Ichthyosis, psoriasiform dermatitis, and recurrent fungal infections in patients with biallelic mutations in PERP.

BACKGROUND: Germline autosomal dominant and autosomal recessive mutations in PERP, encoding p53 effector related to PMP-22 (PERP), a component of epidermal desmosomes, have been associated with a spectrum of keratodermas. Monoallelic nonsense mutations cause Olmsted syndrome with severe periorificial keratoderma and palmoplantar keratoderma (PPK). Biallelic recessive frameshift and missense mutations are associated with milder forms of the disease, including generalised erythrokeratoderma and PPK. OBJECTIVES: To add new insights into the genotype-phenotype correlations as a consequence of PERP mutations and to provide a comprehensive review of the literature. METHODS: Among 26 previously unresolved families within a cohort of 180 extended Iranian families with syndromic or non-syndromic ichthyosis, two families with shared clinical features were examined by whole-exome sequencing and genome-wide homozygosity mapping. Mycological and dermatopathological studies were performed to further characterise their atypical phenotypic presentations. RESULTS: In two unrelated multiplex consanguineous families affected by ichthyosis, two novel biallelic PERP variants, NM_022121.5, c.89T > C, p.Leu30Pro and c.466G > C, p.Gly156Arg, located inside of genomic homozygosity regions of the probands were detected. Interestingly, some patients had areas of scaly psoriasiform plaques on the background of generalised ichthyosis that appeared during active cutaneous fungal infections. Mycological examinations of these lesions revealed infections caused by Candida albicans, Epidermophyton floccosum, or Trichophyton rubrum. Histopathology of the psoriasiform lesions shared some features with psoriasis, which when combined with clinical presentation, led to incorrect diagnosis of guttate psoriasis or pustular psoriasis. CONCLUSIONS: PERP variants in ichthyosis patients can confer susceptibility to recalcitrant cutaneous fungal infections. Additionally, patients with episodic psoriasiform dermatitis in the setting of keratoderma should be considered for PERP genotyping and cutaneous fungal examinations.

Production effects and bioavailability of N-acetyl-l-methionine in lactating dairy cows.

Two experiments were conducted to investigate the production effects of N-acetyl-l-methionine (NALM; experiment 1) and to estimate its bioavailability (BA) and rumen escape (RE; experiment 2), respectively, in lactating dairy cows. In experiment 1, 18 multiparous Holstein cows were used in a replicated, 3 × 3 Latin square design experiment with three 28-d periods. Treatments were (1) basal diet estimated to supply 45 g/d digestible Met (dMet) or 1.47% of metabolizable protein (MP; control), (2) basal diet top-dressed with 32 g/d of NALM to achieve dMet supply of 2.2% of MP, and (3) basal diet top-dressed with 56 g/d of NALM to achieve dMet supply of 2.6% of MP. The NALM treatments supplied estimated 17 and 29 g/d dMet from NALM, respectively, based on manufacturer's specifications. In experiment 2, 4 rumen-cannulated lactating Holstein cows were used in a 4 × 4 Latin square design experiment with four 12-d periods. A 12-d period for baseline data collection and 4 d for determination of RE of NALM preceded the Latin square experiment. For determination of RE, 30 g of NALM were dosed into the rumen simultaneously with Cr-EDTA (used as a rumen fluid kinetics marker) and samples of ruminal contents were collected at 0 (before dosing), 1, 2, 4, 6, 8, 10, 14, 18, and 24 h after dosing. Rumen escape of NALM was calculated using the estimated passage rate based on the measured Cr rate of disappearance. Bioavailability of abomasally dosed NALM was determined using the area under the curve of plasma Met concentration technique. Two doses of l-Met (providing 7.5 and 15 g of dMet) and 2 doses of NALM (11.2 and 14.4 g of dMet) were separately pulse-dosed into the abomasum of the cows and blood was collected from the jugular vein for Met concentration analysis at 0 (before dosing), 1, 2, 4, 6, 8, 10, 12, 14, 18, and 24 h after dosing. Supplementation of NALM did not affect DMI, milk yield, feed efficiency, or milk protein and lactose concentrations and yields in experiment 1. Milk fat concentration and energy-corrected milk yield decreased linearly with NALM dose. Plasma Met concentration was not affected by NALM dose. The estimated relative BA of abomasally dosed NALM (experiment 2) was 50% when dosed at 14.4 g/cow (11.2 g/d dMet from NALM) and 24% when dosed at 28.8 g/cow (14.4 g/d dMet from NALM). The estimated RE of NALM was 19% based on the measured kp of Cr at 11%/h. The total availability of ingested NALM was estimated at 9.5% for the lower NALM dose when taking into account RE (19%) and bioavailability in the small intestine (50%). Overall, NALM supplementation to mid-lactation dairy cows fed a MP-adequate basal diet below NRC (2001) recommendations (45 g/d or 1.47% Met of MP) decreased milk fat and energy-corrected milk yields but did not affect milk or milk true protein yields. Further evaluation of BA of NALM at different doses is warranted. In addition, intestinal conversion of NALM to Met needs additional investigation to establish a possible saturation of the enzyme aminoacylase I at higher NALM doses.

Sub-pixel high-resolution imaging of high-energy x-rays inspired by sub-wavelength optical imaging.

We have developed and demonstrated an image super-resolution method-XR-UNLOC: X-Ray UNsupervised particle LOCalization-for hard x-rays measured with fast-frame-rate detectors that is an adaptation of the principle of photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), which enabled biological fluorescence imaging at sub-optical-wavelength scales. We demonstrate the approach on experimental coherent Bragg diffraction data measured with 52 keV x-rays from a nanocrystalline sample. From this sample, we resolve the fine fringe detail of a high-energy x-ray Bragg coherent diffraction pattern to an upsampling factor of 16 of the native pixel pitch of 30 µm of a charge-integrating fastCCD detector. This was accomplished by analysis of individual photon locations in a series of "nearly-dark" instances of the diffraction pattern that each contain only a handful of photons. Central to our approach was the adaptation of the UNLOC photon fitting routine for PALM/STORM to the hard x-ray regime to handle much smaller point spread functions, which required a different statistical test for photon detection and for sub-pixel localization. A comparison to a photon-localization strategy used in the x-ray community ("droplet analysis") showed that XR-UNLOC provides significant improvement in super-resolution. We also developed a metric by which to estimate the limit of reliable upsampling with XR-UNLOC under a given set of experimental conditions in terms of the signal-to-noise ratio of a photon detection event and the size of the point spread function for guiding future x-ray experiments in many disciplines where detector pixelation limits must be overcome.

The concordance rate of non-chromosomal congenital malformations in twins based on zygosity: a retrospective cohort study.

OBJECTIVE: To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital in Korea. POPULATION: Twin pairs born at Seoul National University Hospital between 2001 and 2019. METHODS: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. MAIN OUTCOME MEASURES: Concordance rate of congenital malformations in twin pairs based on zygosity. RESULTS: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. CONCLUSIONS: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. TWEETABLE ABSTRACT: Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems.

Cell-free culture supernatant of Lactobacillus curvatus Wikim38 inhibits RANKL-induced osteoclast differentiation and ameliorates bone loss in ovariectomized mice.

This study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of Lactobacillus curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density in ovariectomized mice in µ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation by the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.

Initial experience with a suprapubic single-port robotic right hemicolectomy in patients with colon cancer.

BACKGROUND: We developed a novel suprapubic single-port robotic right hemicolectomy (spRHC) procedure for patients with right colon cancer using a da Vinci SP Surgical System. The aim of this study was to determine the safety and feasibility of this technique. METHODS: We performed the spRHC procedure on five patients with right colon cancers between July and September 2020. All procedures including colon mobilization, D3 lymphadenectomy, and intracorporeal anastomosis were completed using the single-port robotic platform through a mini-transverse suprapubic incision and an additional assistant port. Data regarding patient characteristics, perioperative outcomes and pathologic results were analyzed. RESULTS: Four of the five patients were males. The median age was 69 years (range, 58-77 years).Two patients received preoperative chemotherapy for advanced colon cancer. The median total operative time was 160 min (range, 150-240 min). The median docking time was 4 min 40 s (range, 2 min 10 s-5 min 10 s). The median console time was 105 min (range, 100-120 min). There were no conversions to multiport or open surgeries. The median hospital stay was 7 days (range, 5-12 days). One patient experienced a wound infection. The median number of harvested lymph nodes was 41 (range, 39-50 lymph nodes). CONCLUSIONS: SpRHC is safe and feasible. However, further comparative studies are needed to assess whether this procedure can provide patients with significant benefits compared with multiport robotic surgery.

An initial experience with a novel technique of single-port robotic resection for rectal cancer.

BACKGROUND: The da Vinci single-port (SP) system is designed to facilitate single-incision robotic surgery in a narrow space. We developed a new procedure of rectal resection using this system. The aim of the present study was to evaluate the technical feasibility and safety of SP robotic rectal resection for rectal cancer patients based on our initial experience. METHODS: A study was conducted on consecutive patients with mid or low rectal cancer who had SP robotic resection at our institution between July and September 2020. The demographic characteristics, perioperative data, and pathology results of the patients were retrospectively analyzed. RESULTS: There were 5 patients (3 males, 2 females, median age 57 years (range 36-73 years). The median tumor height from the anal verge was 4 cm (range 3-5 cm). Two patients received preoperative chemoradiotherapy for advanced rectal cancer. A single docking was conducted, and the median docking time was 4 min 20 s (range 3 min 30 s to 5 min). The median total operation time was 195 min (range 155-240 min), and the median time of pelvic dissection was 45 min (range 36-62 min). All patients had circumferential and distal tumor-free resection margins. One patient experienced an anastomosis-related complication. The median duration of hospital stay was 7 days (range 7-8 days). CONCLUSIONS: Our initial experience suggests that SP robotic rectal resection is safe and feasible. Further clinical trials comparing SP and multiport robotic rectal resection should be conducted to verify the superior aspects of this new system.

Long-term clinical outcomes of total mesorectal excision and selective lateral pelvic lymph node dissection for advanced low rectal cancer: a comparative study of a robotic versus laparoscopic approach.

BACKGROUND: The long-term outcomes of minimally invasive lateral pelvic lymph node dissection (LPND) are not completely known. The aim of this study was to compare long-term outcomes between robotic and laparoscopic LPND in low rectal cancer patients with suspected lymph node metastasis in the pelvic sidewall. METHODS: We retrospectively reviewed the records of all rectal cancer patients who had laparoscopic or robotic total mesorectal excision (TME) with LPND between March 2006 and June 2016. Stage IV patients were excluded. The outcomes of patients who had laparoscopic and robotic TME with LPND were compared. RESULTS: Twenty-nine patients had laparoscopic LPND and 70 had robotic LPND. No significant differences in patient characteristics were observed between the two groups. The urinary retention rate was lower in the robotic group than in the laparoscopic group (7.1% vs. 24.1%; p = 0.043). During a median follow-up of 44.3 months, the overall recurrence rates were 48.3% and 31.4% in the laparoscopic and robotic groups, respectively (p = 0.175). The 5-year disease-free survival rates were 50.4% and 67.0% in the laparoscopic and robotic groups, respectively (p = 0.227). The 5-year overall survival rates were 65.0% and 92.2% in the laparoscopic and robotic groups, respectively (p = 0.017). CONCLUSIONS: Robotic TME with LPND is safe and feasible. In particular, it is associated with lower urinary retention. Robotic TME with LPND might yield a similar local recurrence rate and 5-year disease-free survival, but favorable long-term overall survival as compared to the laparoscopic approach. However, considering the retrospective nature and both major variables of TME and LPND involved together, this should be cautiously interpreted.

Investigation of photodarkening in tandem-pumped Yb-doped fibers.

Investigation of photodarkening (PD) in Yb-doped fibers tandem-pumped at 1018 nm is reported. For a homemade Yb-doped aluminosilicate double-clad fiber (YADF), the transmitted power of a 633 nm probe beam is reduced by 2.4% over 2 hours for the tandem pumping configuration at 1018 nm, which is significantly smaller than 33.3% for a laser diode (LD) pumping at 976 nm. A tandem-pumped Yb fiber amplifier also shows a much smaller decrease in the amplified output power over time than a LD-pumped Yb fiber amplifier. Based on fluorescence spectra of the YADF, we can not only associate PD of the YADF to intrinsic oxygen deficiency centers or Tm3+ impurities but also confirm the impact of the excited Yb3+ ion density on PD. The benefits of the tandem pumping in a high-power Yb fiber laser system will be discussed.

Transverse Single-Spin Asymmetry for Very Forward Neutral Pion Production in Polarized p+p Collisions at sqrt[s]=510 GeV.

Transverse single-spin asymmetries of very forward neutral pions generated in polarized p+p collisions allow us to understand the production mechanism in terms of perturbative and nonperturbative strong interactions. During 2017, the RHICf Collaboration installed an electromagnetic calorimeter in the zero-degree region of the STAR detector at the Relativistic Heavy Ion Collider (RHIC) and measured neutral pions produced at pseudorapidity larger than 6 in polarized p+p collisions at sqrt[s]=510 GeV. The large nonzero asymmetries increasing both in longitudinal momentum fraction x_{F} and transverse momentum p_{T} have been observed at low transverse momentum p_{T}<1 GeV/c for the first time, at this collision energy. The asymmetries show an approximate x_{F} scaling in the p_{T} region where nonperturbative processes are expected to dominate. A non-negligible contribution from soft processes may be necessary to explain the nonzero neutral pion asymmetries.

Protopanaxatriol inhibits melanin synthesis through inactivation of the pCREB-MITF-tyrosinase signalling pathway in melanocytes.

Ginsenosides are major active components of ginseng, and have diverse pharmacological properties in traditional medicine. Recent reports have shown that ginsenosides modify skin physiology and mitigate skin disorders such as photoageing and hyperpigmentation. We evaluated the antimelanogenic efficacy of protopanaxatriol, a major category of ginsenosides, as a depigmenting agent. Protopanaxatriol significantly reduced intracellular and extracellular melanin content in a concentration-dependent manner in B16 melanoma cells treated with α-melanocyte-stimulating hormone. In normal human epidermal melanocytes, protopanaxatriol clearly decreased melanin synthesis and dendrite elongation. In addition, protopanaxatriol dramatically suppressed the expression of genes encoding the melanogenic proteins tyrosinase, tyrosinase-related protein-1 and -2, and microphthalmia-associated transcription factor through dephosphorylation of cAMP response element-binding protein. These results suggest that protopanaxatriol could be an effective candidate anti-melanogenic agent.

The impact of robotic surgery on quality of life, urinary and sexual function following total mesorectal excision for rectal cancer: a propensity score-matched analysis with laparoscopic surgery.

AIM: Quality of life (QoL) and functional outcomes are at risk of being impaired after rectal surgery, but there has been no large prospective study to thoroughly assess QoL according to surgical approach. We have investigated the impact of laparoscopic and robotic total mesorectal excision (TME) on QoL and functional outcomes. METHOD: Patients undergoing laparoscopic or robotic TME for rectal cancer between 2009 and 2013 were prospectively included in this questionnaire-based survey of QoL together with variations in urinary and sexual function. A propensity score analysis was retrospectively conducted to compare outcomes between groups in a cohort matched 1:1 for age, sex, body mass index, preoperative chemoradiation status and tumour height. The survey was performed preoperatively and 3, 6 and 12 months after surgery. RESULTS: Global health status/QoL was similar between the two groups for 130 matched pairs, but the robotic group showed better role, emotional and social functioning and experienced less fatigue and financial difficulty. International Prostatic Symptom Scores in men increased postoperatively, with significantly less impairment in the robotic group at 6 months. These scores were comparable to preoperative scores at 6 months in the robotic group and at 12 months in the laparoscopic group. Of 48 sexually active men in each group, International Index of Erectile Function-5 scores decreased postoperatively, returning to preoperative levels at 6 months in the robotic group and at 12 months in the laparoscopic groups. CONCLUSION: The robotic approach for TME was associated with less impairment of urinary and sexual function; QoL was comparable to the laparoscopic approach.

Influence of supplementing a methionine derivative, N-acetyl-l-methionine, in dairy diets on production and ruminal fermentation by lactating cows during early to mid lactation.

The present study investigated production responses and ruminal fermentation characteristics of lactating dairy cows when supplemented with N-acetyl-l-Met (NALM) as a source of rumen-protected Met in metabolizable protein (MP)-deficient (MPD) or MP-adequate diet (MPA). Eight lactating dairy cows (53 ± 10.4 d in milk, average ± standard deviation) were blocked by parity and days in milk, and the experiment was performed in a replicated 4 × 4 Latin square design. Within each square, cows were randomly assigned to a sequence of 4 diets during each of the four 21-d periods (14 d of treatment adaptation and 7 d of data collection and sampling). A 2 × 2 factorial arrangement was used; MPD or MPA was combined without or with NALM: MPD without NALM, MPD with NALM (MPD+NALM), MPA without NALM, and MPA with NALM (MPA+NALM). A NALM product was supplemented in the MPD+NALM and the MPA+NALM at 30 g/cow per d. Supplementation of NALM did not affect dry matter intake (DMI) and milk yield regardless of MP concentration. In addition, supplementing NALM resulted in a similar milk true protein concentration and yield. In contrast, NALM supplementation increased milk fat concentration and yield and 3.5% fat-corrected milk yield and tended to increase energy-corrected milk yield regardless of MP difference. Additionally, trends were observed for increased 3.5% fat-corrected milk yield/DMI and energy-corrected milk yield/DMI, and the positive effects were greater under the MPA than the MPD diet, resulting in trends toward interactions between MP and NALM. Dietary treatments had similar effects on ruminal fermentation characteristics and microbial protein yield. Plasma concentration of Met increased under the MPD but not the MPA diet, leading to an MP × NALM interaction. Overall results in the current study suggest that NALM exerted a minor influence on ruminal metabolism, but increased milk fat concentration, resulting in increases in milk fat yield and feed efficiency. Yet, potential effects of NALM on intermediary metabolism between the gastrointestinal tract, the liver, and the mammary gland need to be explored to understand utilization efficiency for production of dairy cows.

Real-time tracking of a surface ship using a bottom-mounted horizontal array.

The cascade of blind deconvolution and array invariant has been successful to localize and track a surface ship radiating random waveforms, using a 56-m long vertical array in 100-m deep shallow water. In this paper, it is shown that a 60-m long, bottom-mounted horizontal array can be utilized for blind deconvolution to extract the Green's functions from the same ship (100-800 Hz), in conjunction with the array invariant for source-range estimation. The additional information obtained with a horizontal array is the source bearing (azimuth angle, ϕ) from the well-resolved ray angle identified for blind deconvolution to extract the phase component of the unknown source waveforms. The overall tracking performance shows good agreement with global positioning system (GPS) measurements to less than 11% in terms of standard deviation of relative range error at ranges of 0.3-1.5 km, except when the ship is around the broadside (e.g., | ϕ | < 25 ° ) of the horizontal array. On the other hand, the source bearings are in excellent agreement with the GPS data except near the endfire due to the lower angular resolution. The potential for simultaneous localization of multiple ships is also discussed.

ALK-positive anaplastic large-cell lymphoma with primary bone involvement: A rare case and review of the literature.

Primary bone lymphoma (PBL) is an uncommon type of extranodal lymphoma involvement. An anaplastic large-cell lymphoma (ALCL) is an extremely rare type of PBL, and it remains unclear whether ALCLs that primarily involve the bone exhibit favourable or unfavourable biological behaviour, and whether they are similar to ALCLs in general, or not. We reported a case of ALK-positive ALCL with primary bone involvement, and reviewed the clinicopathological features of 22 previously reported cases. An ALCL with primary bone involvement mostly affects younger patients with a preponderant towards the involvement of axial-bone. The prognosis of an ALCL that primarily involves bone is unfavourable, compared with PBL generally. The ALK-positive ALCLs in PBLs had less decedents than the ALK-negative ALCLs with a statistical non-significance (p=0.198).

Infiltrated photonic crystals for light-trapping in CuInSe2 nanocrystal-based solar cells.

Solution processable nanocrystal solar cells combine the advantages of low-cost printing and wide range of accessible absorber materials, however high trap densities limit performance and layer thickness. In this work we develop a versatile route to realize the infiltration of a photonic crystal, with copper indium diselenide nanocrystal ink. The photonic crystal allows to couple incident light into pseudo-guided modes and thereby enhanced light absorption. For the presented design, we are able to identify individual guided modes, explain the underlying physics, and obtain a perfect match between the measured and simulated absorption peaks. For our relatively low refractive index layers, a 7% maximum integrated absorption enhancement is demonstrated.

Bone mineral density among Korean females aged 20-50 years: influence of age at menarche (The Korea National Health and Nutrition Examination Survey 2008-2011).

To evaluate a possible correlation between bone mineral density (BMD) and age at menarche, the present study used the BMD dataset of the Korea National Health and Nutrition Examination Survey IV-V (KNHANES IV-V). Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. INTRODUCTION: To investigate any correlation between bone mineral density (BMD) and age at menarche in Korean females using data from the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-V; 2008-2011). METHODS: In total, 37,753 individuals participated in health examination surveys between 2008 and 2011. A total of 5032 premenopausal females aged 20-50 years were eligible. Age, height, weight, and age at menarche were assessed. RESULTS: Results from the univariate linear regression and analysis of covariance (ANCOVA) indicated that age (per 1 year), height (per 1 cm), weight (per 1 kg), exercise (per 1 day/week), familial osteoporosis history (yes), parity (n = 0 to ≥4), and menarche age distribution were associated with BMD of the total femur, femur neck, and lumbar spine. After stratifying the bone area and adjusting for age, parity, alcohol intake, smoking, exercise, and familial osteoporosis history, no effect was seen for the total femur or femur neck. Age at menarche 16~17 and ≥18 years groups were associated with BMD of the lumbar spine only. CONCLUSIONS: Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. Females with late menarche may achieve lower peak bone mass at some skeletal sites, which may put them at greater risk for osteoporosis in later life.

Structural explanation of poor prognosis of amyotrophic lateral sclerosis in the non-demented state.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS), a motor neuron disease, is associated with various cortical symptoms including mild cognitive decline with behavior changes, suggesting the involvement of extra-motor areas in ALS. Our aim was to investigate the specific patterns of brain atrophy in sporadic, impaired ALS patients without commonly known genetic mutations using voxel-based morphometry. MATERIALS AND METHODS: Forty-seven patients with sporadic ALS and 28 age-matched healthy controls were recruited. ALS participants were divided into three groups according to comprehensive neuropsychological testing: pure (ALS-pure), cognitive impairment (ALSci) and behavioral impairment (ALSbi). Quantitative comparison of brain atrophy patterns was performed amongst these three groups using voxel-based analysis. All analyses were adjusted for total intracranial volume, age, sex, disease duration and functional disability score. RESULTS: The ALSci group exhibited decreased volume in the left cerebellum, fusiform gyrus, optic radiations and corticospinal tracts compared to healthy controls. ALSci patient imaging showed decreased brain volume in the bilateral cerebellum, right putamen gray matter and bilateral superior longitudinal fasciculi white matter compared to pure ALS patients (P < 0.001 uncorrected, corrected for the entire volume). Compared to healthy controls, ALS-pure and ALSbi groups did not show any significant volume changes in gray and white matter. CONCLUSIONS: These findings also support the hypothesis that ALS pathogenesis has a dual focality of onset (cortex and anterior horn) with contiguous spread outwards. Additionally, neuropsychological features may be an important predictor of progression and survival rates in ALS.

Changes in cognitive function and brain glucose metabolism in elderly women with subjective memory impairment: a 24-month prospective pilot study.

OBJECTIVES: Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI. MATERIALS AND METHODS: Clinical evaluation, comprehensive neuropsychological test, and 18 F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. RESULTS: All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: -0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (ß = 0.43, P = 0.02). CONCLUSIONS: Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time.