Seasonal and mood independence of low basal prolactin secretion in premenopausal women with seasonal affective disorder

To test hypotheses of opposing roles of dopamine and serotonin in prolactin secretion in seasonal affective disorder, the authors determined basal serum prolactin concentrations for premenopausal women, eight with and 14 without seasonal affective disorder, in late afternoon during the follicular phase of the menstrual cycle (and a subgroup during the luteal phase) in winter and summer. Despite their significantly higher Hamilton depression scale scores in winter than in summer, the patients had significantly lower prolactin concentrations than the control subjects in both seasons. These results suggest that low prolactin secretion may be a trait characteristic in seasonal affective disorder.     

Misinterpretation of glioblastoma as ADEM: potentially harmful consequences of over-diagnosis of COVID-19 vaccine-associated adverse events

Journal of Neurology -     

Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome

The Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with uni- or bilateral coronal synostosis and mild limb deformities. It is caused by loss-of-function mutations of the TWIST 1 gene. In an attempt to delineate functional features separating SCS from Muenke's syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3. Within a total of 124 independent pedigrees, 39 (71 patients) were identified to carry 25 different mutations of TWIST 1 including 14 novel mutations, to which six whole gene deletions were added. The 71 patients were compared with 42 subjects from 24 pedigrees carrying the Pro250Arg mutation in FGFR3 and 65 subjects from 61 pedigrees without a detectable mutation. Classical SCS associated with a TWIST 1 mutation could be separated phenotypically from the Muenke phenotype on the basis of the following features: low-set frontal hairline, gross ptosis of eyelids, subnormal ear length, dilated parietal foramina, interdigital webbing, and hallux valgus or broad great toe with bifid distal phalanx. Functional differences were even more important: intracranial hypertension as a consequence of early progressive multisutural fusion was a significant problem in SCS only, while mental delay and sensorineural hearing loss were associated with the Muenke's syndrome. Contrary to previous reports, SCS patients with complete loss of one TWIST allele showed normal mental development.     

Characterizing the Followers and Tweets of a Marijuana-Focused Twitter Handle

Background

Twitter is a popular social media forum for sharing personal experiences, interests, and opinions. An improved understanding of the discourse on Twitter that encourages marijuana use can be helpful for tailoring and targeting online and offline prevention messages.

Objectives

The intent of the study was to assess the content of “tweets” and the demographics of followers of a popular pro-marijuana Twitter handle (@stillblazingtho).

Methods

We assessed the sentiment and content of tweets (sent from May 1 to December 31, 2013), as well as the demographics of consumers that follow a popular pro-marijuana Twitter handle (approximately 1,000,000 followers) using Twitter analytics from Demographics Pro. This analytics company estimates demographic characteristics based on Twitter behavior/usage, relying on multiple data signals from networks, consumption, and language and requires confidence of 95% or above to make an estimate of a single demographic characteristic.

Results

A total of 2590 tweets were sent from @stillblazingtho during the 8-month period and 305 (11.78%) replies to another Twitter user were excluded for qualitative analysis. Of the remaining 2285 tweets, 1875 (82.06%) were positive about marijuana, 403 (17.64%) were neutral, and 7 (0.31%) appeared negative about marijuana. Approximately 1101 (58.72%) of the positive marijuana tweets were perceived as jokes or humorous, 340 (18.13%) implied that marijuana helps you to feel good or relax, 294 (15.68%) mentioned routine, frequent, or heavy use, 193 (10.29%) mentioned blunts, marijuana edibles, or paraphernalia (eg, bongs, vaporizers), and 186 (9.92%) mentioned other risky health behaviors (eg, tobacco, alcohol, other drugs, sex). The majority (699,103/959,143; 72.89%) of @stillblazingtho followers were 19 years old or younger. Among people ages 17 to 19 years, @stillblazingtho was in the top 10% of all Twitter handles followed. More followers of @stillblazingtho in the United States were African American (323,107/759,407; 42.55%) or Hispanic (90,732/759,407; 11.95%) than the Twitter median average (African American 22.4%, inter-quartile ratio [IQR] 5.1-62.5%; Hispanic 5.4%, IQR 3.0-10.8%) and among Hispanics, @stillblazingtho was in the top 30% of all Twitter handles followed.

Conclusions

Young people are especially responsive to social media influences and often establish substance use patterns during this phase of development. Our findings underscore the need for surveillance efforts to monitor the pro-marijuana content reaching young people on Twitter.     

Long term follow up of through-the-scope balloon dilation as compared to strictureplasty and bowel resection of intestinal strictures in crohn’s disease

Background & aims: Ileo-colonic strictures are common complication of Crohn’s disease (CD), and may result in repeated endoscopic or surgical therapy with a risk of further complications, such as perforation or short bowel syndrome. Strictures develop as a consequence of tissue remodelling and fibrosis due to chronic inflammation. This study compares the outcome of CD patients undergoing primarily endoscopic treatment with those undergoing surgery at an university hospital. Methods: In this study we retrospectively included 88 CD patients with intestinal strictures (37 males, 51 females, mean age 40 years, range 19-65 years) of both our medical and our surgical department, who underwent either surgical or endoscopic therapy between January 2002 and January 2006 with prospective, controlled follow-up, extended till January 2010 (mean follow-up period: 5 years; range 4-8 years). The primary end-point was operation- and symptom-free time. Patients were primarily divided into four groups: only surgical therapy, only endoscopic therapy, endoscopy with subsequent surgery, and initial surgical therapy followed by endoscopic dilations. Results: 53% of all patients remained surgery-free with mean follow-up of 49 months; a single endoscopic dilation was sufficient enough in 9 patients to achieve a surgery-free time of 51 months, other patients required up to 5 dilations. The average interval between first and second dilation was 6.5 months, between second and third 10.5 months. In the group of patients with only endoscopic therapy, surgery- and symptom-free time was shorter, as compared to the group of only surgical therapy. We found that stenoses in the surgical group with an average length of 6.5 cm were as expected longer, as compared to the endoscopic group (3 cm, ranging from 2-4 cm). The surgery-free time was 49 months (42-71 months, P = 0.723) with a symptom-free time of 12 months (4.5-46 months, P = 0.921). In the group of only surgically treated patients, 68.4% of the patients had only one stenosis, 18.4% had 2-3 stenoses and 13.2% more than 3 stenoses. In all patients the surgery- and symptoms- free time was 69 months (57-83 months, P = 0.850 and 0.908). The other two groups showed similar results. We found no significant effect of characteristic of stenosis (length, inflammation, the number of stenoses), injection of prednisolone, disease activity at the time of dilation and medication at the time of dilation on the long-term outcome. Importantly, the success of symptom free time correlated with the diameter of the balloon. Conclusions: Endoscopic dilation should be considered as a first-line therapy for short, accessible, fibrotic strictures. Careful patient selection and proper diagnostic imaging pre-procedure are essential requirements for safe and successful treatment. The balloon diameter seems to correlate positively with the long term outcome of dilation. However, at ever shorter intervals between endoscopic interventions, surgery should be discussed as an option for further treatment.     

The immunogenicity and efficacy against H5N1 challenge of reverse genetics-derived H5N3 influenza vaccine in ducks and chickens

H5N1 avian influenza viruses are continuing to spread in waterfowl in Eurasia and to threaten the health of avian and mammalian species. The possibility that highly pathogenic (HP) H5N1 avian influenza is now endemic in both domestic and migratory birds in Eurasia makes it unlikely that culling alone will control H5N1 influenza. Because ducks are not uniformly killed by HP H5N1 viruses, they are considered a major contributor to virus spread. Here, we describe a reverse genetics-derived high-growth H5N3 strain containing the modified H5 of A/chicken/Vietnam/C58/04, the N3 of A/duck/Germany/1215/73, and the internal genes of A/PR/8/34. One or two doses of inactivated oil emulsion vaccine containing 0.015 to 1.2 microg of HA protein provide highly efficacious protection against lethal H5N1 challenge in ducks; only the two dose regimen has so far been tested in chickens with high protective efficacy.     

Reassortment and interspecies transmission of North American H6N2 influenza viruses

To identify the protein encoded by a 687-bp open reading frame (ORF) of a salI genomic DNA fragment of shrimp white spot syndrome virus (WSSV), we expressed the ORF in a baculovirus/insect cell expression system. The apparent molecular mass of the recombinant protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was 35 kDa in insect cells. Antibody raised against bacterially synthesized protein of the ORF identified a nucleocapsid protein (VP35) in the extracts of both the purified WSSV virions and the nucleocapsids which comigrated with the 35-kDa baculovirus-expressed recombinant protein on SDS-PAGE. We also show by transient expression in insect cells (Sf9) that VP35 targets the nucleus. Two potential nuclear localization signals (NLSs) were characterized, but only one of them was important for targeting VP35 to the nuclei of transfected insect cells. Replacement of a cluster of four positively charged residues ((24)KRKR(27)) at the N terminus of the protein with AAAA resulted in mutant proteins that were distributed only in the cytoplasm, thus confirming that this sequence is a critical part of the functionally active NLS of VP35.     

Characterization of lymphoid follicles with red ring signs as first manifestation of early Crohn's disease by conventional histopathology and confocal laser endomicroscopy

Background and aims

Clinical observations suggest that the lymphoid follicles (LFs) may play a crucial role in the pathogenesis of inflammatory bowel disease (IBD), especially in Crohn’s disease (CD) as the site of initial mucosal inflammation. The aim of this study was to compare the morphology of LFs in CD, ulcerative colitis (UC) and control patients using confocal laser endomicroscopy (CLE) in correlation to histological and immunohistochemical findings of biopsies.

Methods

79 patients with IBD (46 with CD, 32 with UC and 1 patient with indeterminate colitis) and 67 controls patients were enrolled prospectively in this study. Median age was 32.5 years (range 19-65) and 37.4 years (range 20-65 years) respectively. To analyze the LFs, standardized images from the terminal ileum and the colon were taken using white-light video endoscopes. Additionally, CLE was performed to analyze subsurface structure of LFs. Targeted biopsies of LFs were analyzed using haematoxylin and eosin stain and immunohistochemistry.

Results

LFs were seen in all parts of the lower GI tract, but mostly in the terminal ileum and cecum. Endoscopy in 15 out of 17 patients with the first manifestation of CD showed LFs surrounded by red ring (so-called red ring sign, RRS). Histologically, LFs with RRS showed hypervascularization at the base of the LFs associated with numerous CD15-positive granulocytes. Similar features were not seen in LFs without RRS and in the control group. In some LFs with RRS early aphthous ulcers were seen. Using CLE, RRS showed abolished normal crypt architecture, crypt distortion, increased cellular infiltrate within the lamina propria, and dilated vessels.

Conclusion

LFs with RRS probably represent an early sign of aphthous ulcers in early CD and, thus, may be considered as early markers of first manifestation and flares in CD.     

Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation

Overproduction of cytokines by T helper 2 (Th2) cells in the lung is thought to be a cause of asthma. Here we report that innate lymphocytes termed lung natural helper (LNH) cells are a T cell-independent source of Th2 cell-type cytokines in protease allergen-treated lungs. LNH (Lin(-)Sca-1(+)c-kit(+/lo)CD25(+)CD127(+)) cells, when stimulated by IL-33 plus IL-2, IL-7, or thymic stroma lymphopoietin (TSLP), produced large amounts of IL-5 and IL-13. Intranasal administration of protease allergen papain induced eosinophil infiltration and mucus hyperproduction in the lung of wild-type and Rag1(-/-) mice, but not in Rag2(-/-)Il2rg(-/-) mice that lack LNH cells. LNH cell depletion inhibited papain-induced airway inflammation in Rag1(-/-) mice whereas adoptive transfer of LNH cells enabled Rag2(-/-)Il2rg(-/-) mice to respond to papain. Treatment of lung explants with papain induced IL-33 and TSLP production by stroma cells and IL-5 and IL-13 production by LNH cells. Thus, LNH cells are critical for protease allergen-induced airway inflammation.     

Characterization of a recombinant canine coronavirus with a distinct receptor-binding (S1) domain

Canine alphacoronaviruses (CCoV) exist in two serotypes, type I and II, both of which can cause severe gastroenteritis. Here, we characterize a canine alphacoronavirus, designated CCoV-A76, first isolated in 1976. Serological studies show that CCoV-A76 is distinct from other CCoVs, such as the prototype CCoV-1-71. Efficient replication of CCoV-A76 is restricted to canine cell lines, in contrast to the prototypical type II strain CCoV-1-71 that more efficiently replicates in feline cells. CCoV-A76 can use canine aminopeptidase N (cAPN) receptor for infection of cells, but was unable to use feline APN (fAPN). In contrast, CCoV-1-71 can utilize both. Genomic analysis shows that CCoV-A76 possesses a distinct spike, which is the result of a recombination between type I and type II CCoV, that occurred between the N- and C-terminal domains (NTD and C-domain) of the S1 subunit. These data suggest that CCoV-A76 represents a recombinant coronavirus form, with distinct host cell tropism.