A SEER analysis of survival and prognostic factors in merkel cell carcinoma of the head and neck region.

While Merkel cell carcinoma (MCC) of the head and neck is highly malignant, it remains poorly characterized due to its rarity. The purpose of this study was to examine prognostic factors for overall survival (OS) and disease-specific survival (DSS) in patients with MCC of the head and neck region. The Surveillance, Epidemiology and End Results registry was reviewed for patients diagnosed between 1984 and 2016 with histologically confirmed, primary MCC of the head and neck region. A total of 2818 patients met the inclusion criteria, with a median age at diagnosis of 77 years. At five and 10 years, respectively, the OS was 42.4% and 25.1% and the DSS was 67.9% and 64.1%. Multivariate Cox analysis indicated that predictors of decreased DSS included age at diagnosis ≥75 years, white race, increasing tumor spread, lymph node involvement and either the lip or the scalp/neck as a primary site. When adjusting for the aforementioned factors, tumor depth was not found to be a prognostic factor for DSS. We anticipate these results will help clinicians to counsel patients regarding expectations and potential prognosis.

Resting-State Functional MRI for Determining Language Lateralization in Children with Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: Task-based fMRI is a noninvasive method of determining language dominance; however, not all children can complete language tasks due to age, cognitive/intellectual, or language barriers. Task-free approaches such as resting-state fMRI offer an alternative method. This study evaluated resting-state fMRI for predicting language laterality in children with drug-resistant epilepsy. MATERIALS AND METHODS: A retrospective review of 43 children with drug-resistant epilepsy who had undergone resting-state fMRI and task-based fMRI during presurgical evaluation was conducted. Independent component analysis of resting-state fMRI was used to identify language networks by comparing the independent components with a language network template. Concordance rates in language laterality between resting-state fMRI and each of the 4 task-based fMRI language paradigms (auditory description decision, auditory category, verbal fluency, and silent word generation tasks) were calculated. RESULTS: Concordance ranged from 0.64 (95% CI, 0.48-0.65) to 0.73 (95% CI, 0.58-0.87), depending on the language paradigm, with the highest concordance found for the auditory description decision task. Most (78%-83%) patients identified as left-lateralized on task-based fMRI were correctly classified as left-lateralized on resting-state fMRI. No patients classified as right-lateralized or bilateral on task-based fMRI were correctly classified by resting-state fMRI. CONCLUSIONS: While resting-state fMRI correctly classified most patients who had typical (left) language dominance, its ability to correctly classify patients with atypical (right or bilateral) language dominance was poor. Further study is required before resting-state fMRI can be used clinically for language mapping in the context of epilepsy surgery evaluation in children with drug-resistant epilepsy.

Correction to: Cesarean delivery to prevent anal incontinence: a systematic review and meta-analysis.

The original article can be found online.

Cesarean delivery to prevent anal incontinence: a systematic review and meta-analysis.

BACKGROUND: Cesarean delivery (CD), is increasingly recommended as a mode of delivery that prevents the anal incontinence (AI) that arises in some women after vaginal delivery (VD). The assessment of the efficacy of CD in this regard was the subject of this systematic review. METHODS: Searches were conducted in Medline, EMBASE and the Cochrane Library. Both randomized (RCTs) and non-randomized trials (NRTs) comparing the risk of sustained fecal and/or flatus incontinence after VD or CD were sought from 1966 to 1 January, 2019. Studies were eligible if they assessed AI more than 6 months after birth, and had statistical adjustment for at least one of the three major confounders for AI: age, maternal weight or parity. In addition, each study was required to contain more than 250 participants, more than 50 CDs and more than 25 cases of AI. Data after screening and selection were abstracted and entered into Revman for meta-analysis. Analyses were done for combined fecal and flatus incontinence (comAI), fecal incontinence (FI), gas incontinence (GI), CD before or during labor, time trend of incontinence after delivery, assessment of both statistical and clinical heterogeneity, parity and late incident AI. RESULTS: Out of the 2526 titles and abstracts found, 24 eligible studies were analyzed, 23 NRTs and one RCT. These included women with 29,597 VDs and women with 6821 CDs. Among the primary outcomes, VD was found not to be a significant predictor of postpartum comAI compared to CD in 6 studies, incorporating 18,951 deliveries (OR = 0.74; 0.54-1.02). VD was also not a significant predictor of FI in 14 studies, incorporating 29,367 deliveries, (OR = 0.89; 0.76-1.05). VD was not a significant predictor of GI in six studies, incorporating 6724 deliveries (OR = 0.96; 0.79-1.18). The strength of the grading of recommendations, assessment, development and evaluations (GRADE) evidence for each of these was low for comAI and moderate for FI and GI (upgrade for lack of expected effect). Time trend FI showed incontinence at 3 months often resolved at 1 year. Other secondary analyses assessing parity, delayed incidence of FI, clinical and statistical heterogeneity, spontaneous VD only, late risk of incidence of AI, and CD in or prior to labor all had similar results as in the primary outcomes. CONCLUSIONS: There are three components of pelvic floor dysfunction that are thought to be caused by VD and hopefully prevented by CD: AI, urinary incontinence and pelvic floor prolapse. Of these, AI was not found to be reliably prevented by CD in this review.

Decreased maternal behavior and anxiety in ephrin-A5-/- mice.

During development of the nervous system, molecular signals mediating cell-cell interactions play critical roles in the guidance of axonal growth and establishment of synaptic functions. The Eph family of tyrosine kinase receptors and their ephrin ligands has been shown to mediate neuronal interactions in the development of topographic axon projection maps in several brain regions, and the loss of Eph activities result in defects in select axonal pathways. However, effects of deficiencies of the Eph signals on animal behavior have not been well documented. In this study, we showed that inactivation of a ligand of the Eph receptors, ephrin-A5, resulted in defects in maternal behavior and alterations in anxiety. Female ephrin-A5 -/- mice show significant defects in nest building and pup retrieval. In addition, lower levels of anxiety were observed in both male and female null mice. These changes were not due to deficiencies in estradiol, progesterone or corticosterone levels. Our observations suggest that ephrin-A5 plays a key role in the development and/or function of neural pathways mediating mouse maternal care and anxiety.

Elevating glucose and insulin secretion by carbohydrate formulation diets in late lactation to improve post-weaning fertility in primiparous sows.

Primiparous (P1) sows commonly lose excessive body reserves to meet energy requirements for maintenance and milk production during lactation, and consequently, post-weaning reproductive performance may be compromised. The present studies determined whether ad libitum feeding a glucogenic carbohydrate diet (CHO) during late lactation could stimulate insulin and glucose secretion (experiment 1) and improve subsequent litter size (experiment 2). For experiment 1, 15 P1 sows, and for experiment 2, 99 P1 sows (198.5 ± 2.7 kg) were allocated randomly according to suckled litter size (≥10 piglets), either to a CHO diet (14.3 MJ DE/kg, 19.8% crude protein) or a standard lactation diet (control; 14.2 DE MJ/kg, 19.5% crude protein) at 8 days before weaning. The CHO diet aimed to provide glucogenic content (extruded wheat, dextrose and sugar) as energy sources instead of fat sources without changing total dietary energy. Pre-prandial plasma glucose and insulin concentrations were not influenced by treatments. However, post-prandial plasma glucose and insulin concentrations and their peaks were both higher (p < .05) compared to the control treatment. Body weight loss during lactation was relatively low at 3%-4% for both treatments and did not differ between control and CHO treatments (-7.6 ± 1.6 vs -5.4 ± 1.2 kg; p > .05). Second litter size was not influenced by diet (p > .05), but the weaning-to-mating interval was shorter in CHO sows (p < .05). This study demonstrates that providing an enriched CHO diet in late lactation did influence post-weaning follicle growth but did not improve subsequent litter size. This may be due to the primiparous sows in this study not experiencing severe negative energy balance and there was no second litter syndrome in this farm which limited the ability of diet to improve sow fertility.

BRAF(V600E) Mutation is Associated with Decreased Disease-Free Survival in Papillary Thyroid Cancer.

BACKGROUND: The BRAF (V600E) mutation is a recognised molecular marker in papillary thyroid cancer (PTC), reported incidence from 30 to 80 %. BRAF(V600E) aberrantly activates the MAPK pathway, a central regulator of cell growth and proliferation. Previous studies have reported conflicting data regarding the impact of BRAF(V600E) on clinicopathological features of PTC. The study aims to determine whether BRAF(V600E) is useful as a prognostic biomarker in PTC. METHODS: A cohort study of patients undergoing surgery for PTC was undertaken. The primary outcome measure was disease-free survival. Secondary outcome measures were tumour size, nodal positivity and radioactive iodine ablation rate. All cases were re-examined to confirm PTC. Immunohistochemistry for BRAF(V600E) was performed on tissue microarrays. A single endocrine pathologist, blinded to clinicopathological data, interpreted staining. RESULTS: 496 patients with PTC were included, and 309 (62 %) were BRAF(V600E) positive. Tumour size was similar for BRAF(V600E)-positive and -negative tumours (21.3 vs. 23.2 mm, p = 0.23). BRAF(V600E)-positive patients were significantly older at first operation (mean age 45 versus 49 years, p = 0.003). BRAF(V600E)-positive PTCs had a higher rate of disease recurrence (12.9 vs. 5.6 %, p = 0.004), lymph node metastasis (44 vs. 29.4 %, p = 0.004) and extra-thyroidal extension (44 vs. 22 %, p < 0.001). Five-year disease-free survival was 89.6 % for BRAF(V600E) positive and 96.3 % for negative tumours, p < 0.001. There was no difference between groups for vascular invasion or multifocality. The mean follow-up was 57 months for both groups. CONCLUSION: BRAF(V600E) in PTC predicts an increased risk of lymph node metastasis, extra-thyroidal extension and reduced disease-free survival. It is an additional useful prognostic biomarker.

Abnormal white matter on diffusion tensor imaging in children with new-onset seizures.

The aim of this study was to use whole brain quantitative analysis to identify impaired white matter (WM) integrity using diffusion tensor imaging (DTI) in children with new-onset seizures. Thirty-five children with new-onset seizures and normal MRI were recruited. Twelve patients had generalized seizures, and 23 had partial seizures. Thirty-one healthy controls were also recruited. Whole brain fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD) and axial diffusivity (AD) maps of patients were compared to controls, corrected for multiple comparisons. There was significantly reduced FA in left postcentral, elevated RD in left posterior cingulum and right external capsule, elevated AD in left middle temporal WM and left thalamus, and reduced AD in left anterior cingulum, left temporal, and right supramarginal WM in patients relative to controls. Patients with partial epilepsy showed elevated RD in bilateral posterior cingulum, increased AD in left middle frontal, reduced AD in left temporal, right parietal and right supramarginal WM. Patients with generalized epilepsy showed increased AD in right cerebellum, and reduced AD in left anterior cingulum and left middle temporal WM. The findings indicate that impaired WM integrity with abnormal myelin and axons is present in children with new-onset seizures.

Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: To update the 2004 American Academy of Neurology/Child Neurology Society practice parameter on treatment of infantile spasms in children. METHODS: MEDLINE and EMBASE were searched from 2002 to 2011 and searches of reference lists of retrieved articles were performed. Sixty-eight articles were selected for detailed review; 26 were included in the analysis. RECOMMENDATIONS were based on a 4-tiered classification scheme combining pre-2002 evidence and more recent evidence. RESULTS: There is insufficient evidence to determine whether other forms of corticosteroids are as effective as adrenocorticotropic hormone (ACTH) for short-term treatment of infantile spasms. However, low-dose ACTH is probably as effective as high-dose ACTH. ACTH is more effective than vigabatrin (VGB) for short-term treatment of children with infantile spasms (excluding those with tuberous sclerosis complex). There is insufficient evidence to show that other agents and combination therapy are effective for short-term treatment of infantile spasms. Short lag time to treatment leads to better long-term developmental outcome. Successful short-term treatment of cryptogenic infantile spasms with ACTH or prednisolone leads to better long-term developmental outcome than treatment with VGB. RECOMMENDATIONS: Low-dose ACTH should be considered for treatment of infantile spasms. ACTH or VGB may be useful for short-term treatment of infantile spasms, with ACTH considered preferentially over VGB. Hormonal therapy (ACTH or prednisolone) may be considered for use in preference to VGB in infants with cryptogenic infantile spasms, to possibly improve developmental outcome. A shorter lag time to treatment of infantile spasms with either hormonal therapy or VGB possibly improves long-term developmental outcomes.

Reduced cortical thickness in children with new-onset seizures.

BACKGROUND AND PURPOSE: Children with new-onset seizures may have antecedent neurobiologic alterations that predispose them to developing seizures. Our aim was to evaluate hippocampal and thalamic volumes and lobar cortical thickness of children with new-onset seizures. MATERIALS AND METHODS: Twenty-nine children with new-onset seizures and normal MR imaging findings were recruited. Ten patients had generalized seizures, 19 had partial seizures, and 15 were on antiepileptic medications. Twenty-three age-matched healthy controls were also recruited. Hippocampal and thalamic volumes and lobar cortical thickness, including frontal, medial temporal, lateral temporal, parietal, cingulate, and occipital cortical thickness, were assessed by using volumetric T1-weighted imaging and were compared between patients and controls. RESULTS: There were no significant differences in hippocampal and thalamic volumes of patients with new-onset seizures, including the subgroups with generalized and partial seizures and those on and off antiepileptic medications, compared with controls (P > .01). There was significant reduction in cortical thickness in right cingulate (P = .004), right medial temporal (P = .006), and left frontal (P = .007) cortices in patients with new-onset seizures. Patients with generalized seizures did not demonstrate a significant reduction in cortical thickness (P > .01). Patients with partial seizures demonstrated a significant reduction in cortical thickness in the right frontal (P = .008), right parietal (P = .003), and left frontal (P = .007) cortices. There were no significant differences in cortical thickness among patients on or off antiepileptic medications (P > .01). CONCLUSIONS: We found reduced cortical thickness in children with new-onset seizures. Further studies are necessary to elucidate the neurobiologic relevance of these structural changes.

A giant thunderstorm on Saturn.

Lightning discharges in Saturn's atmosphere emit radio waves with intensities about 10,000 times stronger than those of their terrestrial counterparts. These radio waves are the characteristic features of lightning from thunderstorms on Saturn, which last for days to months. Convective storms about 2,000 kilometres in size have been observed in recent years at planetocentric latitude 35° south (corresponding to a planetographic latitude of 41° south). Here we report observations of a giant thunderstorm at planetocentric latitude 35° north that reached a latitudinal extension of 10,000 kilometres-comparable in size to a 'Great White Spot'-about three weeks after it started in early December 2010. The visible plume consists of high-altitude clouds that overshoot the outermost ammonia cloud layer owing to strong vertical convection, as is typical for thunderstorms. The flash rates of this storm are about an order of magnitude higher than previous ones, and peak rates larger than ten per second were recorded. This main storm developed an elongated eastward tail with additional but weaker storm cells that wrapped around the whole planet by February 2011. Unlike storms on Earth, the total power of this storm is comparable to Saturn's total emitted power. The appearance of such storms in the northern hemisphere could be related to the change of seasons, given that Saturn experienced vernal equinox in August 2009.

Abnormal axial diffusivity in the deep gray nuclei and dorsal brain stem in infantile spasm treated with vigabatrin.

We evaluated the DTI changes in the deep gray nuclei and dorsal brain stem, which demonstrated abnormal T2 and/or diffusion signal intensity, in 6 patients with infantile spasm treated with vigabatrin compared with 6 age-matched controls. Regions of interest were placed in the globi pallidi, thalami, and dorsal brain stem; FA, trace, D(‖), and D(⊥) were measured. Patients on vigabatrin had significantly lower FA in both globi pallidi (P = .01) and the dorsal brain stem (P < .01), significantly lower trace in both globi pallidi (P = .01) and the thalami (P = .02 and .01 for right and left, respectively), and significantly lower D(‖) in both globi pallidi (P ≤ .01), the thalami (P < .01), and the dorsal brain stem (P = .03). There were no significant differences in D(⊥) of the globi pallidi, thalami, or dorsal brain stem in patients compared with controls. The findings suggest that axonal changes play a greater role in the observed abnormal signal intensity, with lesser contribution from myelin changes.

Chikungunya fever in Singapore: acute clinical and laboratory features, and factors associated with persistent arthralgia.

BACKGROUND: In Singapore, the first local outbreak of chikungunya was reported in January 2008, followed by a larger outbreak occurred in August 2008. During the initial outbreak period, a strict containment strategy was adopted and all chikungunya PCR-confirmed cases were isolated and hospitalised at the designated national outbreak management centre. OBJECTIVES: To detail daily clinical and laboratory features of chikungunya cases during acute illness, and determine factors associated with persistent arthralgia at week 6. STUDY DESIGN: Prospective cohort study of patients with PCR-confirmed chikungunya infection and hospitalised within 5 days of illness onset, from 1st August to 10th November 2008. Post-hospital discharge, patients were followed up at the specialist outpatient clinic, and assessed for arthralgia at week 6 of illness. RESULTS: Of the 97 patients in the study, the most common presenting symptoms were fever (89.7%) and arthralgia (87.6%). Mean nadir leukocyte and platelet counts were 3.5(SD 1.9) × 10(9)/L and 165(SD 42) × 10(9)/L respectively. Of the 39 patients who were evaluated at week 6, 14 (35.9%) had persistent arthralgia. Those with persistent arthralgia tended to be females (p = 0.003), and had a lower peak creatinine level (p = 0.036) than those without. Peak viral load (p = 0.664), and duration of fever (p = 0.056) and viremia (p = 0.55) respectively, were not significantly different between those with persistent arthralgia and those without. CONCLUSIONS: This study details the daily clinical and laboratory features of chikungunya patients during acute illness. Those with persistent arthralgia tended to be females, who had significantly lower peak creatinine level.

Diffusion tensor imaging of commissural and projection white matter in tuberous sclerosis complex and correlation with tuber load.

BACKGROUND AND PURPOSE: Cortical and white matter changes have been identified outside the MR imaging-visible cortical/subcortical tubers in the tuberous sclerosis complex. The aim of this study was to evaluate DTI changes in the corpus callosum and internal capsules and to correlate the DTI changes with cortical/subcortical tuber load. MATERIALS AND METHODS: Twelve TSC patients and 23 controls underwent MR imaging including DTI. FA, trace, D( ||), and D() of genu and splenium of corpus callosum and right and left internal capsules were assessed. The number and volume of cortical/subcortical tubers were correlated with DTI indices of corpus callosum and internal capsules. RESULTS: In the genu and splenium, FA was lower and trace (P < .01) and D() were higher (P < .01), and in the internal capsules, trace was higher (P = .04) in TSC patients compared with controls. The total tuber volume correlated positively with trace of genu (r = 0.77, P < .01) and splenium (r = 0.69, P = .01) and with D() of splenium (r = 0.68, P = .01), and negatively with FA of splenium (r = -0.60, P = .04) of corpus callosum. The left and right hemispheric tuber volume correlated positively with trace of left (r = 0.56, P = .05) and right (r = 0.67, P = .02) internal capsules. CONCLUSIONS: Our findings of reduced FA, elevated trace, and elevated D() in the corpus callosum and internal capsules may be related to abnormalities in myelin. The correlations between tuber volume and DTI indices in corpus callosum and internal capsules suggested that more extensive malformation as demonstrated by larger tuber load was more likely to be associated with more severe DTI changes in the commissural and projection white matter.

Depth of a strong jovian jet from a planetary-scale disturbance driven by storms.

The atmospheres of the gas giant planets (Jupiter and Saturn) contain jets that dominate the circulation at visible levels. The power source for these jets (solar radiation, internal heat, or both) and their vertical structure below the upper cloud are major open questions in the atmospheric circulation and meteorology of giant planets. Several observations and in situ measurements found intense winds at a depth of 24 bar, and have been interpreted as supporting an internal heat source. This issue remains controversial, in part because of effects from the local meteorology. Here we report observations and modelling of two plumes in Jupiter's atmosphere that erupted at the same latitude as the strongest jet (23 degrees N). The plumes reached a height of 30 km above the surrounding clouds, moved faster than any other feature (169 m s(-1)), and left in their wake a turbulent planetary-scale disturbance containing red aerosols. On the basis of dynamical modelling, we conclude that the data are consistent only with a wind that extends well below the level where solar radiation is deposited.

A unique strategy of host colony exploitation in a parasitic ant: workers of Polyrhachis lama rear their brood in neighbouring host nests.

The formicine ant Polyrhachis lama is a social parasite, exploiting its ponerine host ant species Diacamma sp. In most social parasitic associations, the parasitic species are closely related to their host species group, evolving directly from independent ancestors of the host species. However, in the Polyrhachis lama- Diacamma sp. association, the associated species belong to different ant subfamilies. Based on preliminary field surveys, we had presumed that P. lama might have given up its reproductive division of labour, i.e. workers would be able to produce males as well as workers and females parthenogenetically. In this study, this hypothesis was disproved: Polyrhachis lama workers cannot be fertilized and are only able to produce males. In the host-parasite association originating from nests possessing a P. lama queen, workers penetrate surrounding Diacamma sp. nests, carrying brood for rearing within these satellite nests. In this peculiar way, a single P. lama colony is able to exploit several Diacamma sp. colonies simultaneously.

Measurement of TG synthesis and turnover in vivo by 2H2O incorporation into the glycerol moiety and application of MIDA.

A method is presented for measurement of triglyceride (TG) synthesis that can be applied to slow-turnover lipids. The glycerol moiety of TG is labeled from 2H2O, and mass isotopomer distribution analysis (MIDA) is applied. Mice and rats were given 4-8% 2H2O in drinking water; TG-glycerol was isolated from adipose and liver during < or =12-wk of 2H2O labeling. Mass isotopomer abundances in the glycerol moiety of TG were measured by GC-MS. The combinatorial pattern of isotopomers revealed the number of H atoms in glycerol incorporating label from 2H2O (n) to be 3.8-4.0 of a possible 5 for adipose tissue and 4.6-4.8 for liver TG. Hepatic TG-glycerol in fact reached 97% predicted maximal value of label incorporation (4.4-4.6 x body 2H2O enrichment), indicating near-complete replacement of the liver TG pool. Label incorporation into adipose tissue revealed turnover of mesenteric TG to be faster (k = 0.21 day-1) than other depots (k = 0.04-0.06 day-1) in mice. TG isolated from subcutaneous depots of growing adult rats plateaued at 85-90% of calculated maximal values at 12 wk (k = 0.05 day-1), excluding significant dilution by unlabeled alpha-glycerol phosphate. Turnover of plasma TG, modeled from 2H incorporation over 60 min, was 0.06 min-1 (half-life 11.5 min). In summary, use of 2H2O labeling with MIDA of TG-glycerol allows measurement of new alpha-glycerol phosphate-derived TG synthesis and turnover. The hypothesis that mesenteric TG is more lipolytically active than other depots, previously difficult to prove by isotope dilution techniques, was confirmed by this label incorporation approach.

Regulation of the nitric oxide synthase-nitric oxide-cGMP pathway in rat mesenteric endothelial cells.

Most of the available data on the nitric oxide (NO) pathway in the vasculature is derived from studies performed with cells isolated from conduit arteries. We investigated the expression and regulation of components of the NO synthase (NOS)-NO-cGMP pathway in endothelial cells from the mesenteric vascular bed. Basally, or in response to bradykinin, cultured mesenteric endothelial cells (MEC) do not release NO and do not express endothelial NOS protein. MEC treated with cytokines, but not untreated cells, express inducible NOS (iNOS) mRNA and protein, increase nitrite release, and stimulate cGMP accumulation in reporter smooth muscle cells. Pretreatment of MEC with genistein abolished the cytokine-induced iNOS expression. On the other hand, exposure of MEC to the microtubule depolymerizing agent colchicine did not affect the cytokine-induced increase in nitrite formation and iNOS protein expression, whereas it inhibited the induction of iNOS in smooth muscle cells. Collectively, our findings demonstrate that MEC do not express endothelial NOS but respond to inflammatory stimuli by expressing iNOS, a process that is blocked by tyrosine kinase inhibition but not by microtubule depolymerization.

Infections associated with steroid use.

Patients receiving chronic steroids have an increased susceptibility to many different types of infections. The risk of infection is related to the dose of steroid and the duration of therapy. Although pyogenic bacteria are the most common pathogens, chronic steroid use increases the risk of infection with intracellular pathogens such as Listeria, many fungi, the herpes viruses, and certain parasites. Clinicians should consider both common and unusual opportunistic infections in patients receiving chronic steroids.