Gut microbiome predicts cognitive function and depressive symptoms in late life.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Squamous Cell Carcinoma of Duodenum Secondary to Metastasis From Recurrent Head and Neck Cancer: A Case Report and Literature Review.

This report describes a case involving the diagnosis and treatment of squamous cell carcinoma (SCC) of the duodenum, which was found to be a metastatic lesion originating from recurrent head and neck cancer (HNC) in a 74-year-old female patient. The patient had a past medical history of gastroesophageal reflux disease (GERD), tonsillar SCC, and recurrent HNC. She presented with symptoms of burning, tingling, and numbness of the throat and left side of the tongue. Upon examination with an esophagogastroduodenoscopy, an ulcerated hard area mass was detected in the third portion of the duodenum. Biopsy results confirmed the mass to be a metastatic poorly differentiated SCC. The incidence of head and neck squamous cell carcinoma (HNSCC) metastasis to the duodenum is rare, likely due to the unique anatomic location and the lack of lymphatic drainage in the area. The patient was treated with a combination of paclitaxel, carboplatin, and pembrolizumab. This case underscores the significance of considering unusual sites of metastasis in HNSCC patients and utilizing advanced imaging modalities and immunotherapy to detect and treat these locations effectively.

Surgical repair of an unroofed coronary sinus in a dog.

A 5-year-old, 7.9 kg castrated male Miniature Dachsund presented with heart enlargement on radiography. The dog was asymptomatic. Echocardiography revealed a tubular structure running along the posterior wall of the left atrium and connecting to the right atrium on the caudal side of the left atrium and annulus, which was presumed to be a dilated coronary sinus. After confirming a shunt between the left atrium and coronary sinus by cardiovascular catheterization, an unroofed coronary sinus was diagnosed. Open-heart surgery using cardiopulmonary bypass was performed through left atriotomy. The defect between the left atrium and the coronary sinus was closed by suturing. The cardiac enlargement improved after surgery. The dog was still alive 1227 days after surgery without clinical signs.

Large Zenker's Diverticulum: A Case Report.

Zenker's diverticulum (ZD) is a type of esophageal diverticulum, a relatively rare disease in the pharyngoesophageal area. It is a pulsion diverticulum, or false diverticulum, located dorsally at the wall between the pharynx and esophagus. This area is known as Killian's triangle or dehiscence and is a region of relative weakness. Common symptoms of ZD include dysphagia, choking, persistent cough, loss of weight, hoarseness, halitosis, regurgitation of undigested food, and borborygmi within the cervical region. We are reporting a case of oropharyngeal dysphagia due to a ZD in a 65-year-old man with a history of worsening dysphagia for two years. Clinical presentation, diagnosis, and treatment options for ZD are discussed, along with the underlying pathophysiology of this condition.

Tunneled island pedicle flap reconstruction for upper lateral cutaneous lip defects.

BACKGROUND: Esthetic upper lateral cutaneous lip reconstruction preserves the apical triangle, nasolabial fold symmetry, and free margin position. The tunneled island pedicle flap (IPF) is a novel single-stage reconstruction to achieve these goals. OBJECTIVES: Describe the technique and patient and surgeon-reported outcomes for the tunneled IPF reconstruction of upper lateral cutaneous lip defects. METHODS: Retrospective chart review of consecutive tunneled IPF reconstruction following Mohs micrographic surgery (MMS) at a tertiary care center between 2014 and 2020. Patients rated their scars using the validated Patient Scar Assessment Scale (PSAS), and independent surgeons rated scars using the validated Observer Scar Assessment Scale (OSAS). Descriptive statistics were generated for patient demographics and tumor defect characteristics. RESULTS: Twenty upper lateral cutaneous lip defects were repaired with the tunneled IPF. Surgeons rated scars with a composite OSAS score of 11.83 ± 4.29 (mean, SD) [scale of 5 (normal skin) to 50 (worst scar imaginable)] and an overall scar score of 2.81 ± 1.11 [scale of 1 (normal skin) to 10 (worst scar imaginable)]. Patients rated their scars with a composite PSAS score of 10 ± 5.39 [scale of 6 (best possible score) to 60 (worst)] and with an overall score of 2.2 ± 1.78 [scale of 1 (normal skin) and 10 (very different from normal skin)]. One flap was surgically revised for pincushioning, but none experienced necrosis, hematoma, or infection. CONCLUSIONS: The tunneled IPF is a single-stage reconstruction for upper lateral cutaneous lip defects with favorable scar ratings by patients and observers.

Use of Rimegepant in the Management of Cervicogenic Headache Secondary to Trauma: A Case Series.

A cervicogenic headache (CH) originates from a cervical source. Multiple diagnostic criteria and treatment strategies for CH are present. Rimegepant is a calcitonin gene-related peptide receptor (CGRP) antagonist. We present a case series of three patients with CH who reported varying degrees of decreased headache intensity after using rimegepant.

Acute Mesenteric Ischemia Secondary to Superior Mesenteric Vein Thrombosis.

The thrombosis of the superior mesenteric vein (SMV) can result in ischemia of the intestine. A 71-year-old male presented with pain in the abdomen and a black tarry stool. The findings from computed tomography (CT) with the contrast of the abdomen suggest the thrombosis of the SMV. Heparin was administered, followed by thrombectomy and stenting of the SMV. The patient reported no complications and was shifted from heparin to apixaban and then discharged after a five-day hospital stay.

Acute Upper Extremity Ischemia Due to Cardioembolism From Undiagnosed Atrial Fibrillation.

The current study presents a case of right upper extremity ischemia secondary to cardioembolism in an elderly female with active and previously undiagnosed atrial fibrillation. The patient had no past medical history of any chronic cardiac disease or significant cardiac events. Computed tomographic angiography (CTA) was not performed due to her allergy to contrast material. A non-contrast computed tomography (CT) revealed mild atherosclerotic calcification of the right brachiocephalic artery; however, dissection or mural thrombus of the inflow vessels could not be ruled out. In evaluating a patient with acute ischemia of the upper limb, it is essential to obtain a complete history, including allergies, and be prepared to use alternative techniques for assessing arteries, if necessary. Routine cardiac function testing should also be prioritized in all elderly individuals, even those with no previous history of cardiovascular disease or symptoms.

The poly(A) polymerase beta gene may not be associated with azoospermia caused by Sertoli-cell-only syndrome in Japanese patients by comparing patients and normal controls.

Approximately 15% of couples are infertile, with half of these cases being due to a male factor. Testis-specific cytoplasmic poly(A) polymerase beta (PAPOLB) is known to be critical for spermatogenesis. In mice, the loss of function of the Papolb gene results in the arrest of spermiogenesis and in male infertility. To analyse the role of the PAPOLB gene in human male infertility, this study investigated the relevance of this gene to human Sertoli-cell-only syndrome (SCOS) with azoospermia. Mutation analysis of the PAPOLB coding region was performed on 139 Japanese patients by PCR and direct sequence analysis. No critical mutations directly causing SCOS were detected, but three single-nucleotide polymorphisms (SNPs; SNP1 (c1101C > T), SNP2 (c1347T > C) and SNP3 (c1903C > A)) were found in the coding region. However, there were no significant associations in the allelic and genotypic distributions of these three SNPs between the SCOS and control groups (p>.05). This study suggests a lack of association of PAPOLB with azoospermia due to SCOS in humans.

Lactococcus lactis KR-050L extract suppresses house dust mite induced-atopic skin inflammation through inhibition of keratinocyte and mast cell activation.

AIMS: Atopic dermatitis (AD) is a chronic inflammatory skin disease, with a steadily increasing prevalence. Lactic acid bacteria (LAB) have been widely used in the food industry and are an attractive option for preventing and treating allergic skin diseases. We previously isolated new LABs including Lactococcus lactis KR-050L from Gajuknamu kimchi, and showed the anti-inflammatory effects of extract of L. lactis KR-050L culture broth (LLK). In this study, we investigated the effects of LLK on AD. METHODS AND RESULTS: For the in vitro study, we used human keratinocytes (HaCaT) and mast cells (RBL-2H3). In vivo study, we investigated the effects of LLK on Dermatophagoides farinae extract (DFE) and 2,4-dinitrochlorobenzene (DNCB)-induced atopic skin inflammation in mice. LLK suppressed expression of pro-inflammatory cytokines and chemokines by down-regulation of p38 MAPK, STAT1 and nuclear translocation of NF-κB in keratinocytes. Topical application of LLK suppressed AD symptoms based on reduction in ear thickness, serum IgE levels and immune cell infiltration. Furthermore, LLK inhibited serum histamine levels and mast cells infiltration in vivo, and reduced mast cells activation in vitro. CONCLUSIONS: These results suggest that LLK inhibits AD symptoms through inhibition of keratinocytes and mast cells activation. SIGNIFICANCE AND IMPACT OF THE STUDY: LLK is a potential therapeutic candidate for AD treatment.

High-Frequency Ultrasound Imaging for Examination of Early Dental Caries.

The extent of dental tissue destruction during the treatment of white spot lesions (WSLs) increases with the severity of the lesion. If the depth and shape of WSLs can be predicted with a noninvasive diagnostic method before dental caries treatment, more conservative interventions can be planned. Given the superiority of high-frequency ultrasound (HFUS) imaging in observing the internal structures of the body, the present study aimed to verify the possibility of HFUS imaging to examine the depth and shape of WSLs. We prepared tooth samples and developed a biomicroscopic system with a HFUS transducer to obtain images of normal and WSL regions. HFUS images were compared with conventional ultrasound images and micro-computed tomography images. HFUS distinctly differentiated demineralization within WSL and normal regions. WSL depth calculated in the micro-computed tomography image was similar to that in HFUS. This study revealed that HFUS imaging has the potential to detect early dental caries and offer information on the invasion depth of early dental caries quantitatively.

The biological response to laser-aided direct metal-coated Titanium alloy (Ti6Al4V).

OBJECTIVES: Laser-engineered net shaping (LENS) of coated surfaces can overcome the limitations of conventional coating technologies. We compared the in vitro biological response with a titanium plasma spray (TPS)-coated titanium alloy (Ti6Al4V) surface with that of a Ti6Al4V surface coated with titanium using direct metal fabrication (DMF) with 3D printing technologies. METHODS: The in vitro ability of human osteoblasts to adhere to TPS-coated Ti6Al4V was compared with DMF-coating. Scanning electron microscopy (SEM) was used to assess the structure and morphology of the surfaces. Biological and morphological responses to human osteoblast cell lines were then examined by measuring cell proliferation, alkaline phosphatase activity, actin filaments, and RUNX2 gene expression. RESULTS: Morphological assessment of the cells after six hours of incubation using SEM showed that the TPS- and DMF-coated surfaces were largely covered with lamellipodia from the osteoblasts. Cell adhesion appeared similar in both groups. The differences in the rates of cell proliferation and alkaline phosphatase activities were not statistically significant. CONCLUSIONS: The DMF coating applied using metal 3D printing is similar to the TPS coating, which is the most common coating process used for bone ingrowth. The DMF method provided an acceptable surface structure and a viable biological surface. Moreover, this method is automatable and less complex than plasma spraying.Cite this article: T. Shin, D. Lim, Y. S. Kim, S. C. Kim, W. L. Jo, Y. W. Lim. The biological response to laser-aided direct metal-coated Titanium alloy (Ti6Al4V). Bone Joint Res 2018;7:357-361. DOI: 10.1302/2046-3758.75.BJR-2017-0222.R1.

Hypoplastic AI with Highly Variable Expressivity Caused by ENAM Mutations.

Tooth enamel, the hardest tissue in the human body, is formed after a complex series of interactions between dental epithelial tissue and the underlying ectomesenchyme. Nonsyndromic amelogenesis imperfecta (AI) is a rare genetic disorder affecting tooth enamel without other nonoral symptoms. In this study, we identified 2 novel ENAM mutations in 2 families with hypoplastic AI by whole exome sequencing. Family 1 had a heterozygous splicing donor site mutation in intron 4, NM_031889; c.123+2T>G. Affected individuals had hypoplastic enamel with or without the characteristic horizontal hypoplastic grooves in some teeth. Family 2 had a nonsense mutation in the last exon, c.1842C>G, p.(Tyr614*), that was predicted to truncate the protein by 500 amino acids. Participating individuals had at least 1 mutant allele, while the proband had a homozygous mutation. Most interestingly, the clinical phenotype of the individuals harboring the heterozygous mutation varied from a lack of penetrance to a mild hypoplastic enamel defect. We believe that these findings will broaden our understanding of the clinical phenotype of AI caused by ENAM mutations.

Dental implications in Hajdu-Cheney syndrome: A novel case report and review of the literature.

OBJECTIVE: To identify the molecular genetic etiology of an individual with a dysmorphic face, unusual teeth mobility, and root resorption. SUBJECTS AND METHODS: DNA samples were collected from a trio of family members, and whole-exome sequencing was performed. RESULTS: Mutational analysis revealed a de novo mutation (c.6787C>T) in the last exon of the NOTCH2 gene. This mutation would introduce a premature stop codon [p.(Gln2263*)] and generate a truncated protein without C-terminus, escaping from the nonsense-mediated decay system. Sanger sequencing confirmed that this mutation was generated spontaneously. CONCLUSIONS: In this study, we identified a novel nonsense mutation in the last exon of the NOTCH2 gene causing Hajdu-Cheney syndrome. We described the genotype and phenotype correlation and the related dental complications. These results will advance the understanding of the NOTCH2 signaling in periodontitis and root resorption.

Polyamine patterns in plasma of patients with systemic lupus erythematosus and fever.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations and serologic markers. In this study, we analyzed nine polyamine (PA) profiles of plasma from patients with SLE and healthy controls (HCs), and the relationship between the PA profiles and disease activity. PA alterations in plasma of 44 patients with SLE and fever were investigated using gas chromatography mass spectrometry (GC-MS) in selected ion monitoring mode using N-ethoxycarbonyl/ N-pentafluoropropionyl derivatives, and compared with those of 43 HCs. Patients with SLE and HCs showed differences in five of nine PA profiles. Among five changed PA levels, four PAs, namely N1-acetylcadaverine, spermidine, N1-acetylspermidine, and spermine, were dramatically decreased. However, the level of cadaverine was increased in patients with SLE. In the partial correlation with PA profiles and disease activity markers of SLE, several disease activity markers and nutritional markers were correlated with cadaverine, spermidine, and N 8-acetylspermidine. Thus, our results provide a comprehensive understanding of the relationship between PA metabolomics and disease activity markers in patients with SLE.

Evaluation of sulphur amino acid requirement of male Korean native ducklings from hatch to 21 day of age.

1. A dose-response experiment was conducted with male Korean native ducklings (KND) to evaluate the total sulphur amino acid (TSAA) requirement from hatch to 21 d of age. 2. A completely randomised design with 7 dietary TSAA concentrations (0.62%, 0.65%, 0.68%, 0.71%, 0.74%, 0.77% and 0.80%) were used with 6 replications per treatment. 3. Body weight (BW) and feed intake were measured weekly to calculate average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR). One duckling per pen (n = 6) was killed by cervical dislocation to weigh empty body and drumsticks at the conclusion of experiment. 4. BW was improved significantly with increasing TSAA content, in a non-linear manner. A significant decrease of FCR was shown with increasing TSAA contents. TSAA requirement was determined by taking a mean value after fitting the data to both a linear-plateau and a quadratic-plateau model. Estimated TSAA requirements were 0.70%, 0.70%, 0.66% and 0.70% for the maximum BW, ADG and ADFI and for the minimum FCR, respectively. Increasing TSAA content improved quantity of full body weight (FBW), empty body weight (EBW) and drumstick weight (DSW), but there was no effect on proportion of DSW in relation to EBW and proportion of EBW to FBW. 5. In conclusion, the growth of male KND during 1 to 21 d of age was improved with increasing TSAA content, suggesting optimal TSAA requirements estimated by two analysis models.

Exhaust ventilation in attached garages improves residential indoor air quality.

Previous research has shown that indoor benzene levels in homes with attached garages are higher than homes without attached garages. Exhaust ventilation in attached garages is one possible intervention to reduce these concentrations. To evaluate the effectiveness of this intervention, a randomized crossover study was conducted in 33 Ottawa homes in winter 2014. VOCs including benzene, toluene, ethylbenzene, and xylenes, nitrogen dioxide, carbon monoxide, and air exchange rates were measured over four 48-hour periods when a garage exhaust fan was turned on or off. A blower door test conducted in each garage was used to determine the required exhaust fan flow rate to provide a depressurization of 5 Pa in each garage relative to the home. When corrected for ambient concentrations, the fan decreased geometric mean indoor benzene concentrations from 1.04 to 0.40 µg/m3 , or by 62% (P<.05). The garage exhaust fan also significantly reduced outdoor-corrected geometric mean indoor concentrations of other pollutants, including toluene (53%), ethylbenzene (47%), m,p-xylene (45%), o-xylene (43%), and carbon monoxide (23%) (P<.05) while having no impact on the home air exchange rate. This study provides evidence that mechanical exhaust ventilation in attached garages can reduce indoor concentrations of pollutants originating from within attached garages.

Unexpected identification of a recurrent mutation in the DLX3 gene causing amelogenesis imperfecta.

OBJECTIVE: To identify the molecular genetic aetiology of a family with autosomal dominant amelogenesis imperfecta (AI). SUBJECTS AND METHODS: DNA samples were collected from a six-generation family, and the candidate gene approach was used to screen for the enamelin (ENAM) gene. Whole-exome sequencing and linkage analysis with SNP array data identified linked regions, and candidate gene screening was performed. RESULTS: Mutational analysis revealed a mutation (c.561_562delCT and p.Tyr188Glnfs*13) in the DLX3 gene. After finding a recurrent DLX3 mutation, the clinical phenotype of the family members was re-examined. The proband's mother had pulp elongation in the third molars. The proband had not hair phenotype, but her cousin had curly hair at birth. CONCLUSIONS: In this study, we identified a recurrent 2-bp deletional DLX3 mutation in a new family. The clinical phenotype was the mildest one associated with the DLX3 mutations. These results will advance the understanding of the functional role of DLX3 in developmental processes.

Can changing the timing of outdoor air intake reduce indoor concentrations of traffic-related pollutants in schools?

Traffic emissions have been associated with a wide range of adverse health effects. Many schools are situated close to major roads, and as children spend much of their day in school, methods to reduce traffic-related air pollutant concentrations in the school environment are warranted. One promising method to reduce pollutant concentrations in schools is to alter the timing of the ventilation so that high ventilation time periods do not correspond to rush hour traffic. Health Canada, in collaboration with the Ottawa-Carleton District School Board, tested the effect of this action by collecting traffic-related air pollution data from four schools in Ottawa, Canada, during October and November 2013. A baseline and intervention period was assessed in each school. There were statistically significant (P < 0.05) reductions in concentrations of most of the pollutants measured at the two late-start (9 AM start) schools, after adjusting for outdoor concentrations and the absolute indoor-outdoor temperature difference. The intervention at the early-start (8 AM start) schools did not have significant reductions in pollutant concentrations. Based on these findings, changing the timing of the ventilation may be a cost-effective mechanism of reducing traffic-related pollutants in late-start schools located near major roads.