Development of collagenous scaffolds for wound healing: characterization and in vivo analysis.

The development of wound dressings from biomaterials has been the subject of research due to their unique structural and functional characteristics. Proteins from animal origin, such as collagen and chitosan, act as promising materials for applications in injuries and chronic wounds, functioning as a repairing agent. This study aims to evaluate in vitro effects of scaffolds with different formulations containing bioactive compounds such as collagen, chitosan, N-acetylcysteine (NAC) and ε-poly-lysine (ε-PL). We manufactured a scaffold made of a collagen hydrogel bioconjugated with chitosan by crosslinking and addition of NAC and ε-PL. Cell viability was verified by resazurin and live/dead assays and the ultrastructure of biomaterials was evaluated by SEM. Antimicrobial sensitivity was assessed by antibiogram. The healing potential of the biomaterial was evaluated in vivo, in a model of healing of excisional wounds in mice. On the 7th day after the injury, the wounds and surrounding skin were processed for evaluation of biochemical and histological parameters associated with the inflammatory process. The results showed great cell viability and increase in porosity after crosslinking while antimicrobial action was observed in scaffolds containing NAC and ε-PL. Chitosan scaffolds bioconjugated with NAC/ε-PL showed improvement in tissue healing, with reduced lesion size and reduced inflammation. It is concluded that scaffolds crosslinked with chitosan-NAC-ε-PL have the desirable characteristics for tissue repair at low cost and could be considered promising biomaterials in the practice of regenerative medicine.

Covalency versus magnetic axiality in Nd molecular magnets: Nd-photoluminescence, strong ligand-field, and unprecedented nephelauxetic effect in fullerenes NdM2N@C80 (M = Sc, Lu, Y).

Nd-based nitride clusterfullerenes NdM2N@C80 with rare-earth metals of different sizes (M = Sc, Y, Lu) were synthesized to elucidate the influence of the cluster composition, shape and internal strain on the structural and magnetic properties. Single crystal X-ray diffraction revealed a very short Nd-N bond length in NdSc2N@C80. For Lu and Y analogs, the further shortening of the Nd-N bond and pyramidalization of the NdM2N cluster are predicted by DFT calculations as a result of the increased cluster size and a strain caused by the limited size of the fullerene cage. The short distance between Nd and nitride ions leads to a very large ligand-field splitting of Nd3+ of 1100-1200 cm-1, while the variation of the NdM2N cluster composition and concomitant internal strain results in the noticeable modulation of the splitting, which could be directly assessed from the well-resolved fine structure in the Nd-based photoluminescence spectra of NdM2N@C80 clusterfullerenes. Photoluminescence measurements also revealed an unprecedentedly strong nephelauxetic effect, pointing to a high degree of covalency. The latter appears detrimental to the magnetic axiality despite the strong ligand field. As a result, the ground magnetic state has considerable transversal components of the pseudospin g-tensor, and the slow magnetic relaxation of NdSc2N@C80 could be observed by AC magnetometry only in the presence of a magnetic field. A combination of the well-resolved magneto-optical states and slow relaxation of magnetization suggests that Nd clusterfullerenes can be useful building blocks for magneto-photonic quantum technologies.

Tumor-localized interleukin-2 and interleukin-12 combine with radiation therapy to safely potentiate regression of advanced malignant melanoma in pet dogs.

The clinical use of interleukin-2 and -12 cytokines against cancer is limited by their narrow therapeutic windows due to on-target, off-tumor activation of immune cells when delivered systemically. Engineering IL-2 and IL-12 to bind to extracellular matrix collagen allows these cytokines to be retained within tumors after intralesional injection, overcoming these clinical safety challenges. While this approach has potentiated responses in syngeneic mouse tumors without toxicity, the complex tumor-immune interactions in human cancers are difficult to recapitulate in mouse models of cancer. This has driven an increased role for comparative oncology clinical trials in companion (pet) dogs with spontaneous cancers that feature analogous tumor and immune biology to human cancers. Here, we report the results from a dose-escalation clinical trial of intratumoral collagen-binding IL-2 and IL-12 cytokines in pet dogs with malignant melanoma, observing encouraging local and regional responses to therapy that may suggest human clinical benefit with this approach.

Determinants of multimorbidity in low- and middle-income countries: A systematic review of longitudinal studies and discovery of evidence gaps.

Multimorbidity-the coexistence of at least two chronic health conditions within the same individual-is an important global health challenge. In high-income countries (HICs), multimorbidity is dominated by non-communicable diseases (NCDs); whereas, the situation may be different in low- and middle-income countries (LMICs), where chronic communicable diseases remain prominent. The aim of this systematic review was to identify determinants (including risk and protective factors) and potential mechanisms underlying multimorbidity from published longitudinal studies across diverse population-based or community-dwelling populations in LMICs. We systematically searched three electronic databases (Medline, Embase, and Global Health) using pre-defined search terms and selection criteria, complemented by hand-searching. All titles, abstracts, and full texts were independently screened by two reviewers from a pool of four researchers. Data extraction and reporting were according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality and risk of bias assessment was performed using the Newcastle-Ottawa Scale for cohort studies. Data were summarized using narrative synthesis. The search yielded 1782 records. Of the 52 full-text articles included for review, 8 longitudinal population-based studies were included for final data synthesis. Almost all studies were conducted in Asia, with only one from South America and none from Africa. All studies were published in the last decade, with half published in the year 2021. The definitions used for multimorbidity were heterogeneous, including 3-16 chronic conditions per study. The leading chronic conditions were heart disease, stroke, and diabetes, and there was a lack of consideration of mental health conditions (MHCs), infectious diseases, and undernutrition. Prospectively evaluated determinants included socio-economic status, markers of social inequities, childhood adversity, lifestyle behaviors, obesity, dyslipidemia, and disability. This review revealed a paucity of evidence from LMICs and a geographical bias in the distribution of multimorbidity research. Longitudinal research into epidemiological aspects of multimorbidity is warranted to build up scientific evidence in regions beyond Asia. Such evidence can provide a detailed picture of disease development, with important implications for community, clinical, and interventions in LMICs. The heterogeneity in study designs, exposures, outcomes, and statistical methods observed in the present review calls for greater methodological standardisation while conducting epidemiological studies on multimorbidity. The limited evidence for MHCs, infectious diseases, and undernutrition as components of multimorbidity calls for a more comprehensive definition of multimorbidity globally.

Trypanosoma cruzi P21 recombinant protein modulates Toxoplasma gondii infection in different experimental models of the human maternal-fetal interface.

Introduction: Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as Trypanosoma cruzi, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate T. gondii infection. Methods: In this sense, we aimed to investigate the impact of T. cruzi and recombinant P21 (rP21) on T. gondii infection in BeWo cells and human placental explants. Results: Our results showed that T. cruzi infection, as well as rP21, increases invasion and decreases intracellular proliferation of T. gondii in BeWo cells. The increase in invasion promoted by rP21 is dependent on its binding to CXCR4 and the actin cytoskeleton polymerization, while the decrease in proliferation is due to an arrest in the S/M phase in the parasite cell cycle, as well as interleukin (IL)-6 upregulation and IL-8 downmodulation. On the other hand, in human placental villi, rP21 can either increase or decrease T. gondii proliferation, whereas T. cruzi infection increases T. gondii proliferation. This increase can be explained by the induction of an anti-inflammatory environment through an increase in IL-4 and a decrease in IL-6, IL-8, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-α production. Discussion: In conclusion, in situations of coinfection, the presence of T. cruzi may favor the congenital transmission of T. gondii, highlighting the importance of neonatal screening for both diseases, as well as the importance of studies with P21 as a future therapeutic target for the treatment of Chagas disease, since it can also favor T. gondii infection.

Subjective memory complaints: Prevalence, associated factors and sex differences in the ELSI-Brazil study.

BACKGROUND: Subjective memory complaints (SMCs) are a possible prodrome of cognitive decline but are understudied in low- and middle-income countries (LMIC). We aimed to estimate the prevalence of SMCs in a large, nationally representative sample of older adults from Brazil and to identify sociodemographic and health-related factors that are associated with SMCs independently of objective memory. METHODS: Baseline data (n = 7831) from the ELSI-Brazil study, a national representative sample of adults aged 50 and over. They were asked to rate their memory and then divided into two groups - having or not having SMCs. Logistic regression models were used to estimate the association of demographic characteristics, health related factors, objective memory performance and disability in basic (b-ADL), instrumental (i-ADL), and advanced (a-ADL) activities of daily living associated with SMCs. Whether sex was an effect modifier of the association between age and objective memory performance and SMCs was also tested. RESULTS: Of the sample, 42% (95% CI; 39.9-43.9) had SMCs, and it was higher among women (46.9%) than men (35.9%). SMC prevalence decreased with age among women and increased among men, and for both it decreased with better cognitive performance. Fully adjusted logistic regression model showed that older age, higher education, higher b-ADL scores, and better cognitive performance were associated with decreased SMCs, while being female, with higher number of chronic conditions, higher i-ADL scores, worst self-rated health, and an increased number of depressive symptoms were associated with increased SMCs. However, the interaction test (p < 0.001) confirmed that increased age was associated with decreased SMCs only among women, and that better objective memory performance was associated with decreased SMCs only among men. CONCLUSIONS: SMCs are common in the Brazilian older population and are associated with health and sociodemographic factors, with different patterns between men and women. There is a need for future studies looking at the cognitive trajectory and dementia risk in older adults with subjective cognitive complaints.

Efficacy and safety of ketamine for the treatment of depressive symptoms in palliative care: a systematic review

Objectives: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. Methods: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. Results: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. Conclusion: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.

Longitudinal invariance of psychotic experiences in children and adolescents: What do the data tell us?

BACKGROUND: Psychotic experiences are common in adults, adolescents, and children. While usually self-limited, they can indicate psychosis proneness when persistent. The Community Assessment of Psychic Experiences (CAPE) measures lifetime psychotic experiences in three dimensions. The 20-item subscale addressing positive symptoms (CAPE-positive) is the most widely used. No study investigated its measurement invariance across timepoints during childhood and adolescence. This step is required to conduct reliable comparisons in longitudinal studies with different age groups. METHODS: We used data from the Brazilian High-Risk Cohort, which enrolled 2511 individuals aged 6-12 years from public schools for the baseline evaluation. A 3-year follow-up assessment evaluated 1880 participants. Subjects were rated with the CAPE-positive and we performed, at each wave, a Multigroup Confirmatory Factor Analysis testing Exploratory and Confirmatory Factor Analysis models identified in a previous systematic review, to assess longitudinal invariance. RESULTS: A three-factor solution was the best fitting model, comprising Persecutory Ideation, Bizarre Experiences and Perceptual Abnormalities. The longitudinal invariance analysis of the best-fit model was unsatisfactory, achieving only the metric level of invariance. CONCLUSIONS: Our findings suggest that the CAPE-positive scale has good model fit indices for each evaluated time point individually (children and adolescents), but it is not invariant over time. Identifying which factors affect CAPE latent structure at different time points can improve our understanding of psychosis proneness and how to measure it.

The association of hearing loss with depressive symptoms and cognitive function among older people: Results from the Brazilian Longitudinal Study of Aging.

OBJECTIVES: Hearing loss, depression, and cognitive decline are common among older people. We investigated the association of hearing loss with depressive symptoms and cognitive function in a nationally representative sample of people aged 50+ in Brazil. METHODS: Data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil) included information on self-reported hearing loss, hearing aid use (effective or not effective), depressive symptoms (CES-D-8), and a global cognitive score (composed of immediate and late recall, verbal fluency, orientation and prospective memory) in a sample of 9412 individuals. Multiple linear regression was used to estimate the association of hearing loss and hearing aid use with both depressive symptoms and cognitive performance. The analyses were conducted with 7837 participants with complete data, and then repeated with data from the whole sample after multiple imputation. RESULTS: Compared to those without hearing loss, those with hearing loss were more likely to have a higher number of depressive symptoms (ß: 0.53 (0.40-0.67) p < 0.001) but not worse cognitive performance (ß: -0.01 (-0.03 to 0.19) p = 0.631). Among those with hearing loss, the use of hearing aid was neither associated with cognitive performance (ß: -0.08 (-0.19 to 0.03) p = 0.169) or depressive symptoms (ß: -0.42 (-0.98 to 0.14) p = 0.143); its effective use was associated with less depressive symptoms (ß: -0.62 (-1.23 to -0.01) p = 0.045) but not worse cognitive performance (ß: -0.15 (-0.030 to 0.03) p = 0.057). Sensitivity analyses revealed that hearing loss is associated with a worse performance in two non-amnestic cognitive domains. CONCLUSIONS: Hearing loss may negatively affect specific cognitive domains and depressive symptoms among older people, and the use of a hearing aid may mitigate the association with depressive symptoms.

Efficacy and safety of ketamine for the treatment of depressive symptoms in palliative care: A systematic review.

OBJECTIVES: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. METHODS: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. RESULTS: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. CONCLUSIONS: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.

Determinants and prognostic value of in-hospital infection in patients waiting for permanent pacemaker implantation.

BACKGROUND: In-hospital delays in permanent cardiac pacemaker (PPM) implantation are common and may result in in-hospital infection among patients waiting for PPM implantation (pre-PPM-HI). This study investigated the predictors and prognostic impact of these events. METHODS: We retrospectively evaluated 905 consecutive patients (68.2 ± 16.0 years; 54% males) who underwent PPM implantation. Clinical characteristics, pre-PPM-HI and 30-day mortality were recorded and a risk score for pre-PPM-HI was generated using multivariable logistic regression coefficients. RESULTS: Eigthy-nine patients (10% of the sample) developed pre-PPM-HI. Multivariable logistic regression analysis identified urinary catheter use, complete atrioventricular block, implantation of temporary pacemaker and diabetes mellitus as independent predictors of pre-PPM-HI. The generated score (range 0-10.1) played a better role in predicting pre-PPM-HI than individual factors, yielding an area under the curve [95%CI] of 0.754 [0.705-0.803]. Patients with score ≥ 7.5 had 18-fold greater risk of developing pre-PPM-HI than those with score < 2.5. Furthermore, multivariable Cox-regression analysis showed that patients who developed pre-PPM-HI had greater 30-day mortality after PPM implantation (hazard ratio [95%CI] = 2.90 [1.18-7.16], p = 0.021) compared with their counterparts. CONCLUSIONS: This study reveals that pre-PPM-HI is an independent predictor of early mortality after PPM implantation. In addition, a clinical score developed from simple clinical variables accurately identified patients at high risk of pre-PPM-HI. In scenarios where delays in PPM implantation are unavoidable, such as reference hospitals with high demand, the use of this tool can potentially help in the hierarchy of patients and in the reduction of this adverse event.

In vitro anthelmintic activity of Lippia alba essential oil chemotypes against Haemonchus contortus.

The aim of the present study was to evaluate the effects of the essential oils of Lippia alba chemotypes carvone and citral on H. contortus. Chemical characterization was performed by means of gas chromatography coupled to mass spectrometry (GC/MS). The anthelmintic effects of the essential oils were assessed through the egg hatch test (EHT) and the adult worm motility test (AWMT) using a multidrug-resistant H. contortus Kokstad isolate. Confocal laser scanning microscopy (CLSM) of eggs and adults of H. contortus and scanning electron microscopy (SEM) of adults were performed after treatment with oils for qualitative observations of their effects. The carvone chemotype of L. alba (LaCV) presented 70% carvone, and the citral chemotype of L. alba (LaCT) presented 29.4% geranial and 20.4% neral, respectively. In the EHT, the EC50 values of LaCV and LaCT were 0.2 and 0.3 mg/mL, respectively. In AWMT, after 12 h of exposure to 2 mg/mL LaCV and 2 mg/mL LaCT, 100% of adult nematodes were immobile. CLSM showed changes in larval motility inside the egg caused by LaCV, while LaCT promoted changes in larval formation. In adults exposed to both chemotypes, alterations in the anterior portion of the oesophagus were observed. In SEM, morphological changes were observed in the buccal capsule and in the medial portion of H. contortus adults. It is concluded that the two essential oils of L. alba, the chemotypes carvone and citral, caused morphological changes and inhibited the hatching of eggs and the motility of adult H. contortus nematodes.

Childhood poverty and mental health disorders in early adulthood: evidence from a Brazilian cohort study.

BACKGROUND: We examined the association between childhood poverty and mental health disorders (MHD) in childhood and early adulthood. We also investigated whether the association between poverty in childhood and MHD is mediated by exposure to stressful life events (SLE). METHODS: We used data from a prospective community cohort of young people assessed at baseline (M = 9.7 years, SD = 1.9), first (M = 13.5 years, SD = 1.9), and second (M = 18.2 years, SD = 2.0) follow-ups (N = 1,590) in Brazil. Poverty was assessed using a standardized classification. Exposure to 20 different SLE was measured using the Life History instrument. Psychiatric diagnoses were evaluated using the Development and Well-Being Assessment. Latent growth models investigated the association between poverty at baseline and the growth of any MHD, externalizing, and internalizing disorders. Mediation models evaluated whether the association between childhood poverty and MHD in early adulthood was mediated by exposure to SLE. RESULTS: Poverty affected 11.4% of the sample at baseline and was associated with an increased propensity for presenting externalizing disorders in adolescence or early adulthood (standardized estimate = 0.27, p = 0.016). This association was not significant for any disorder or internalizing disorders. Childhood poverty increased the likelihood of externalizing disorders in early adulthood through higher exposure to SLE (OR = 1.07, 95 CI% 1.01-1.14). Results were only replicated among females in stratified analyses. CONCLUSIONS: Childhood poverty had detrimental consequences on externalizing MHD in adolescence, especially among females. Poverty and SLE are preventable risk factors that need to be tackled to reduce the burden of externalizing disorders in young people.

Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression.

BACKGROUND AND OBJECTIVE: Affective disorders account for most cases of suicide. The pharmacological arsenal to treat suicidality is limited and available agents take too long to take effect. A large body of evidence shows optimal results of ketamine for treating depression, but the evidence concerning suicidality has not been fully described. We report the first real-world study of severely depressed patients presenting with suicide ideation who were treated with repeated administration of subcutaneous esketamine. METHODS: We analyzed data from 70 acutely depressed subjects diagnosed with resistant major depressive disorder or bipolar depression. Subjects were administered subcutaneous esketamine once a week for 6 weeks. The primary efficacy endpoint, the change from baseline to 24-h post-administration 6 in the item 10 Montgomery-Åsberg Depression Rating Scale score, was analyzed using a mixed-effects repeated-measures model. RESULTS: There were significant effects for time on item 10 Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001) but not for a time × diagnosis interaction (p = 0.164) from baseline to the end of the study. Efficacy of esketamine did not differ between groups (major depressive disorder vs bipolar depression) at any timepoint. Statistical significance on suicidality scores was observed from 24 h after the first administration (p < 0.001), and a further reduction was observed with repeated administrations. Esketamine was safe and well tolerated. Mean heart rate remained stable during the administrations and the blood pressure increase was self-limited. CONCLUSIONS: Repeated subcutaneous esketamine administration had significant anti-suicidality effects in both major depressive disorder and bipolar groups, with a rapid onset of action and a good tolerability profile. Large randomized controlled trials are warranted to confirm these preliminary findings.

Childhood individual and family modifiable risk factors for criminal conviction: a 7-year cohort study from Brazil.

Crime is a major public problem in low- and middle-income countries (LMICs) and its preventive measures could have great social impact. The extent to which multiple modifiable risk factors among children and families influence juvenile criminal conviction in an LMIC remains unexplored; however, it is necessary to identify prevention targets. This study examined the association between 22 modifiable individual and family exposures assessed in childhood (5-14 years, n = 2511) and criminal conviction at a 7-year follow-up (13-21 years, n = 1905, 76% retention rate) in a cohort of young people in Brazil. Population attributable risk fraction (PARF) was computed for significant risk factors. Criminal convictions were reported for 81 (4.3%) youths. Although most children living in poverty did not present criminal conviction (89%), poverty at baseline was the only modifiable risk factor significantly associated with crime (OR 4.14, 99.8% CI 1.38-12.46) with a PARF of 22.5% (95% CI 5.9-36.1%). It suggests that preventing children's exposure to poverty would reduce nearly a quarter of subsequent criminal convictions. These findings highlight the importance of poverty in criminal conviction, as it includes several deprivations and suggest that poverty eradication interventions during childhood may be crucial for reducing crime among Brazilian youth.

Prolonged Outbreak of Carbapenem and Colistin-Resistant Klebsiella pneumoniae at a Large Tertiary Hospital in Brazil.

Multidrug-resistant gram-negative bacteria, such as carbapenem and colistin-resistant Klebsiella pneumoniae (ColR-CRKP), represent a major problem for health systems worldwide and have high lethality. This study investigated the genetic relationship, antimicrobial susceptibility profile, and resistance mechanisms to ColR-CRKP isolates from patients infected/colonized in a tertiary hospital in Salvador, Bahia/Brazil. From September 2016 to January 2018, 46 patients (56 ColR-CRKP positive cultures) were enrolled in the investigation but clinical and demographic data were obtained from 31 patients. Most of them were men (67.7%) and elderly (median age of 62 years old), and the median Charlson score was 3. The main comorbidities were systemic arterial hypertension (38.7%), diabetes (32.2%), and cerebrovascular disease (25.8%). The average hospitalization stay until ColR-CRKP identification in days were 35.12. A total of 90.6% used mechanical ventilation and 93.7% used a central venous catheter. Of the 31 patients who had the data evaluated, 12 had ColR-CRKP infection, and seven died (58.4%). Previous use of polymyxins was identified in 32.2% of the cases, and carbapenems were identified in 70.9%. The minimum inhibitory concentration (MIC) for colistin was > 16 µg/mL, with more than half of the isolates (55%) having a MIC of 256 µg/mL. The bla KPC gene was detected in 94.7% of the isolates, bla NDM in 16.0%, and bla GES in 1.7%. The bla OXA-48, bla VIM, and bla IMP genes were not detected. The mcr-1 test was negative in all 56 isolates. Alteration of the mgrB gene was detected in 87.5% (n = 49/56) of the isolates, and of these, 49.0% (24/49) had alteration in size probably due to IS903B, 22.4% (11/49) did not have the mgrB gene detected, 20.4% (10/49) presented the IS903B, 6.1% (3/49) had a premature stop codon (Q30*), and 2.1% (1/49) presented a thymine deletion at position 104 - 104delT (F35fs). The PFGE profile showed a monoclonal profile in 84.7% of the isolates in different hospital sectors, with ST11 (CC-258) being the most frequent sequence type. This study presents a prolonged outbreak of ColR-CRKP in which 83.9% of the isolates belonged to the same cluster, and 67.6% of the patients evaluated had not used polymyxin, suggesting the possibility of cross-transmission of ColR-CRKP isolates.

Longitudinal invariance of the positive and negative syndrome scale negative dimension in antipsychotic naïve first-episode schizophrenia.

AIM: Construct stability over time is required for reliable inference, but evidence regarding the longitudinal invariance of negative symptoms is still limited. Thus, we examined the longitudinal invariance of the negative dimension using the positive and negative syndrome scale (PANSS) in an antipsychotic-naïve first-episode schizophrenia sample at baseline and after 10 weeks. METHODS: Our study was conducted at a specialized early intervention service. PANSS ratings were analysed for 138 patients, and two different models were specified and tested: a unidimensional and a two-correlated factor solution. RESULTS: The unidimensional model fulfilled criteria for longitudinal invariance, whilst the two-correlated did not. CONCLUSION: Our study provides support for the PANSS negative unidimensional model use to evaluate negative symptoms' longitudinal change following first-episode schizophrenia.

The probability of response after each subcutaneous injection of esketamine in treatment-resistant depression.

INTRODUCTION: The administration of multiple esketamine doses has shown efficacy for unipolar and bipolar treatment-resistant depression (TRD). Nevertheless, the probability of responding or not after each dose in the real-world remains unknown. This study aimed to estimate it throughout four doses of esketamine, administrated via subcutaneous (SC). MATERIAL AND METHODS: We conducted a retrospective analysis of a case series of 70 patients with TRD who received treatment from the esketamine assistance program at Federal University of Sao Paulo, between April 2017 and December 2018. The SC injections were administrated weekly at a dose of 0.5-1.0mg/kg, in conjunction with patients' psychotropic drugs. Response was defined as a decrease of at least 50% in the Montgomery-Åsberg Depression Rating Scale between baseline and 24h after dose. We used hidden Markov modeling in order to estimate de probability of response after each esketamine injection. RESULTS: The probability of a patient that was a "non-responder" to become a "responder" following a SC injection of esketamine was 17.30% and the probability that this patient remains a "non-responder" was 82.70%. The probability of a patient that was a "responder" to remain as a "responder" was 95%. CONCLUSIONS: Patients with TRD who had not responded after the first dose of esketamine, still had a chance of responding after the subsequent dose administrated via SC.

A Clinical Rationale for Assessing the Impact of Childhood Sexual Abuse on Adjunctive Subcutaneous Esketamine for Treatment-Resistant Depression.

Background: A history of child sexual abuse (CSA) is related to higher suicide rates and poor treatment outcomes in depressed adult patients. Twenty years after the first study investigating the effects of ketamine/esketamine on depression and suicide, there is a lack of data on the CSA effects on this emerging treatment. Here, we assess the impact of CSA on adjunctive subcutaneous (SC) esketamine for treatment-resistant depression (TRD). Methods: A directed acyclic graphic (DAG) was designed to identify clinical confounders between CSA and esketamine predictors of response. The confounders were applied in a statistical model to predict depression symptom trajectory in a sample of 67 TRD outpatients. Results: The patient sample had a relatively high prevalence rate of CSA (35.82%). Positive family history of first-degree relatives with alcohol use disorder and sex were clinical mediators of the effects of esketamine in a CSA adult population. Overall, the presence of at least one CSA event was unrelated to esketamine symptom reduction. Conclusions: Unlike responses to conventional antidepressants and psychotherapy, CSA does not appear to predict poor response to esketamine.

Repeated subcutaneous esketamine for treatment-resistant depression: Impact of the degree of treatment resistance and anxiety comorbidity.

BACKGROUND: A large number of studies indicate that subanesthetic doses of ketamine induce a fast antidepressant effect. Limited studies have investigated the subcutaneous (SC) route, and it remains unclear for whom this treatment is most suitable. AIMS: The aim of this study was to examine the effect on depressive symptoms of repeated subanesthetic doses of SC esketamine in unipolar and bipolar treatment-resistant depression (TRD) and clinical predictors of response. METHODS: A retrospective analysis of 70 patients who received six SC esketamine doses weekly as an adjunctive treatment was carried out. Doses started at 0.5 mg/kg and it could be titrated up to 1 mg/kg, according to response. The primary outcome was reduction in depressive symptoms. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale scores at the end of treatment. Comparisons between groups were made through analysis of variance and treatment effects. RESULTS: At baseline, our sample presented with severe treatment resistance in 65.7%, as assessed by the Maudsley Staging Method (MSM), and 47.1% had anxiety disorder comorbidity. The response rate was 50%. A better outcome was predicted by mild and moderate MSM scores (OR = 3.162, p = 0.041) and anxiety disorder comorbidity (OR = 3.149, p = 0.028). CONCLUSIONS: Our results suggest that higher levels of treatment resistance may be associated with a poor response to SC esketamine. Unlike traditional pharmacotherapies, it might benefit those with poor prognosis such as patients with depression and comorbid anxiety. Therefore, future research could investigate whether esketamine should receive a more prominent place in the treatment algorithm for TRD.