP94-2094 during the maximum growth. Despite the contrasting strategies, both varieties displayed similar total sucrose yield, a balance between sucrose concentration and biomass production. This phenomenon implies the presence of a compensatory mechanism in sugarcane, with high biomass production compensating low sucrose accumulation and vice versa.