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In Gram-negative bacteria, periplasmic domains in inner membrane proteins are cotranslationally translocated across the inner membrane through the SecYEG translocon. To what degree such domains also start to fold cotranslationally is generally difficult to determine using currently available methods. Here, we apply Force Profile Analysis (FPA) - a method where a translational arrest peptide is used to detect folding-induced forces acting on the nascent polypeptide - to follow the cotranslational translocation and folding of the large periplasmic domain of the E. coli inner membrane protease LepB in vivo. Membrane insertion of LepB's two N-terminal transmembrane helices is initiated when their respective N-terminal ends reach 45-50 residues away from the peptidyl transferase center (PTC) in the ribosome. The main folding transition in the periplasmic domain involves all but the ~15 most C-terminal residues of the protein and happens when the C-terminal end of the folded part is ~70 residues away from the PTC; a smaller putative folding intermediate is also detected. This implies that wildtype LepB folds post-translationally in vivo, and shows that FPA can be used to study both co- and post-translational protein folding in the periplasm.Pitch accents are local pitch patterns that convey differences in word prominence and modulate the information structure of the discourse. Despite the importance to discourse in languages like English, neural processing of pitch accents remains understudied. The current study investigates the neural processing of pitch accents by native and non-native English speakers while they are listening to or ignoring 45 min of continuous, natural speech. Leveraging an approach used to study phonemes in natural speech, we analyzed thousands of electroencephalography (EEG) segments time-locked to pitch accents in a prosodic transcription. The optimal neural discrimination between pitch accent categories emerged at latencies between 100 and 200 ms. During these latencies, we found a strong structural alignment between neural and phonetic representations of pitch accent categories. In the same latencies, native listeners exhibited more robust processing of pitch accent contrasts than non-native listeners. However, these group differences attenuated when the speech signal was ignored. We can reliably capture the neural processing of discrete and contrastive pitch accent categories in continuous speech. Our analytic approach also captures how language-specific knowledge and selective attention influences the neural processing of pitch accent categories.

Peroral endoscopic myotomy (POEM) is becoming the treatment of choice for achalasia. Data beyond 3 years are emerging but limited. We herein report our 10-year experience, focusing on long-term efficacy and safety including the prevalence, management, and sequelae of postoperative reflux.

This was a single-center prospective cohort study.

Six hundred ten consecutive patients received POEM from October 2009 to October 2019 for type I achalasia in 160 (26.2%), II in 307 (50.3%), III in 93 (15.6%), untyped achalasia in 25 (4.1%), and nonachalasia disorders in 23 (3.8%). Two hundred ninety-two (47.9%) patients had prior treatment(s). There was no aborted POEM. Median operation time was 54 minutes. Accidental mucosotomies occurred in 64 (10.5%) and clinically significant adverse events (csAEs) in 21 (3.4%) patients. There were no adverse events (AEs) leading to death, surgery, interventional radiology interventions/drains, or altered functional status. At a median follow-up of 30 months, 29 failures occurred, defined as postoperative Eckardt score >3 or need for additional treatment. The Kaplan-Meier clinical success estimates at year 1, 2, 3, 4, 5, 6, and 7 were 98%, 96%, 96%, 94%, 92%, 91%, and 91%, respectively. These are highly accurate estimates because only 13 (2%) patients were missing follow-up assessments. One hundred twenty-five (20.5%) patients had reflux symptoms more than once per week. At a median of 4 months, the pH study was completed in 406 (66.6%) patients and was positive in 232 (57.1%) and endoscopy in 438 (71.8%) patients and showed reflux esophagitis in 218 (49.8%), mostly mild.

POEM is exceptionally safe and highly effective on long-term follow-up, with >90% clinical success at ≥5 years.

90% clinical success at ≥5 years.

Nocardia farcinica is an opportunistic pathogen causing mainly pneumonia in immunocompromised patients, complicated in almost one-third of the cases by a thick-walled multiloculated cerebral abscess which induces significant morbidity and mortality. This review aims to assess the optimal treatment strategy for N.farcinica cerebral abscess.

Report of a case. Medline database was used to conduct a systematic review from inception to January 2020 looking for English-language articles focused on N.farcinica cerebral abscess, in accordance with the PRISMA guidelines.

The research yielded 54 articles for a total of 58 patients. N.farcinica cerebral abscess displayed three different neuroimaging patterns a single multiloculated abscess in half of the cases, multiple cerebral abscesses, or a small paraventricular abscess with meningitis. The patients who benefited from surgical excision of the abscess showed a trend towards a lower risk of surgical revision (8% versus 31%, P=0.06) and a lower mortality rate (8%an be preferred over needle aspiration. Long-term antibiotic therapy with cotrimoxazole is necessary thereafter.

The aim of this study was to describe progestin-associated meningiomas' characteristics, outcome and management.

We included 53 patients operated on and/or followed in the department for meningioma with progestin intake longer than one year and with recent drug discontinuation.

Cyproterone acetate (CPA), nomegestrol acetate (NomA), and chlormadinone acetate (ChlA) were involved in most cases. Mean duration of progestin drugs intake was 17.5 years. Tumors were multiple in 66% of cases and were located in the anterior and the medial skull base in 71% of cases. Transitional subtype represented 16/25 tumors; 19 meningiomas were WHO grade I and 6 were grade II. The rate of transitional subtype and skull base location was significantly higher compared to matched operated meningioma general population. No difference was observed given WHO classification. But Ki67 proliferation index tends to be lower and 5/6 of the WHO grade II meningiomas were classified as WHO grade II because of brain invasion. Angiogenesis chemical Strong progesterone receptors expression was observed in most cases.

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