ObjectiveThe

\n\nObjective\n\nThe selleck objective of this study was to evaluate the response to autologous melanocyte-keratinocytes suspension transplantation in cases of stable vitiligo.\n\nMethods\n\nA total of 25 cases of vitiligo were treated by autologous melanocyte-keratinocytes suspension transplantation. After 6-17 months, patients’ response was evaluated according to the extent of pigmentation (excellent 90-100%, good 50-89%, fair 20-49% and poor response < 20%).\n\nResults\n\nOf

the 25 patients treated, 22 continued the follow-up period. Five (23%) patients showed excellent response, 7 (32%) good, 6 (27%) fair

and 4(18%) showed poor response.\n\nConclusion\n\nUnlike transplantation of cultured melanocytes, which requires experience in culture technique, autologous melanocyte-keratinocytes suspension transplantation is an easy economic technique, which may be used in resistant areas of stable vitiligo.”
“Previous studies Danusertib nmr have examined the effects of heating on teeth; however, none have identified characteristics that allow analysts to differentiate traumatic from heat-induced fractures. This study examined our ability to discern notable differences in preincineration traumatic fractures and heat-induced fractures in postincineration dentition. Twelve anterior dental specimens were subjected to blunt force trauma while a second set were not. All 24 samples were then incinerated in a muffle furnace at a peak temperature (900 degrees C) consistent with house fires. The specimens were subsequently examined with a scanning electron microscope to identify and compare heat-induced and traumatic fractures. The results obtained during examination yielded BMS-777607 nmr no differences between the features displayed by specimens that had been inflicted with

preincineration trauma and those that did not. Unlike bone, distinguishing features for the differentiation of traumatic and heat-induced fractures could not be compiled.”
“Introduction: The aim of this study was to determine the relationship between nursing students’ epistemologic beliefs and locus of control, and the research was conducted at Istanbul University Florence Nightingale School of Nursing with 350 nursing students.\n\nMethods: Data were collected using the Turkish version of the Epistemological beliefs questionnaire and Rotter’s Internal-External Locus of Control Scale. In the data analysis number, percentage, mean, correlation analysis, one-way analysis of variance and Tukey HSD test were used.

Across decreasing tertiles of colony-forming units,

there

Across decreasing tertiles of colony-forming units,

there was a progressive increase in median coronary artery calcification and abdominal aortic calcification BMS-777607 scores. In multivariable analyses adjusting for traditional cardiovascular risk factors, each 1-SD increase in colony-forming units was associated with a approximate to 16% decrease in coronary artery calcification (P=0.02) and 17% decrease in abdominal aortic calcification (P=0.03). In contrast, neither CD34(+) /KDR(+) nor CD34(+) variation was associated with significant differences in coronary or aortic calcification.\n\nConclusions-In this large, community-based sample of men and women, lower colony-forming unit number was associated with a higher burden

of subclinical atherosclerosis in the coronary arteries and aorta. Decreased angiogenic potential could contribute to the development of atherosclerosis in humans. (Circulation. 2010;122:1176-1182.)”
“The proportion of group D streptococcal infective endocarditis (IE) (predominantly due to Streptococcus gallolyticus) and the incidence of colorectal cancer are higher in France than in most European countries. We assumed that this could be explained by a high group D streptococci (GDS) fecal carriage rate. The aims of this study were to re-assess the GDS fecal carriage rate in France and its relationship with colorectal Selleck Linsitinib cancer. Consecutive adult subjects who were to undergo a complete colonoscopy were invited to participate. GDS were searched in subjects’ stools before their colonoscopy using biomolecular FG-4592 cell line techniques. Colonoscopic findings were sorted into four subgroups: normal colonoscopy, non-tumoral lesions, benign tumors, and premalignant/malignant tumors. GDS fecal carriages were calculated overall and in each subgroup and compared. The data from 259 subjects were analyzed. GDS were identified in the feces of 12 subjects, with the following distribution: S. lutetiensis (n =

9), S. pasteurianus (n = 2), and S. gallolyticus (n = 1). This accounted for an overall GDS fecal carriage rate of 4.6 %. The GDS fecal carriage rate was 6 % in case of normal colonoscopy, 1.3 % in case of non-tumoral lesions, 3.2 % in case of benign tumors, and 11 % in case of premalignant/malignant tumors. These four percentages were not statistically different. The GDS fecal carriage rate was lower than expected, which did not confirm our working hypothesis. Most strains belonged to S. bovis biotype II, while S. gallolyticus was found only once. These findings suggest that different GDS play different roles in the etiopathogenesis of IE and colorectal cancer.”
“Background: Spacer grafts in the eyelid are used in both reconstructive and aesthetic procedures. The authors report their experience using a new acellular porcine dermal graft (Enduragen) in 129 eyelids.

Ratings for 0% polished

(brown rice) were substantially l

Ratings for 0% polished

(brown rice) were substantially lower than those of 2.3% polished rice, which were intermediate in ratings between 0% and 4.4% polishing. However, most of the consumers (93%) expressed a willingness to substitute brown or 2.3% polished rice, if affordable, after the taste tests and education on nutritional and health benefits of whole grains.\n\nConclusion: Though most consumers preferred polished white rice, education regarding health benefits may help this population switch to brown or undermilled rice. Cooking quality and appearance of the grains were perceived as the most important factors to consider when purchasing rice among Chennai urban adults.”
“Purpose: CD163 is a scavenger receptor which is exclusively expressed on monocytes/ macrophages and participates in modulation of inflammatory response. GSK3235025 solubility dmso We aimed to evaluate ex vivo production of soluble CD163 (sCD163) by peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (scleroderma, SSc).\n\nMaterial/ Methods: Concentration of sCD163 was measured by commercially available ELISA kit in the PBMC suparnates from 23 SSc patients and 16 age-and sex-matched healthy

controls (HC). Eighteen SSc patients were Androgen Receptor Antagonist subsequently followed for at least three years or until death whichever happened earlier. Disease progression was defined as death due to SSc-related FK866 clinical trial organ complication, development of a new or progression of pre-existing SSc-related organ involvement.\n\nResults: PBMC from SSc patients released significantly greater amounts of sCD163 as compared with HC

(p<0.05). No significant associations between release of sCD163 by PBMC and baseline clinical or laboratory parameters of the disease could be found. However, concentration of sCD163 in cell culture supernates was significantly higher in 6 SSc patients who experienced subsequent progression of the disease as compared with 12 SSc patients with stable disease course over a 3-year follow-up period (p<0.05).\n\nConclusions: We show, for the first time, that PBMC from SSc release significantly greater amounts of sCD163 than do PBMC from healthy subjects. Evaluation of sCD163 production by PBMC ex vivo may serve as a new biomarker of disease progression. Further studies are required to evaluate the role of sCD163 in the development of SSc.”
“Following brain injury, return of consciousness and cough reflex are presumed to be associated with safe airway. We describe two patients who had a normal cough reflex, but impaired swallowing, which led to prolonged hospital stay. This report highlights the dissociation between the cough reflex and swallowing function in such patients.”
“Management of venous thromboembolism disease could be improved by new drugs with lower risk of bleeding and without the need of regular monitoring of anticoagulant effect.

Till today, researchers are mainly focused on use of EC systems i

Till today, researchers are mainly focused on use of EC systems in

batch processes. Looking to large quantities of wastewater from textile Industry, continuous flow regime may offer a better solution. Firstly, the operational parameters including current density (i), detention time (DT) and time of electrolysis were optimized. Then, total electric work (E) and sacrificial weight of anode were calculated under optimum conditions. The size of electrode plate (5cm*5cm*0.5cm, 124cm(2)) was kept constant for all sets of experiments. Our results indicated that for a solution of 300mg/L basic red dye 5001 B, almost 76% Elafibranor COD and 95% color were removed, when the pH was about 9, the DT was 20 min and the j was 14-17 mA/cm(2). Pseudo steady-state was achieved after passing 60 minutes of current

in the solution. In addition, the result of our study indicates that when the j and DT was increased above optimum level, charge reversal and surface saturation was occur due to the excessive addition of coagulant.”
“The Daporinad chemical structure columnar organization is most apparent in the whisker barrel cortex but seems less apparent in the gustatory insular cortex. We addressed here whether there are any differences between the two cortices in columnar information processing by comparing the spatiotemporal patterns of excitation spread in the two cortices using voltage-sensitive dye imaging. In contrast to the well known excitation spread in the horizontal direction in layer II/III induced in the barrel cortex by layer IV stimulation, the excitation caused in the insular cortex by stimulation of layer IV

spread bidirectionally in the vertical direction into layers II/III and V/VI, displaying a columnar image pattern. Bicuculline or picrotoxin markedly extended the horizontal excitation spread in layer II/III in the barrel cortex, leading to a generation of excitation in the underlying layer V/VI, whereas those markedly increased the amplitude of optical responses throughout the whole column in the insular cortex, subsequently Ispinesib supplier widening the columnar image pattern. Such synchronous activities as revealed by the horizontal and vertical excitation spreads were consistently induced in the barrel and insular cortices, respectively, even by stimulation of different layers with varying intensities. Thus, a unique functional column existed in the insular cortex, in which intracolumnar communication between the superficial and deep layers was prominent, and GABA(A) action is involved in the inhibition of the intracolumnar communication in contrast to its involvement in intercolumnar lateral inhibition in the barrel cortex. These results suggest that the columnar information processing may not be universal across the different cortical areas.”
“Objective: Optimal selection of a revascularization strategy in femoropopliteal occlusive disease (FPOD) remains controversial. Among endovascular treatment options for FPOD, covered stent placement has become increasingly used.

In this article, the authors review the state of the knowledge re

In this article, the authors review the state of the knowledge regarding these issues and nonpharmacologic and pharmacologic interventions for CRF. Physical activity and psychosocial interventions are recommended for practice. Numerous limitations find more of past studies need to be considered in the design of future studies. CRF is prevalent in preoperative, postoperative, and ongoing surveillance phases. Throughout the continuum of care for women with

breast cancer, clinicians must screen, further assess as indicated, and treat CRF, because it is associated with emotional distress and limits function and willingness to exercise. Cancer 2012;118(8 suppl):. (c) 2012 American Cancer Society.”
“Objectives\n\nThis paper aims to evaluate the internal and external responsiveness of the patient self-report questionnaires, comparatively to the traditional composite indices to assess the activity of rheumatoid arthritis (RA) in everyday practice.\n\nMethods\n\nOne hundred and ninety-one RA out-patients completed the clinical

arthritis activity (PRO-CLARA) index, the rheumatoid arthritis disease activity index (RADAI), the routine assessment of patient index data (RAPID3), and the patient activity score (PAS). Simultaneously, the disease activity score-28 joints based on CRP (DAS28-CRP) and ESR (DAS28-ESR), the simplified disease activity index (SDAI), the clinical disease activity LY2835219 clinical trial index (CDAI), and the mean overall index for RA (MOI-RA) were computed for each patient. Sensitivity to change was assessed after 6 months of treatment with disease-modifying anti-rheumatic drugs or biologics. Internal responsiveness was evaluated with the effect size (ES) and standardised response mean (SRM). External responsiveness was investigated by receiver operating characteristic (ROC), in categories of respondents, stratified

according to the response on an item on change in overall health. In addition, change scores were compared by calculating PCI-32765 solubility dmso correlation coefficients.\n\nResults\n\nNo significant differences in internal and external responsiveness were found between self-report questionnaires and composite indices. The internal responsiveness of the self-report questionnaires and composite measures was wide, with SRM and ES ranging from 1.03 (RADAI) to 1.80 (DAS28-ESR) and higher than that of the each individual measures. The responsiveness of the PRO-CLARA was equal to the DAS28-ESR, DAS28-CRP, SDAI or MOI-RA, but better than the CDAI.\n\nThe RADAI and PAS were less responsive than the PRO-CLARA and RAPID3. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator composite indices. The score changes of all combinations were highly correlated (p<0.0001).

In 232 of the 256 patients (90 6%), the injection was deemed to h

In 232 of the 256 patients (90.6%), the injection was deemed to have reached the glenohumeral joint, and these cases were

considered successful. Among these patients, the contrast medium was shown only in the joint in 189 (73.8%), Mcl-1 apoptosis whereas in 43 (16.8%) it was shown both in and out of the joint. Of the 24 misguided injections, 15 (5.9%) had anterior placement, 6 (2.3%) had posterior placement, and 2 (0.8%) had superior placement, whereas the material was located in all portions outside the joint in 1 (0.4%). Conclusions: This study showed that our modified anterior approach had an accuracy greater than 90% for the intra-articular injection of the glenohumeral joint without radiographic guidance. Level of Evidence: Level I, testing of previously developed diagnostic criteria in a series of consecutive patients with universally applied reference gold standard.”
“Background:This study sought to assess the feasibility of conducting a phase III HIV prevention trial using a multivalent human papillomavirus (HPV) vaccine (Gardasil; Merck, Whitehouse Station, NJ).Methods:A total of 479 sexually active women aged 16-24 years in the Western Cape, South Africa, were enrolled in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) Trial. Of these, 402 were HIV negative, nonpregnant, and randomized 1:1 to receive Gardasil

or a saline placebo vaccine. Vaccine doses were administered at enrollment, month 2, and month 6, and participants were followed for 1 month after the third dose. Enrollment HIV, HPV, other sexually transmitted infections (STIs), and cervical cytology were evaluated. Rates of accrual, vaccine compliance, GDC-0994 price and BEZ235 manufacturer adherence to protocol were monitored.Results:High rates of accrual of eligible females to study (93%) and completion of the 3-dose vaccine series (91%) were noted, with few protocol violations. Ineligibility due to reported HIV positivity was 19%, and another 12% of those enrolled tested HIV positive. STI prevalence was high, with 6.2%, 10.9%, and 32.8% testing positive for syphilis, gonorrhea, and chlamydia, respectively. Cervical prevalence of 1 of 37 HPV

types was 71%. STI and HPV prevalence was highest among the youngest women ( smaller than 19 years).Conclusions:Feasibility (successful accrual, retention, and vaccination) of conducting randomized placebo-controlled trials of HPV vaccines among HIV high-risk women in South Africa was demonstrated. This work demonstrates that phase III HIV prevention trials need to intervene at young ages and screen and treat multiple STIs concurrently to have a measurable impact on HIV acquisition.”
“Mycoreovirus 1 (MyRV1) has 11 double-stranded RNA genome segments (S1 to S11) and confers hypovirulence to the chestnut blight fungus, Cryphonectria parasitica. MyRV1 genome rearrangements are frequently generated by a multifunctional protein, p29, encoded by a positive-strand RNA virus, Cryphonectria hypovirus 1. One of its functional roles is RNA silencing suppression.

When overexpressed in a tetracycline (Tet)-based protein chase mo

When overexpressed in a tetracycline (Tet)-based protein chase model, constitutive heat shock cognate 70 (Hsc70) and inducible Hsp72 slowed or accelerated tau clearance, respectively. Tau synergized with Hsc70, but not Hsp72, to promote microtubule assembly at nearly twice the rate of either PHA-739358 research buy Hsp70 homologue in reconstituted, ATP-regenerating Xenopus extracts supplemented with rhodamine-labeled tubulin and human recombinant Hsp72 and Hsc70. Nuclear magnetic resonance spectroscopy with human recombinant protein revealed that Hsp72 had greater affinity for tau than Hsc70 (I/I-0 ratio

difference of 0.3), but Hsc70 was 30 times more abundant than Hsp72 in human and mouse brain tissue. This indicates that the predominant Hsp70 variant

in the brain is Hsc70, suggesting that the brain environment primarily supports slower tau clearance. Despite its capacity to clear tau, Hsp72 was not induced in the Alzheimer’s disease brain, suggesting a mechanism for age-associated onset of the disease. Through the use of chimeras that blended the domains of Hsp72 and Hsc70, we determined that the reason for these differences between Hsc70 and Hsp72 with regard to tau clearance kinetics lies within their C-terminal domains, which are essential for their interactions PFTα cell line with substrates and cochaperones. Hsp72 but not Hsc70 in the presence of tau was able to recruit the cochaperone ubiquitin ligase CHIP, which is known to facilitate the ubiquitination of tau, describing a possible mechanism of how the C-termini of these homologous Hsp70 variants can differentially regulate tau triage. Thus, efforts to promote Hsp72 expression and inhibit Hsc70 could be therapeutically relevant for tauopathies.-Jinwal, U. K., Akoury, E., Abisambra, J. F., O’Leary, J. C., III,

Thompson, A. D., Blair, L. J., Jin, Y., Bacon, J., Nordhues, B. A., Cockman, M., Zhang, J., Li, P., Zhang, B., Borysov, S., Uversky, V. N., Biernat, J., Mandelkow, E., Gestwicki, J. E., Zweckstetter, M., Dickey, C. A. Imbalance of Hsp70 family variants fosters tau accumulation. FASEB J. 27, 1450-1459 (2013). www.fasebj.org”
“Vanadium compounds are promising agents in the therapeutic treatment JQ-EZ-05 Epigenetics inhibitor of diabetes mellitus, but their mechanism of action has not been fully elucidated. The current work investigated the effects of vanadyl acetylacetonate, VO(acac)(2), on peroxisome-proliferator-activated receptor gamma (PPAR gamma) and adiponectin, which are important targets of antidiabetic drugs. The experimental results revealed that vanadyl complexes increased the expression and multimerization of adiponectin in differentiated rat adipocytes. VO(acac)(2) caused activation of p38 mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) and elevation of PPAR gamma levels.

In right-sided curve, the risks of the aorta impingement were mai

In right-sided curve, the risks of the aorta impingement were mainly from left PS while in left-sided

curves, from right PS. The aorta was more proximal to entry points in right-sided lumbar curve when compared with left-sided curve; thus placing PS carries more risks in right-sided thoracolumbar/lumbar curve. Surgeons should be more cautious when placing PSs on the concave sides of T12 and L1 vertebrae of right-sided thoracolumbar/lumbar curves.”
“The phenomenon of peak area decrease due to high injection voltage (V-inj, e.g. 10-30 kV, 200-600 V/cm in the 50 cm capillary) was found in the analysis of very dilute DNA fragments ( smaller than 0.2 mg/L) by using high-sensitive electrokinetic supercharging-CGE. The possibility of DNA cleavage in aqueous solution PXD101 mouse was suggested, in addition to the aggregation phenomenon that is already known. The analysis of intentionally voltage-affected fragments (at 200 V/cm) also showed decreased peak areas depending on the time of the voltage BMN-673 being applied. Computer simulation suggested that a high electric field (a few kV/cm or more) could be generated partly between the electrode and the capillary end during electrokinetic injection

(EKI) process. After thorough experimental verification, it was found that the factors affecting the damage during EKI were the magnitude of electric field, the distance between tips of electrode and capillary (D-e/c), sample concentration and traveling time during EKI in sample vials. Furthermore, these factors are correlating with each other. A low conductivity of diluted sample would cause a high electric field (over a few hundred volts per centimeter), while the longer D-e/c results in a longer traveling time during EKI, which may cause a larger degree of damage (aggregation selleck inhibitor and cleavage) on the DNA fragments. As an important practical implication of this study,

when the dilute DNA fragments (sub mg/L) are to be analyzed by CGE using EKI, injection voltage should be kept as low as possible.”
“The targeting of proteins to subcellular organelles is specified by the presence of signal/leader peptide sequences normally located on the N-terminus. In the past two decades, messenger RNA (mRNA) localization, a pathway driven by cis-acting localization elements within the RNA sequence, has emerged as an alternative mechanism for protein targeting to specific locations in the cytoplasm, on the endoplasmic reticulum or to mitochondria and chloroplasts. In this review, we will summarize studies on mRNA-based protein targeting to the endoplasmic reticulum and chloroplast within plant cells.”
“Serelaxin, a recombinant form of the human relaxin-2 hormone, is currently under clinical investigation for treatment of acute heart failure.

Here, we show that the acute deletion of caspase-8 in the gut of

Here, we show that the acute deletion of caspase-8 in the gut of adult mice induces enterocyte death, disruption of tissue homeostasis, and inflammation, check details resulting in sepsis and mortality. Likewise, acute deletion of caspase-8 in a focal region of the skin induces local keratinocyte death, tissue disruption, and inflammation. Strikingly, RIPK3 ablation rescues both phenotypes. However, acute loss of cFLIP in the skin produces a similar phenotype that is not rescued by RIPK3 ablation. TNF neutralization protects from either

acute loss of caspase-8 or cFLIP. These results demonstrate that caspase-8-mediated suppression of RIPK3-induced death is required not only during development but also for adult homeostasis. Furthermore, RIPK3-dependent HSP signaling pathway inflammation is dispensable for the skin phenotype.”
“Very little is known about the combined effects of low doses of heavy metals and radiation. However, such “multiple stressor” exposure is the reality in the environment. In the work reported in this paper, fish were exposed to cobalt 60 gamma irradiation with or without copper or aluminum in the water.

Doses of radiation ranged from 4 to 75 mGy delivered over 48 or 6 h. Copper doses ranged from 10 to 80 mu g/L for the same time period. The aluminum dose was 250 mu g/L. Gills and skin were removed from the fish after exposure and explanted in tissue culture flasks for investigation of bystander effects of the exposures using a stress signal reporter assay, which has been demonstrated to be a sensitive indicator of homeostatic perturbations in HSP990 cells. The results show complex synergistic interactions of radiation and copper. Gills on the whole produce more

toxic bystander signals than skin, but the additivity scores show highly variable results which depend on dose and time of exposure. The impacts of low doses of copper and low doses of radiation are greater than additive, medium levels of copper alone have a similar level of effect of bystander signal toxicity to the low dose. The addition of radiation stress, however, produces clear protective effects in the reporters treated with skin-derived medium. Gill-derived medium from the same fish did not show protective effects. Radiation exposure in the presence of 80 mu g/L led to highly variable results, which due to animal variation were not significantly different from the effect of copper alone. The results are stressor type, stressor concentration and time dependent. Clearly co-exposure to radiation and heavy metals does not always lead to simple additive effects.”
“Vehicle density is one of the main metrics used for assessing road traffic condition. High vehicle density indicates that traffic is congested.

Here, we discuss the roles of integrins in modulating cellular re

Here, we discuss the roles of integrins in modulating cellular responses to a changing ECM, in particular the regulation of survival and invasion among invasive endothelial cells.”
“As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal

diseases. Over 1000 publications were reviewed for 2008 and DNA Damage inhibitor 2009, and the important advances in basic science as well as clinical applications were considered. In Part I of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption;

necrotizing enterocolitis; and immunology/allergy. These topics were Selleck Panobinostat chosen because of their importance to the practicing physician. (C) 2012 Baishideng. All rights reserved.”
“The purpose of this work was to develop a PCR method for the identification of smoked paprika “Pimenton de la Vera” adulteration with paprika elaborated from varieties of pepper foreign to the la Vera region, in central western Spain. Three autochthonous varieties of pepper, Jaranda, Jariza, and Bola, and the varieties Papri Queen, Papri King, Sonora, PS9794, and Papri Ace, foreign to the La Vera region, were used in the study. Analyses of the ITS and 5.8S rDNA, RAPD-PCR, SSR, and ISSR were tested. RAPD-PCR, SSR, and ISSR analyses allowed differentiation among the varieties of paprika analyzed. There was no difference in the sequence of ITS1-5.8S rDNA-ITS2. In addition, with the RAPD-PCR primers S13 and S22, two molecular markers were obtained of 641 and 704 bp, respectively, which allowed all of the smoked paprika varieties to be differentiated from paprikas elaborated with the five foreign varieties. These two molecular markers Fludarabine solubility dmso were investigated as

a basis for detecting the adulteration of smoked paprika with paprika elaborated from foreign varieties of pepper.”
“Introduction: Increased understanding in intracellular signaling pathways leading to carcinogenesis, proliferation, migration, invasion, angiogenesis, and anti-apoptosis of colorectal cancer cells has been critical for target identification and drug development. Specific protein kinase inhibitors (KIs) have been developed to block activated pathways associated with tumor growth and progression. Although showing promising activity in preclinical models, until now, the majority of KIs were not able to demonstrate clinically meaningful efficacy in Phase II/III trials.\n\nAreas covered: The major pathways altered in colorectal cancer will be highlighted, and molecularly defined targets will be discussed. The mechanisms of action and the proof of principle demonstrated in preclinical models of KIs and the disappointing efficacy in clinical trials will be reviewed.