Duration of untreated illness predicts 3-year outcome in patients with obsessive-compulsive disorder: A real-world, naturalistic, follow-up study

Duration of untreated illness (DUI) is a predictor of outcome in psychotic and affective disorders. The few available data on the effect of DUI in obsessive-compulsive disorder (OCD) suggest an association between longer DUI and poorer response to treatments. This is a real-world, naturalistic, follow-up study evaluating the impact of DUI on long-term clinical outcomes. The sample consists of 83 outpatients with OCD with a mean DUI of 7.3 (5.8) years. Patients with symmetry/ordering cluster symptoms were younger at onset of the disease (20.4 ± 7.9 vs. 27.8 ± 10.6; p<.05, d = 0.79), had a longer duration of the illness (10.1 ± 4.6 vs. 6.8 ± 4.6, p<.05; d = 0.53) and a longer DUI (7.9 ± 6.5 vs. 5.4 ± 3.6, p<.05, d = 0.49) compared to patients not presenting with those symptoms. Fifty-nine patients completed the follow-up, and 33.9% (N = 20) met the criteria for partial remission, scoring <15 at the Y-BOCS for at least eight weeks. Patients in partial remission for more than 40% of the follow-up were defined as “good outcome” and they had a significantly shorter DUI compared to patients with “poor outcome”. Access to adequate treatments is highly delayed in patients with OCD. DUI is strongly associated with poor treatment outcomes. Therefore, strategies to ensure an early diagnosis and treatment are needed

Natural cycle results in lower implantation failure than ovarian stimulation in advanced-age poor responders undergoing IVF. fertility outcomes from 585 patients

To compare pregnancy rate and implantation rate in poor responder women, aged over 40 years, who underwent natural cycle versus conventional ovarian stimulation. This is a retrospective single-center cohort study conducted at the GENERA IVF program, Rome, Italy, between September 2012 and December 2018, including only poor responder patients, according to Bologna criteria, of advanced age, who underwent IVF treatment through Natural Cycle or conventional ovarian stimulation. Between September 2012 and December 2018, 585 patients were included within the study. Two hundred thirty patients underwent natural cycle and 355 underwent conventional ovarian stimulation. In natural cycle group, both pregnancy rate per cycle (6.25 vs 12.89%, respectively, p = 0.0001) and pregnancy rate per patient101 with at least one embryo-transfer (18.85 vs 28.11% respectively, p = 0.025) resulted significant reduced. Pregnancy rate per patient managed with conventional ovarian stimulation resulted not significantly different compared with natural cycle (19.72 vs 15.65% respectively, p = 0.228), but embryo implantation rate was significantly higher in patients who underwent natural cycle rather than patient subjected to conventional ovarian stimulation (13 vs 8.28% respectively, p = 0.0468). No significant difference could be detected among the two groups in terms of abortion rate (p = 0.2915) or live birth pregnancy (p = 0.2281). Natural cycle seems to be a valid treatment in patients over 40 years and with a low ovarian reserve, as an alternative to conventional ovarian stimulation

Tailored enrichment strategy detects low abundant small noncoding RNAs in HIV-1 infected cells

BACKGROUND: The various classes of small noncoding RNAs (sncRNAs) are important regulators of gene expression across divergent types of organisms. While a rapidly increasing number of sncRNAs has been identified over recent years, the isolation of sncRNAs of low abundance remains challenging. Virally encoded sncRNAs, particularly those of RNA viruses, can be expressed at very low levels. This is best illustrated by HIV-1 where virus encoded sncRNAs represent approximately 0.1-1.0% of all sncRNAs in HIV-1 infected cells or were found to be undetected. Thus, we applied a novel, sequence targeted enrichment strategy to capture HIV-1 derived sncRNAs in HIV-1 infected primary CD4+ T-lymphocytes and macrophages that allows a greater than 100-fold enrichment of low abundant sncRNAs. RESULTS: Eight hundred and ninety-two individual HIV-1 sncRNAs were cloned and sequenced from nine different sncRNA libraries derived from five independent experiments. These clones represent up to 90% of all sncRNA clones in the generated libraries. Two hundred and sixteen HIV-1 sncRNAs were distinguishable as unique clones. They are spread throughout the HIV-1 genome, however, forming certain clusters, and almost 10% show an antisense orientation. The length of HIV-1 sncRNAs varies between 16 and 89 nucleotides with an unexpected peak at 31 to 50 nucleotides, thus, longer than cellular microRNAs or short-interfering RNAs (siRNAs). Exemplary HIV-1 sncRNAs were also generated in cells infected with different primary HIV-1 isolates and can inhibit HIV-1 replication. CONCLUSIONS: HIV-1 infected cells generate virally encoded sncRNAs, which might play a role in the HIV-1 life cycle. Furthermore, the enormous capacity to enrich low abundance sncRNAs in a sequence specific manner highly recommends our selection strategy for any type of investigation where origin or target sequences of the sought-after sncRNAs are known

Low penetrance and effect on protein secretionof LGI1 mutations causing autosomal dominantlateral temporal epilepsy

Purpose: To describe the clinical and genetic findings of four families with autosomal dominant lateral temporal epilepsy. Methods: A personal and family history was obtained from each affected and unaffected subject along with a physical and neurologic examination. Routine electroencephalography and magnetic resonance imaging (MRI) studies were performed in almost all patients. DNAs from family members were screened for LGI1 mutations. The effects of mutations on Lgi1 protein secretion were determined in transfected culture cells. Key Findings: The four families included a total of 11 patients (two deceased), six of whom had lateral temporal epilepsy with auditory aura. Age at onset was in the second decade of life; seizures were well controlled by antiepileptic treatment and MRI studies were normal. We found two pathogenic LGI1 mutations with uncommonly low penetrance: the R136W mutation, previously detected in a sporadic case with telephone-induced partial seizures, gave rise to the epileptic phenotype in three of nine mutation carriers in one family; the novel C179R mutation caused epilepsy in an isolated patient from a family where the mutation segregated. Another novel pathogenic mutation, I122T, and a nonsynonymous variant, I359V, were found in the two other families. Protein secretion tests showed that the R136W and I122T mutations inhibited secretion of the mutant proteins, whereas I359V had no effect on protein secretion; C179R was not tested, because of its predictable effect on protein folding. Significance: These findings suggest that some LGI1 mutations may have a weak penetrance in families with complex inheritance pattern, or isolated patients, and that the protein secretion test, together with other predictive criteria, may help recognize pathogenic LGI1 mutations. KEY WORDS: Autosomal dominant lateral temporal epilepsy, LGI1, Mutation, Low penetrance, Protein secretion

The potential impact of enhanced hygienic measures during the COVID-19 outbreak on hospital-acquired infections: A pragmatic study in neurological units

Objective: Hospital-acquired infections (HAIs) are frequent complications among acute patients hospitalized in neurological units, especially among those hospitalized for stroke. This study aimed to investigate if enhanced hygienic measures, including the systematic use of personal protective equipment (PPE), determined a decrease in HAI during the recent COVID-19 outbreak in “COVID-free” neurological units. Methods: Patients hospitalized in neurology and stroke units of Policlinico Umberto I Hospital in Rome from March 8, 2020 and discharged prior to May 31, 2020 were included in the study and compared with patients hospitalized during the same period in 2019. Results: A total of 319 patients were included in the study (n = 103 in 2020, n = 216 in 2019). Among patients hospitalized in 2019, the incidence of HAIs was 31.5% (95% confidence interval (CI): 0.25–0.38), compared with 23.3% (95% CI: 0.15–0.32) in 2020 (p = 0.12). Multivariable logistic regression showed that hospitalization during 2020 was independently associated with a lower risk of HAIs (odds ratio: 0.34, 95% CI:0.16–0.71, p = 0.004). Poisson regression models showed that hospitalization during 2020 was also independently associated with both a lower number of HAIs (relative risk [RR]: 0.56, 95% CI:0.38–0.81, p = 0.01) and a lower number of prescribed antibiotics per patient (RR: 0.66, 95% CI: 0.49–0.87, p = 0.02). Conclusion: Our study design provides evidence regarding the impact of stricter hygienic measures, such as increased PPE use, on HAIs. Larger studies are needed to support the extension of preventive measures even after the COVID-19 outbreak in order to limit the occurrence of HAIs

Multiple detection and spread of novel strains of the SARS-CoV-2 B.1.177 (B.1.177.75) lineage that test negative by a commercially available nucleocapsid gene real-time RT-PCR

Several lineages of SARS-CoV-2 are currently circulating worldwide. During SARS-CoV-2 diagnostic activities performed in Abruzzo region (central Italy) several strains belonging to the B.1.177.75 lineage tested negative for the N gene but positive for the ORF1ab and S genes (+/+/- pattern) by the TaqPath COVID-19 CE-IVD RT-PCR Kit manufactured by Thermofisher. By sequencing, a unique mutation, synonymous 28948C > T, was found in the N-negative B.1.177.75 strains. Although we do not have any knowledge upon the nucleotide sequences of the primers and probe adopted by this kit, it is likely that N gene dropout only occurs when 28948C > T is coupled with 28932C > T, this latter present, in turn, in all B.1.177.75 sequences available on public databases. Furthermore, epidemiological analysis was also performed. The majority of the N-negative B.1.177.75 cases belonged to two clusters apparently unrelated to each other and both clusters involved young people. However, the phylogeny for sequences containing the +/+/- pattern strongly supports a genetic connection and one common source for both clusters. Though, genetic comparison suggests a connection rather than indicating the independent emergence of the same mutation in two apparently unrelated clusters. This study highlights once more the importance of sharing genomic data to link apparently unrelated epidemiological clusters and to, remarkably, update molecular tests

Seizures in autoimmune encephalitis: Findings from an EEG pooled analysis

Purpose: Seizures are common in autoimmune encephalitis (AE), and an extensive work-up is required to exclude alternative etiologies. The aim of our study was to identify possible clinical/EEG peculiarities suggesting the immune-mediated origin of late-onset seizures. Methods: Thirty patients diagnosed with AE (19 men, median age 68 years, 18 seronegative) were included. Overall 212 video-electroencephalographic (EEG) and 31 24-h ambulatory EEG (AEEG) recordings were retrospectively reviewed. Posterior dominant rhythm, interictal epileptiform discharges (IEDs), clinical (CSs) and subclinical seizures (SCSs) were analyzed. Results: Six-hundred-nineteen ictal events were recorded in 19/30 subjects, mostly (568/619) during AE acute stage. Among ten patients with CSs other than faciobrachial dystonic seizures, 7 showed prominent autonomic and emotional manifestations. SCSs were detected in 11 subjects, mainly via AEEG (260/287 SCSs vs 150/332 CSs, p < 0.001). Eight patients presented seizures during hyperventilation. IEDs, documented in 21 cases, were bilateral in 14 and focal temporal in 13. Multiple ictal EEG patterns were detected in 9/19 patients, 6 of whom had both CSs and SCSs, bilateral asynchronous seizures and ictal activities arising from temporal and extra-temporal regions. No correlation was found between the lateralization of MRI alterations and that of EEG findings. Conclusion: Our study confirms that adult-onset, high frequency focal seizures with prominent autonomic and emotional manifestations should be investigated for AE. Multiple ictal EEG patterns could represent a ‘red flag’, reflecting a widespread neuronal excitability related to the underlying immune-mediated process. Finally, our work enhances the crucial role of long-lasting EEG monitoring in revealing subclinical and relapsing seizures

The Impact of Quarantine and Physical Distancing Following COVID-19 on Mental Health : Study Protocol of a Multicentric Italian Population Trial

The COVID-19 pandemic and its related containment measures-mainly physical distancing and isolation-are having detrimental consequences on the mental health of the general population worldwide. In particular, frustration, loneliness, and worries about the future are common reactions and represent well-known risk factors for several mental disorders, including anxiety, affective, and post-traumatic stress disorders. The vast majority of available studies have been conducted in China, where the pandemic started. Italy has been severely hit by the pandemic, and the socio-cultural context is completely different from Eastern countries. Therefore, there is the need for methodologically rigorous studies aiming to evaluate the impact of COVID-19 and quarantine measures on the mental health of the Italian population. In fact, our results will help us to develop appropriate interventions for managing the psychosocial consequences of pandemic. The "COVID-IT-mental health trial" is a no-profit, not-funded, national, multicentric, cross-sectional population-based trial which has the following aims: a) to evaluate the impact of COVID-19 pandemic and its containment measures on mental health of the Italian population; b) to identify the main areas to be targeted by supportive long-term interventions for the different categories of people exposed to the pandemic. Data will be collected through a web-platform using validated assessment tools. Participants will be subdivided into four groups: a) Group 1-COVID-19 quarantine group. This group includes the general population which are quarantined but not isolated, i.e., those not directly exposed to contagion nor in contact with COVID-19+ individuals; b) Group 2-COVID-19+ group, which includes isolated people directly/indirectly exposed to the virus; c) Group 3-COVID-19 healthcare staff group, which includes first- and second-line healthcare professionals; d) Group 4-COVID-19 mental health, which includes users of mental health services and all those who had already been diagnosed with a mental disorder. Mental health services worldwide are not prepared yet to manage the short- and long-term consequences of the pandemic. It is necessary to have a clear picture of the impact that this new stressor will have on mental health and well-being in order to develop and disseminate appropriate interventions for the general population and for the other at-risk groups