Autistic adults benefit from and enjoy learning via social interaction as much as neurotypical adults do.

BACKGROUND: Autistic people show poor processing of social signals (i.e. about the social world). But how do they learn via social interaction? METHODS: 68 neurotypical adults and 60 autistic adults learned about obscure items (e.g. exotic animals) over Zoom (i) in a live video-call with the teacher, (ii) from a recorded learner-teacher interaction video and (iii) from a recorded teacher-alone video. Data were analysed via analysis of variance and multi-level regression models. RESULTS: Live teaching provided the most optimal learning condition, with no difference between groups. Enjoyment was the strongest predictor of learning: both groups enjoyed the live interaction significantly more than other condition and reported similar anxiety levels across conditions. LIMITATIONS: Some of the autistic participants were self-diagnosed-however, further analysis where these participants were excluded showed the same results. Recruiting participants over online platforms may have introduced bias in our sample. Future work should investigate learning in social contexts via diverse sources (e.g. schools). CONCLUSIONS: These findings advocate for a distinction between learning about the social versus learning via the social: cognitive models of autism should be revisited to consider social interaction not just as a puzzle to decode but rather a medium through which people, including neuro-diverse groups, learn about the world around them. Trial registration Part of this work has been pre-registered before data collection https://doi.org/10.17605/OSF.IO/5PGA3.

Loss of Flot2 expression in deep cerebellar nuclei neurons of mice with Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is caused by a deficiency of the NPC1 or NPC2 gene, leading to storages of unesterified cholesterol and sphingolipids. Cerebellar ataxia is a main symptom of NPC and the deep cerebellar nuclei (DCN) is the sole signal output of the cerebellum. In this study, we explored the pathological changes in DCN neurons of Npc1 knockout mice (Npc1-). We first demonstrated that DCN neurons of Npc1- mice had prominent ganglioside GM2 accumulation in the late endosomes but not in the lysosomes. More importantly, Flot2 expression, a marker for the lipid rafts, was lost. Single-nucleus RNA sequencing analysis revealed a generalized reduction in gene expression in DCN neurons, though Camk1d, encoding one of the Ca2+/calmodulin-dependent protein kinases (CaMKs), increased in expression. We treated Npc1- mice with CaMK inhibitor KN-93, but CaMK1D expression increased further. We also fed Npc1- mice with two medications for NPC. We found that miglustat, a sphingolipid synthesis inhibitor, increased the expression of Flot2. Moreover, N-acetyl l-leucine (NALL), an experimental medicine for NPC, recovered Flot2 expression. Therefore, our data suggest that in Npc1- mice, GM2 sequestration and the loss of lipid rafts lead to cell dysfunction and symptoms of NPC.

Research on the Rescue Time of the Taiwan Marathon Emergency Medical Service System Between 2013 and 2021.

BACKGROUND: While there are several studies on marathon injuries worldwide, there are no related studies on the Taipei Marathon regarding the rescue time of onsite injury cases, the incidence of out-of-hospital cardiac arrest (OHCA) cases, and the success rate of recovery of spontaneous circulation (ROSC). This study aims to fill that gap. HYPOTHESIS: The rescue time onsite of contact injury cases was in the prime time for lifesaving. STUDY DESIGN: Descriptive epidemiological study. LEVEL OF EVIDENCE: Level 2c. METHODS: This is a retrospective study of numerical and timeflow data using descriptive statistics. Our data were obtained from records of the Taipei Marathon from 2013 to 2021. These included (1) notification data, (2) the time record of the emergency care personnel in contact with patients, (3) incidence of OHCA, (4) the success rate of ROSC, (5) the location of occurrence of OHCA, and (6) emergency medical service capacity and configuration. RESULTS: The average time taken for first contact was 1.56 minutes in OHCA cases, and the total incidence rate of OHCA in 9 years was 4 people per 100,000 people, with a 100% ROSC success rate. Further, the location of OHCA cases was mostly in Q4 of the race (66.67%), followed by Q3 (22.22%) and Q2 (1.11%). The average number of emergency care personnel per marathon was 78, spread across 6 rescue and 6 medical stations and equipped with 8 ambulances and 35 automated external defibrillators. CONCLUSION: Shortening the arrival time of medical personnel to the scene and implementing a complete chain of survival can improve survival rates. Other ways to provide faster and more timely emergency rescue services require further study. CLINICAL RELEVANCE: Contact with patients as soon as possible, timely implementation of cardiopulmonary resuscitation, and use of an automated external defibrillator are the basic requirements of the chain of survival theory.

Relationships among phthalate exposure, oxidative stress, and insulin resistance in young military soldiers: A cumulative risk assessment and mediation approach.

BACKGROUND: Epidemiological studies concerning whether oxidative stress mediates phthalate exposure-insulin resistance (IR) associations in young adults are limited. Therefore, we investigated this potential mediation by using a cumulative risk approach involving daily intake (DI) and a hazard index (HIRfD). METHODS: The participants were 391 Taiwanese military personnel. This study measured their IR (as homeostatic model assessment of estimated IR [HOMA-IR]), levels of oxidative stress biomarkers (8-hydroxy-2-deoxyguanosine, 8-nitroguanine, 8-iso-prostaglandin F2α, and N-acetyl-S-[tetrahydro-5-hydroxy-2-pentyl-3-furanyl]-L-cysteine [HNE-MA]), the sum of these four biomarkers (ΣOS), and urinary phthalate metabolite concentrations. The HIRfD was estimated on the basis of urinary levels of phthalate metabolite, and the DI of five phthalates was determined: dimethyl phthalate, benzyl butyl phthalate (BBzP), diethyl phthalate, dibutyl phthalate (DBP), and di (2-ethylhexyl) phthalate (DEHP). Logistic regression models were employed to explore associations among DI, HIRfD, oxidative stress biomarkers, and HOMA-IR values. The role played by oxidative stress in the phthalate exposure-HOMA-IR association was determined using mediation analysis. RESULTS: We discovered positive associations between high DI of DBP, BBzP, and DEHP; high HIRfD; and high ΣOS. High ΣOS and HNE-MA were associated with a higher likelihood of a high HOMA-IR value. Mediation analysis indicated that high ΣOS and HNE-MA were significant mediators of the associations between phthalates and IR. CONCLUSION: Oxidative stress may partially mediate the phthalate-IR relationship in young adults.

Hepatitis C Virus NS3 Protein Plays a Dual Role in WRN-Mediated Repair of Nonhomologous End Joining.

Hepatitis C virus (HCV) NS3 protein possesses protease and helicase activities and is considered an oncoprotein in virus-derived hepatocellular carcinoma. The NS3-associated oncogenesis has been studied but not fully understood. In this study, we have identified novel interactions of the NS3 protein with DNA repair factors, Werner syndrome protein (WRN) and Ku70, in both an HCV subgenomic replicon system and Huh7 cells expressing NS3. HCV NS3 protein inhibits WRN-mediated DNA repair and reduces the repair efficiency of nonhomologous end joining. It interferes with Ku70 recruitment to the double-strand break sites and alters the nuclear distribution of WRN-Ku repair complex. In addition, WRN is a substrate of the NS3/4A protease; the level of WRN protein is regulated by both the proteasome degradation pathway and HCV NS3/4A protease activity. The dual role of HCV NS3 and NS3/4A proteins in regulating the function and expression level of the WRN protein intensifies the effect of impairment on DNA repair. This may lead to an accumulation of DNA mutations and genome instability and, eventually, tumor development.IMPORTANCE HCV infection is a worldwide problem of public health and a major contributor to hepatocellular carcinoma. The single-stranded RNA virus with RNA-dependent RNA polymerase experiences a high error rate and develops strategies to escape the immune system and hepatocarcinogenesis. Studies have revealed the involvement of HCV proteins in the impairment of DNA repair. The present study aimed to further elucidate mechanisms by which the viral NS3 protein impairs the repair of DNA damage. Our results clearly indicate that HCV NS3/4A protease targets WRN for degradation, and, at the same time, diminishes the repair efficiency of nonhomologous end joining by interfering with the recruitment of Ku protein to the DNA double-strand break sites. The study describes a novel mechanism by which the NS3 protein influences DNA repair and provides new insight into the molecular mechanism of HCV pathogenesis.

Retinotomy and silicone oil for detachments complicated by anterior inferior proliferative vitreoretinopathy.

AIM: To describe a subset of patients with recurrent retinal detachments caused by anterior intraretinal and subretinal proliferative vitreoretinopathy (PVR), which required greater than 180 degrees retinotomy and silicone oil tamponade. METHODS: Interventional case series. Forty-one patients underwent >180 degrees retinotomy, anterior retinectomy, removal of subretinal membranes, laser to the retinotomy edge and silicone oil tamponade. Risk factors for detachment, prior surgical history and PVR location were examined. Main outcomes included change in visual acuity, recurrent detachment and postoperative complications. RESULTS: Cataract extraction (49%), high myopia (29%) and lattice degeneration (27%) were preoperative risk factors. The average number of prior procedures for retinal attachment was 2.3 (SD 0.9). The majority of detachments were inferior and related to anterior intraretinal and subretinal PVR. Twenty-four patients (59%) saw 20/200 or better. Eleven patients (27%) had poor vision (<20/400) at the end of follow-up. Thirty-seven retinas (90%) remained attached. Increased rates of postoperative corneal decompensation (p<0.0001) and silicone oil in the anterior chamber (p<0.0001) were statistically significant markers of poor visual outcome. CONCLUSIONS: Patients with complex PVR requiring a large retinotomy often had similar presurgical conditions. A large inferior retinotomy effectively addressed proliferations where they most frequently occur, and silicone oil was beneficial.

Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies.

Natural killer (NK)-cell malignancies are among the most aggressive lymphoid neoplasms with very poor prognosis. We performed array comparative genomic hybridization analysis on a number of NK cell lines and primary tumors to gain better understanding of the pathogenesis and tumor biology of these malignancies. We also obtained transcriptional profiles of genes residing in these regions and compared them with normal and activated NK cells. Only 30-50% of the genes residing in the gained or deleted regions showed corresponding increased or decreased expression. However, many of the upregulated genes in regions of gain are functionally important for the proliferation and growth of the neoplastic population. Genes downregulated in regions of loss included many transcription factors or repressors, tumor suppressors or negative regulators of the cell cycle. The minimal common region of deletion in 6q21 included three known genes (PRDM1, ATG5 and AIM1) showing generally low expression. Mutations resulting in truncated PRDM1 and changes in conserved amino-acid sequences of AIM1 were detected. Highly methylated CpG islands 5' of PRDM1 and AIM1 correlated with low expression of the transcripts. Reversal of methylation by Decitabine induced expression of PRDM1 and cell death. In conclusion, we have shown a general tumor-promoting effect of genetic alterations and have identified PRDM1 as the most likely target gene in del6q21. ATG5, an essential gene for autophagy and AIM1, a gene implicated in melanoma, may also participate in the functional abnormalities.

Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress.

Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the antioxidant catalase within certain cells might protect neighboring cells. To test this hypothesis, we transduced retinal pigment epithelial (RPE) cells in vitro and in vivo with adenovirus carrying the catalase gene (Ad.CMV.catalase). After transduction of only a subset of RPE cells in vitro, all cells in the culture were protected from exogenous hydrogen peroxide. Similarly, in vivo, eyes injected with Ad. CMV. catalase had high catalase levels in the RPE, which protected the adjacent photoreceptors from light damage and reduced photoreceptor oxidative stress as measured by the markers 4-hydroxynonenal and nitrotyrosine. Both in vitro and in vivo, gene therapy with Ad. CMV. catalase protected neighboring cells from oxidative stress-induced terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) positivity. The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells.

Perception of aspiration and place of articulation of Cantonese initial stops by normal and sensorineural hearing-impaired listeners.

This study investigated the use of acoustic cues to the perception of aspiration and place of articulation of Cantonese initial stops by bilateral severely hearing-impaired (n = 14) and normal-hearing (n = 14) adolescents. The stimuli were consonant-vowel (CV) words spoken by two male speakers in which the initial consonants /ph, p, th, t, kh, k/ were followed by the diphthong /[symbol: see text]i/. Subjects listened to the stimuli through a loudspeaker and chose the correct initial consonant among six choices. Three test conditions (short, medium and long voice onset time, or VOT) were prepared by increasing the VOT of unaspirated stops and by decreasing the VOT of aspirated stops. The results showed that the presence of aspiration noise was an important cue for normal listeners in the perception of aspiration, but not for hearing-impaired listeners. Hearing-impaired listeners used formant transitions as the main cue to the perception of aspiration. VOT was a weak aspiration cue for both groups. In the perception of place of articulation, normal listeners appeared to rely mainly on formant transitions and release burst information rather than VOT. The recognition of place by hearing-impaired listeners was at chance level for all the experimental stimuli, showing that these listeners were unable to use VOT, formant transitions or release burst information as cues to place.

Salmonella enterica serovar typhi uses type IVB pili to enter human intestinal epithelial cells.

DNA sequencing upstream of the Salmonella enterica serovar Typhi pilV and rci genes previously identified in the ca. 118-kb major pathogenicity island (X.-L. Zhang, C. Morris, and J. Hackett, Gene 202:139-146, 1997) identified a further 10 pil genes apparently forming a pil operon. The product of the pilS gene, prePilS protein (a putative type IVB structural prepilin) was purified, and an anti-prePilS antiserum was raised in mice. Mutants of serovar Typhi either lacking the whole pil operon or with an insertion mutation in the pilS gene were constructed, as was a strain in which the pilN to pilV genes were driven by the tac promoter. The pil(+) strains synthesized type IVB pili, as judged by (i) visualization in the electron microscope of thin pili in culture supernatants of one such strain and (ii) the presence of PilS protein (smaller than the prePilS protein by removal of the leader peptide) on immunoblotting of material pelleted by high-speed centrifugation of either the culture supernatant or sonicates of pil(+) strains. Control pil mutants did not express the PilS protein. A pilS mutant of serovar Typhi entered human intestinal INT407 cells in culture to levels only 5 to 25% of those of the wild-type strain, and serovar Typhi entry was strongly inhibited by soluble prePilS protein (50% inhibition of entry at 1.4 microM prePilS).

Rapid determination of total cholesterol in homogenized milk.

A rapid method that is amenable to automation has been developed for the determination of total cholesterol in homogenized milk. The milk sample is saponified in ethanolic KOH in the presence of an internal standard, cholestane. Cholesterol and the internal standard are then isolated by solid-phase extraction on a nonpolar adsorbent and eluted with organic solvent. The evaporated extract is derivatized and analyzed by capillary gas chromatography. Average recovery of cholesterol acetate added to milk prior to saponification was 95%. The average relative standard deviation for repeated analyses was 2%. The limit of detection for this method is 2 mg/100 g. Twenty samples can be analyzed by one analyst in a normal work day if the gas chromatograph is equipped with an autosampler. This method has been compared with a modified AOAC method for the determination of total cholesterol. At a confidence level of 95%, no difference was observed between the 2 methods.