Investigating temporal patterns of colorectal cancer incidence in Spain: a comprehensive analysis of age, period and cohort effects, 1990-2019.

AIM: This study aimed to evaluate how age, period, and cohort (A-P-C) impact colorectal cancer (CRC) incidence in Spain from 1990 to 2019. METHOD: Using data from the Global Burden of Disease Study 2019, we used joinpoint analysis to identify long-term trends and A-P-C modelling to quantify net drift, local drift, longitudinal age curves, and rate ratios (RRs) of period and cohort effects. RESULTS: CRC incidence increased steadily in Spain from 1990 to 2019, with a more significant rise in males than in females. The age standardized rates rose from 84.9 to 129.3 cases per 100,000 in males and from 56.9 to 70.3 cases per 100,000 in females. Joinpoint analysis revealed distinct patterns for men and women: male incidence showed three phases (a surge until 1995, a slowdown until 2012, and a subsequent decrease) while female incidence showed a single increase until 2011 and then stabilized. Local drifts increased in all age groups over 45, with stability in males under 45 and a decrease in females aged 30-39. The risk of CRC increased with age, with males consistently having a higher risk than females. The risk of CRC increased over time for both men and women but at different rates. The risk for cohorts born in the early to mid-20th century peaked in the 1960s and remained stable until the late 1990s. CONCLUSION: The increasing incidence of CRC in Spain, with distinct patterns by gender and birth cohort, underlines the importance of preventive strategies adapted to temporal and demographic variations to address this public health challenge.

Neuroleptic Malignant Syndrome Status Post Anoxic Brain Injury: A Case Presentation of Heightened Susceptibility in the Brain Injury Population.

Neuroleptic malignant syndrome (NMS), a potentially life-threatening neurological emergency characterized by muscle rigidity, altered mental status (AMS), autonomic instability, and hyperthermia, is most commonly precipitated by high-potency first-generation antipsychotics due to central dopamine receptor blockade. There is a heightened risk of NMS in animals with ischemic brain injury (IBI) or traumatic brain injury (TBI) due to the resulting death of dopaminergic neurons from injury and the dopamine receptor blockade elicited upon recovery. To the best of our knowledge, this will be the first documented case of a critically ill patient, with a history of prior exposure to antipsychotics, who suffered an anoxic brain injury with subsequent development of NMS after the initiation of haloperidol for the treatment of acute agitation. Further investigation is necessary to expand upon the existing literature suggesting the role of alternative agents, including amantadine, due to its impact on dopaminergic transmission, as well as dopamine and glutamine release. Furthermore, NMS can be difficult to diagnose due to variable clinical presentation and lack of absolute diagnostic criteria, which is further compounded with central nervous system (CNS) injury, where neurological abnormalities and AMS may be attributed to the injury, rather than a medication effect, especially in the early period. This case highlights the significance of prompt recognition with appropriate treatment of NMS in vulnerable and susceptible patients suffering from brain injury.

Impact of Psychiatry Clerkship Rotation in Attitudes Towards Mental Illness and Psychiatry as a Career Among Medical Students.

Background: Stigma associated with mental illness (MI) permeates many professions, including healthcare. Recognizing and correcting bias is critical in delivering impartial and beneficial healthcare for all patients. Early educational interventions providing exposure to individuals with MI have shown to be effective at reducing MI stigma. The primary aim of our study was to assess the impact of a psychiatry clerkship on attitudes to MI. A secondary aim was to determine if the psychiatry clerkship influenced medical students' perceptions of psychiatry as a career. Methods: A cohort of third-year medical students in Florida was invited to complete an online survey before and after participating in their first 4-week-long psychiatry clerkship during the 2021-2022 academic year. The voluntary, anonymous survey consisted of the Attitudes to Mental Illness Questionnaire (AMIQ) and a 3-item questionnaire on interest and knowledge in psychiatry. The Wilcoxon Sign-Rank test was used to determine statistical significance (P < .05) for pre- and post-clerkship values. Results: Among 39 invited students, 22 participated before (56.4%), and 23 participated after their psychiatry rotation (59.0%). Overall, there was a statistically significant increase in the perceived level of general interest in psychiatry (P = .027), psychiatry knowledge (P < .001), and career interest in psychiatry (P = .040). There was also a significant decrease in the stigmatized attitude score for depression and self-harm after their psychiatry rotation (P = .042). Finally, the participants initially showed the highest stigmatized attitude score for intravenous drug abuse among the 4 mental illnesses presented, which also included depression and suicidal ideation, alcohol use disorder, and schizophrenia. Conclusion: The findings suggest that a psychiatry clerkship provided a positive exposure to the field, enhanced medical students' overall interest in psychiatry, and positively impacted medical students' attitudes towards MI.

Gender Dysphoria Versus Acute Psychosis: Can One Properly Diagnose Gender Dysphoria Solely During Acute Psychosis?

Description Gender dysphoria occurs when a discrepancy between one's sex assigned at birth and one's gender identity causes distress or impairment in function, which can lead ultimately to seeking treatment in the forms of psychotherapy, hormonal therapy, and/or gender-affirming surgery. Clinical care guidelines also recommend pharmacological treatment of psychiatric comorbidities if indicated. A review of the current literature demonstrates comorbidity between gender dysphoria and psychosis, including cases of gender dysphoria with schizophrenia and the occurrence of gender dysphoria symptoms during manic or psychotic episodes. The existing literature has yet to specifically examine gender dysphoria amongst individuals with schizoaffective disorder. The authors present the first documented case of a clear pattern of gender identity variations coinciding solely with psychotic episodes during schizoaffective disorder, bipolar type. The authors postulate that gender dysphoria can co-occur with other psychiatric disorders or may correspond only during acute psychosis. The distinction is critical to make to ensure accurate diagnoses regarding whether gender dysphoria is a symptom only during an acute psychotic illness, or if there is a longer-standing concern as to the patient's gender identity and assignment. This distinction then also informs how to make the most appropriate treatment recommendations. The authors address the significance of understanding each patient's individual circumstances and deem this paramount to advancing transgender and gender non-binary health equity at every level of medical attention, focusing specifically on proper physician training and direct patient care.

A Case Report and Review: Charles Bonnet Syndrome Plus With Dementia.

Introduction: Charles Bonnet Syndrome (CBS) refers to visual hallucinations in visually impaired patients without psychiatric illness who are typically aware that their hallucinations are not real. Rare cases in the literature describe patients with atypical CBS, or CBS plus, who experience hallucinations in the context of sensory deficits but do not meet all of the criteria of a CBS diagnosis. These cases may include hallucinations in more than one sensory modality, including auditory hallucinations, which are thought to arise by a similar pathophysiology to that of the visual hallucinations in CBS. Unfortunately, the clinical criteria for atypical CBS are ambiguous, potentially explaining the rarity of the diagnosis. In addition, certain features of atypical CBS may make the condition particularly prone to misdiagnosis. Case Presentation: We report a case of atypical CBS in a 67-year-old white male patient presenting with visual and auditory hallucinations that were improved by reassurance. Alongside this case presentation, we provide a review of atypical CBS cases in the literature to compare the diverse features of the syndrome. For this review, we included cases of atypical CBS or CBS plus within the past 20 years for which we could obtain the full text. Conclusion: Clearer guidelines for the diagnosis of atypical CBS and greater attention to the disorder could substantially improve the management of patients presenting with hallucinations. A broader differential diagnosis including atypical CBS for elderly patients with new-onset hallucinations could help clinicians and patients avoid unnecessary medical workup and treatment.

Increased Readmission Rates in Younger Male Patients Due to Suicidal Risk in Newly Diagnosed Depressive Disorders After Initiation of Serotonin Reuptake Inhibitors.

Background Depressive disorders have a prevalence of 322 million people worldwide and are a leading cause of morbidity. These disorders can affect individuals of all ages and can present over time. Due to the diversity in the presentation of depressive disorders, vigilance towards depressive disorders can lead to more timely and effective treatment. Serotonin Selective Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) are the first lines of treatment for these disorders. Moreover, the United States Food and Drug Administration (FDA) issued a black-box warning for several antidepressants, stating an increased risk of suicidality in individuals under 25 years old. However, the placement of this black-box warning has been controversial. In this study, the authors aim to investigate if there is a relationship between the use of SSRI or SNRI on patients with newly diagnosed depressive disorder and hospital readmission due to suicide-related events.  Methods For this retrospective cohort study, de-identified data were obtained from the HCA Healthcare database by searching for patients newly diagnosed with depressive disorders and started on SSRIs or SNRIs. Patient data were evaluated for readmissions due to suicide-related events within 90 days of discharge from the hospital and establishing their initial SSRI/SNRI prescription.  Results After data was obtained and evaluated via statistical analysis, the variables with statistical significance were: age (p-value = 0.0164) and sex (p-value = 0.0150). These two were significantly associated with the rate of readmission: younger and male patients had an increased risk of readmission due to suicide-related events within 90 days of discharge after starting SSRI, or SNRI, to treat depressive disorders. Conclusion These results support the importance of monitoring patients started on SSRI or SNRI, with particularly careful consideration in depressed young male patients.

Melatonin in Traumatic Brain Injury and Cognition.

Traumatic brain injury (TBI) is a leading cause of long-term disability and mortality in young adults. The devastating effects of TBI on emotion regulation, executive functioning, and cognition have been well-established, and recent research links TBI as a risk factor for neurodegenerative diseases such as Alzheimer's disease. Despite an increased focus on the long-term cognitive dysfunction associated with TBI, research into potential treatments has not yet generated consistent successful results in human subjects. Many foundational studies have analyzed the cellular and molecular events involved in the inflammatory and healing processes following TBI, enhancing our understanding of the mechanisms that may contribute to the progression of dementia and cognitive decline in these patients. In this review, we will discuss the emergent research on melatonin within the framework of neuroinflammation and oxidative stress resulting from TBI and possibly preventing further sequelae such as Alzheimer's disease. A literature review was conducted using standard search strategies to query the PubMed database. The following search terms were used with qualifiers of various combinations: TBI, traumatic brain injury, melatonin, treatment, dementia, Alzheimer's, cognition, and neurodegeneration. Selected studies included meta-analyses, literature reviews, and randomized controlled trials (RCT) that evaluated melatonin's role as a potential therapy to prevent post-TBI neurodegeneration, specifically the development of dementia and deficits in memory and cognition. Three independent reviewers assessed all articles for eligibility. After assessment for eligibility, 11 total studies were included. Much of the available data on melatonin in TBI has highlighted its significant neuroprotective and antiinflammatory effects, which can be significant in fighting against the neuroinflammatory processes indicated in neurodegeneration. In animal models, immunohistochemistry and histopathology have allowed researchers to study measures of cell injury such as inflammatory cytokines, edema, and markers of oxidative stress. Though the effects of melatonin in TBI appear to be mediated through mostly indirect mechanisms on inflammatory processes, some research has explored potential mechanisms that could be specific to melatonin. Animal model studies support that melatonin treatment after TBI significantly improves cognition and behavioral outcomes. However, clinical studies with human subjects are scarce. Beyond the apparent general antiinflammatory and antioxidant actions of melatonin, a review of the evidence identified some preliminary research that has suggested the significance of melatonin receptors specifically in TBI. While there is some evidence to suggest that melatonin is able to reduce post-TBI cognitive decline as measured by subject performance on memory tasks, there is a lack of longitudinal data on whether melatonin decreases the risk of developing dementia after TBI. Considering melatonin therapy's promising preclinical data, favorable safety profile, and accessibility, further studies are warranted to assess the effects of melatonin as a post-TBI therapy on human subjects.

Acute Psychosis with Recurrent Neurocysticercosis: A Case Presentation.

Description Neurocysticercosis, a parasitic infection of the central nervous system (CNS) caused by the Taenia solium cestode, presents clinically with a large and diverse spectrum of symptomatology, dependent upon lesion number, locale and ensuing inflammatory response. To this date, there are only two documented cases of psychosis presenting in patients with neurocysticercosis, both of which were published in India. This case presentation depicts the first documented case of Psychotic Disorder Due to Another Medical Condition: Neurocysticercosis in the United States. The authors postulate that the atypical presentation of the neuropsychiatric instability with the aberrant recurrence of neurocysticercosis is predominantly attributable to the parasitic infection itself, along with its resultant cyst formation and inflammatory response. Further research is necessary to expand upon our knowledge and understanding of the neuropsychiatric effects and optimal management of neurocysticercosis, as well as its possible recurrent nature.

Structure-Based Design of an RNase Chimera for Antimicrobial Therapy.

Bacterial resistance to antibiotics urges the development of alternative therapies. Based on the structure-function of antimicrobial members of the RNase A superfamily, we have developed a hybrid enzyme. Within this family, RNase 1 exhibits the highest catalytic activity and the lowest cytotoxicity; in contrast, RNase 3 shows the highest bactericidal action, alas with a reduced catalytic activity. Starting from both parental proteins, we designed a first RNase 3/1-v1 chimera. The construct had a catalytic activity much higher than RNase 3, unfortunately without reaching an equivalent antimicrobial activity. Thus, two new versions were created with improved antimicrobial properties. Both of these versions (RNase 3/1-v2 and -v3) incorporated an antimicrobial loop characteristic of RNase 3, while a flexible RNase 1-specific loop was removed in the latest construct. RNase 3/1-v3 acquired both higher antimicrobial and catalytic activities than previous versions, while retaining the structural determinants for interaction with the RNase inhibitor and displaying non-significant cytotoxicity. Following, we tested the constructs' ability to eradicate macrophage intracellular infection and observed an enhanced ability in both RNase 3/1-v2 and v3. Interestingly, the inhibition of intracellular infection correlates with the variants' capacity to induce autophagy. We propose RNase 3/1-v3 chimera as a promising lead for applied therapeutics.

Gabapentin for Post-Hospitalization Alcohol Relapse Prevention; Should Gabapentin Be Considered for FDA Approval in the Treatment of Alcohol Use Disorder?: A Case Presentation and Literature Review.

Alcohol use disorder (AUD), a chronic condition that affects many people worldwide, is characterized most commonly by a preoccupation with alcohol, an irresistible craving for or the inability to control the consumption of alcohol, and the marked resultant disturbance it bestows upon one's life. Although a difficult and time-consuming condition to attempt to treat, there are currently three FDA-approved medications for AUD, including naltrexone, acamprosate, and disulfiram. However, literature points towards another agent, gabapentin, that may be efficacious in preventing relapse symptoms and cravings with enhanced effectivity in reducing post-hospitalization alcohol consumption behaviors. In this paper, we discuss a case presentation and literature review demonstrating the role of gabapentin in treating AUD and symptoms associated with alcohol withdrawal, along with its potential use in relapse prevention.

Positional scanning library applied to the human eosinophil cationic protein/RNase3 N-terminus reveals novel and potent anti-biofilm peptides.

Eradication of established biofilm communities of pathogenic bacteria is one of the pending challenges in the development of new antimicrobial agents. In particular, the dreaded nosocomial Pseudomonas aeruginosa forms microbial communities that offer an enhanced resistance to conventional antibiotics. Recently, we have described an engineered antimicrobial peptide derived from the human RNase3, also named the eosinophil cationic protein (ECP), RN3 (5-36), which combines bactericidal activity with high cell agglutination and lipopolysaccharide (LPS) affinity. Through a single replacement scan library using the SPOT methodology we have evaluated both the contribution of sequence positioning and amino acid singularity towards the peptide biological and physicochemical properties. Results indicate that the ECP N-terminus has already been extensively improved through evolution to provide high antimicrobial activity; hence most substitutions improving its antimicrobial performance are in detriment of safety towards host tissues. Only three positions were identified, occupied by polar residues on the first α-helix of the protein and replaceable by a hydrophobic residue, allowing an extended N-terminal patch that mediates bacterial agglutination. Among the best candidates, an Ile replacement proved best in improving the peptide therapeutic window. The novel engineered peptides encompass both the LPS-binding and aggregation-prone regions of parental ECP, providing the appropriate structural features for peptide attachment to the bacterial exopolysaccharide layer and bacterial cell membrane destabilization, thereby promoting biofilm removal at micro molar concentrations. We conclude that the novel engineered peptides are promising lead candidates against Gram-negative biofilms.

A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities.

Eradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular, Pseudomonas aeruginosa is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The RN3(5-17P22-36) peptide is a 30-mer derived from the eosinophil cationic protein (ECP), a host defense RNase secreted by eosinophils upon infection, with a wide spectrum of antipathogen activity. The protein displays high biofilm eradication activity that is not dependent on its RNase catalytic activity, as evaluated by using an active site-defective mutant. On the other hand, the peptide encompasses both the LPS-binding and aggregation-prone regions from the parental protein, which provide the appropriate structural features for the peptide's attachment to the bacterial exopolysaccharide layer and further improved removal of established biofilms. Moreover, the peptide's high cationicity and amphipathicity promote the cell membrane destabilization action. The results are also compared side by side with other reported AMPs effective against either planktonic and/or biofilm forms of Pseudomonas aeruginosa strain PAO1. The ECP and its derived peptide are unique in combining high bactericidal potency and cell agglutination activity, achieving effective biofilm eradication at a low micromolar range. We conclude that the designed RN3(5-17P22-36) peptide is a promising lead candidate against Gram-negative biofilms.