Thus, urges do not occur in isolation, but are immediately incorp

Thus, urges do not occur in isolation, but are immediately incorporated into an existing homeostatic cognitive and affective system of the individual. For example, self-efficacy, ie, the confidence in being able to resist the urge,

can profoundly modulate drug use behavior.49 Moreover, temptation, ie, the contextual characteristics that are aimed to increase desire, leads to stronger urges to drink alcohol, greater difficulty controlling urges, and increased alcohol consumption, even Inhibitors,research,lifescience,medical when controlling for alcohol consumption in the past month.50 Finally, social stress frequently occurs before, and may contribute to the degree of, cravings.51 Substance -using individuals who perceive an opportunity to consume their drug of choice report higher urges than those who do not anticipate being able to use the drug.52 It has been argued that the degree of urge modulates Inhibitors,research,lifescience,medical the threshold for triggering an action.53 Therefore, craving and urges are important component processes of decision-making in the presence of ambivalence or conflict.54 Thus, similarly to the hedonic properties of a reward processing, the incentive motivational

aspects are an Inhibitors,research,lifescience,medical emerging property based on the stimulus characteristics and the individuals homeostatic state. One way to study the neural substrates underlying urges is to selleck products examine frequently observed behaviors that are often attributed Inhibitors,research,lifescience,medical to urge-related processing. Here, four examples of urge-related behaviors are reviewed that can shed new light on the neurobiology of these metacognitive states. First, in a functional positron emission tomography (PET) study to investigate the neural substrates underlying

itch and the motor intention of the urge to scratch, investigators found activation of the anterior cingulate cortex, supplementary motor area, premotor area, and inferior parietal lobule.55 Others have observed that increases in regional cerebral blood flow in orbitofrontal cortex, neostriatum, global pallidus, and thalamus were related to urges to perform compulsive movements.56 medroxyprogesterone A functional Inhibitors,research,lifescience,medical magnetic resonance imaging (fMRI) study of intense itch and urge to scratch showed significant activity in the genual anterior cingulate, striatum, and thalamus as well as orbitofrontal, supplementary motor, posterior parietal areas, and bilateral insula.57 Second, air hunger, ie, the uncomfortable urge to breathe, is another urge-related phenomenon, which can be used to study the neural systems underlying urge and craving. Several neuroimaging studies have found activation of limbic and paralimbic regions during air hunger, which are often found to modulate homeostatic imbalance such as pain, thirst, and hunger for food. A recent fMRI study found that anterior cingulate, operculum, cerebellum, amygdala, thalamus, and basal ganglia were activated during air hunger.

This study also identifies that when participants are managing to

This study also identifies that when participants are managing to return to their premorbid walking aid, it does not always mean that it has been done so appropriately and safely. What is most concerning is that the population studied was already at a high risk of falls, with all participants having sustained a fall related fracture, and inappropriate walking aid selection, and Libraries incorrect

walking aid use, may lead to an increased risk of falls (Bateni and Maki 2005, Campbell et al 1981, Charron et al 1995, Graafmans et al 2003, Koval et al 1995, Liu et al 2009, Mahoney et al 1994). The strict exclusion criteria of the INTERACTIVE trial meant that only 23% of all patients admitted to the recruitment sites were eligible for participation in the study. The main reason for exclusion from this study was residence in an aged care facility, thus the results are not generalisable to those settings. However, the authors believe that the findings are applicable to older people who live in community settings following hip fracture. Of the 23% who were eligible, 56% did consent, meaning that even if those participants who did not consent had perfect walking aid prescription, a substantial proportion of the cohort

would still have been using an inappropriate aid, putting them at risk. The see more results suggest that scheduling of formal follow up by a physiotherapist might be appropriate for hip fracture patients on discharge from hospital. A high proportion of participants (32%) were observed not only to make inappropriate choices of walking aid, but also to use the walking also aid in an unsafe manner. The nature of misuse of walking aids observed in the study (ie, inappropriate aids or inappropriate non-use of aids) could be expected to further compromise balance and increase the potential for

falls. Participants often assumed inaccurately that, because hired equipment had a specified loan period, this directly correlated with the amount of time that they would be required to use the walking aid. When participants could remember goals that had been specified by the physiotherapist, the goals were non-specific and relied on judgments about safety, which may have been difficult for patients to make without discussion with a physiotherapist, eg, ‘use until safe to trial a walking stick’ or ‘use until able to walk unaided’. When participants made the decision to change their walking aid, it was often not on the advice of a physiotherapist and in most instances was based on their own opinions. Social stigmas attached to ageing, disability, and medical device use may have powerful influences on older persons’ decisions to accept or reject mobility aids (Liu et al 2009). Self-made decisions about walking aid use may be heavily influenced by factors other than physical needs.

5 1 pH-Sensitive PEG Release While normal tissues and blood have

5.1. pH-Sensitive PEG Release While normal tissues and blood have a physiological pH near 7.4, human tumors have lower pH values (~6.0/6.5) because of an elevated rate of glycolysis [275, 276]. pH-sensitive bonds have been developed for the coupling of PEG to liposomes [277] (Figure 1). pH-sensitive liposomes achieved

a higher concentration Inhibitors,research,lifescience,medical of cargo in the cytoplasm and nucleus than non-pH-sensitive PEGylated liposomes in vitro and allowed faster intratumoral content release in vivo [278, 279]. In addition to tumor sensitivity, pH sensitive BIBF 1120 manufacturer groups can potentiate the efficacy of targeted drug-loaded liposomes. Folate-targeting of daunorubicin-loaded liposomes by incorporation of a pH-sensitive folate-PEG-cholesterol hemisuccinate (CHEMS) conjugate combined tumor targeting and increased Inhibitors,research,lifescience,medical drug release at the tumor site with improved chemotherapeutic activity over untargeted liposomes [280]. Similarly, untargeted cisplatin-loaded liposomes or EGFR-targeted gemcitabine-loaded liposomes incorporating CHEMS had superior antitumor activity over untargeted drug-loaded liposomes or free drugs [281, 282]. Obata et al. used a

glutamic acid-based zwitterionic lipid (1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate) as titratable lipid for doxorubicin delivery [283]. These liposomes showed a charge inversion from negative to positive at acidic Inhibitors,research,lifescience,medical pH with endosomal escape leading to higher doxorubicin delivery in the cytoplasm and higher toxicity in vitro over conventional liposomes. This resulted in superior antitumor activity in vivo. Biswas et al. developed a new pH-sensitive DSPE-PEG-hydrazone-PEG2000 conjugate for attachment of ligands to the liposome surface Inhibitors,research,lifescience,medical [284]. In their work, the cell penetrating peptide (TATp) was unmasked after PEG release at acidic pH allowing efficient cellular uptake. Recently, three Inhibitors,research,lifescience,medical new approaches for generation of pH sensitivity have been reported. First, by electrostatic adsorption

of negatively charged carboxyl-modified gold nanoparticles to the surface of cationic liposomes (egg dipalmitoylphosphatidylcholine/DOTAP 9:1 weight ratio) at pH 7 (pKa of 5 for the carboxylic below group) [285]. Authors reported detachment of gold nanoparticles at acidic pH due to protonation of the carboxyl groups and speculated that a similar strategy could be applied with negative charged liposomes and amine-modified gold nanoparticles. Second, a platform for finely tuned pH-induced PEG release was introduced using phenyl-substituted-vinyl-ether-(PIVE)-PEG lipid conjugates [286]. Liposomes containing PIVE showed pH-induced dePEGylation and content release at acidic pH whereas they were stable at physiological pH. Third, ligand unmasking by acidic pH-induced membrane reorganization has been introduced as a reversible ligand-masking strategy.

Confirmation was made using the GC-MS technique, and isolation wa

Confirmation was made using the GC-MS technique, and isolation was done using a preparative HPLC, equipped with an aliquots collector. The microdilution broth susceptibility assay was utilized to determine minimum inhibitory concentrations (MICs). Results: Our in vitro study demonstrated the antibacterial activity

of the Thymus syriacus Boiss essential oil and its components against the tested isolates at levels between 0.375 and 50 µl/ml. The main components of the T. syriacus essential oil were carvacrol, γ-terpinene, and ß–caryophyllene. MIC90 values for the T. syriacus essential oil against the gram-negative organisms varied between 3.125 and Inhibitors,research,lifescience,medical 12.5 µl/ml. The most effective components against the gram-negative bacteria were thymol, carvacrol, dihydro-carvon, and linalool respectively. Conclusions: The T. syriacus essential oil and some of its components exhibited very good inhibitory effects Inhibitors,research,lifescience,medical against Syrian gram-negative isolates. Key Words: Essential oils, Gram-negative bacteria, Minimum inhibitory concentration Introduction Safety testing on essential oils, when used as directed, shows very few bad side effects or risks. Some essential oils have Inhibitors,research,lifescience,medical been approved as ingredients in food and are classified and generally recognized as safe.1 Essential oils should be regarded as one of the several available

feed additives that have been demonstrated to have antibacterial activity against undesirable pathogenic bacteria such as Salmonella spp.2 Essential oils consist of a number of active Inhibitors,research,lifescience,medical compounds, some of them comprising more than 60 individual components that can inhibit the growth of certain microorganisms.3 Besides flavoring, aromatic plants have been drawn upon for their medicinal properties for Inhibitors,research,lifescience,medical centuries.4 As natural products with well-documented

and repeatedly demonstrated efficiency against a wide range of microorganisms, essential oils receive particular attention as agents suitable for prophylactic and medical treatment.5 Many essential oil isolates exhibit inhibitory Bumetanide properties in challenge tests against microorganisms.6 Herbs have been found to possess antimicrobial activity and anti-viral properties.7 The genus Thymus (Bosutinib molecular weight Lamiaceae) consists of more than 300 evergreen species of herbaceous perennials and sub shrubs, native to Southern Europe and Asia.8 This genus is represented by 38 species and altogether 64 taxa.9 The Thymus genus species (Lamiaceae) are well known in Syria, where their common name is Zattar.10 They are native plants and can be found wildly or cultivated in most Syrian provinces, especially in the north-west, coastal, and south-west regions. Five species of Thymus are found in Syria. Thymus syriacus Boiss are used as herbal tea and condiments. Fresh leaves are used for aromatization of home-made jams, candies, and similar confections.

0×104 (J/mol), , AEn = −5 866729×104, The factor [CB]/[CB0] co

0×104 (J/mol), , AEn = −5.866729×104, . The factor [CB]/[CB0] corrects LEnmax for changes of [CB]; the second factor is introduced to damp changes of [CB]. KBref is not constant, but depends on [Ca2+]. The stroke generating fluxes are given by: (A15a) (A15b) Both fluxes are identical as long as uncoupling is absent. The first factor corrects LStrmax = 4.6 × 10−4 (µM/ms)×(mol/J) for changes of [CBt] – [CB]. The second factor introduces [Ca2+] dependence of LStr. The third factor is responsible for the hyperbolic character

of the flux equation at constant [Ca2+] with KICB = −1.8 × 104 J/mol, which learn more represents the inhibition constant, KRref = 1.310889 × 10−4. Inhibitors,research,lifescience,medical λ values are not independent; this interdependency is given in Results. Uncoupling is formulated to occur in two steps, expressed by λStr1P = 0.15 and λStr2P = 0.85. SIMGLYgen (A16) . . . . . . . . . . . . . The above set of differential equations without a variable [Mg2+] ([Mg2+] = 0.8 mM = const.) is used to calculate the various Inhibitors,research,lifescience,medical points of figures (Figure 1B, Figure 2, Figure 3, and Figure 4) for a given [Ca2+] and various loads. As already mentioned, [Mg2+] is introduced as a variable only for conditions of very high power output leading to fatigue. From the output of the simulation many more variables, as shown here, can be obtained as functions

of time, Inhibitors,research,lifescience,medical which may often be helpful in understanding underlying mechanisms.
How topology shapes dynamics is a long-standing question in the field of network theory [1,2]. Many attempts have been formulated Inhibitors,research,lifescience,medical to understand the functional structure of metabolic networks from first principles using evolutionary, biochemical, or graph theoretical arguments [3,4,5,6,7,8]. Several works have argued that the network topology of metabolic systems is markedly optimized for robustness. For example, Marr et al. [9] used binary dynamic probes to demonstrate that on average fluctuations are dampened out in real metabolic networks.

Also, there seems to be a selection for minimal metabolic pathways, given the experimental conditions [10]. The accessible nutrients for a species may thus be inferred by analyzing the network topologies. Inhibitors,research,lifescience,medical Furthermore, robustness Dipeptidyl peptidase of metabolism against gene or reaction deletions has been explored using flux-balance analysis (FBA) [11]. Particularly, its capacity to predict gene essentiality with high accuracy for E. coli and Saccharomyces cerevisiae has turned FBA into a widely accepted method for in silico studies of metabolic states [12,13]. More recent refinements of FBA focus on the redistribution of fluxes due to gene deletions [14,15]. Along similar lines of research, metabolic reactions have been classified in several ways based on topological information [3,16,17,18]. Here we will focus on two recent examples providing such classifications: UPUC (uniquely producing/consuming) and SA (synthetic accessibility) reactions. UPUC metabolites have been introduced by Samal et al. [19].

These crystallographic studies have been complemented by ultrastr

These crystallographic studies have been inhibitors complemented by ultrastructural studies of virions using negative stain electron microscopy and more recently by cryomicroscopy of frozen-hydrated specimens that preserves native structure. Electron cryotomography provides a further advance

in our understanding of influenza virus ultrastructure by reconstructing three-dimensional maps of the frozen-hydrated specimen [4] and [5]. The resulting reconstructions are at considerably lower resolution than X-ray crystal structures because of radiation damage due to the requirement of recording many images of the same specimen. Furthermore, limited tilt angles cause blurring in one direction. Therefore interpretation and modeling must take into account the anisotropic resolution of the maps. Nevertheless, the interpretation of three-dimensional maps with X-ray structures Pexidartinib datasheet creates a molecular model of virus architecture. Here we describe three-dimensional maps of A/Aichi/68 X-31 and A/Udorn/72 virions determined by electron cryotomography. The latter strain maintains a filamentous phenotype in the laboratory and displays a structural regularity that may be exploited for structural study [4] and [6]. We build a model for the virus surface glycoproteins by placing X-ray

models for the HA ectodomain at glycoprotein positions in the map. The models define structural parameters for the virus that have important consequences for understanding viral infection and the host immune response. Growth, purification, and cryotomography of A/Udorn/72 and A/Aichi/68 X-31 virus MLN8237 mouse were done as previously described [4]. Structural models of the virus envelope were constructed by selecting cylindrical regions of virions and placing the X-ray models (pdb id 1HGE) into spike density perpendicular to the surface. Intermolecular distances were calculated between the centers-of-mass of the HA models (78 Å from membrane). For studies of FI6 Fab binding [7], the model (pdb id 3ZTJ) below with different numbers of Fabs bound was examined

for overlap with other HA models. To measure the relative distance of receptor binding sites, the O2 position of the sialic acid in the receptor-binding site was determined for all HA coordinates built on the virus surface. Cryotomography was used to study the three-dimensional structure of frozen-hydrated influenza virions (H3N2). Udorn virions typically show a capsular (cylindrical with hemispherical caps at the ends) or filamentous morphology. Fig. 1a shows a tomogram slice of a capsule-shaped Udorn virion with its long axis lying in the plane of the ice film. RNPs run the length of the virion inside the lipid bilayer, which is lined on the inside with a layer of the M1 protein, and on the outside by glycoprotein spikes.

In a double-blind, placebo-controlled, parallel-group study in 30

In a double-blind, placebo-controlled, parallel-group study in 30 healthy volunteers treated with 1 mg alprazolam 1 hour prior to a 50-μg CCK-4 challenge, a significant reduction of API and PSS scores

and of the number of reported symptoms compared to placebo pretreatment were found.49 A recent study (following an unbalanced, three-arm, two-period, crossover, double-blind, placebo-controlled design) in 21 male volunteers Inhibitors,research,lifescience,medical who received 1 mg of lorazepam 2 hours before CCK-4 did not show an attenuated panic signal in any PSS parameter.50 However, this dose of lorazepam was considerably lower than in the two previous studies reported above. Concerning Inhibitors,research,lifescience,medical anti-panic non-selective Epigenetics inhibitor serotonin reuptake inhibitors (imipramine or clomipramine) no study on CCK-4 panic in healthy volunteers has been published. With an SSRI, Kellner

et al51 could not demonstrate an inhibitory effect of escitalopram (6 weeks of 10 mg/d) on a 50-μg CCK-4 challenge in a double-blind, placebo-controlled, randomized, within-subject crossover design in 30 healthy young men. Induced panic under escitalopram was even significantly more pronounced in the subgroup of subjects with the short/short genotype for the serotonin transporter Inhibitors,research,lifescience,medical linked polymorphic Inhibitors,research,lifescience,medical region in this study. Another investigation with an identical dose and duration of escitalopram pretreatment also failed to show a significant inhibitory effect on CCK-4 panic in healthy man (I. Tőru, personal communication). Investigational anti-panic drugs and CCK-4 panic in healthy volunteers To test the effectiveness of a single oral 100 mg dose of the cholecystokinin

B antagonist CI-988 in attenuating panic symptoms induced by CCK-4 a randomized, placebo-controlled, double-blind, three-way crossover design was used in 30 healthy Inhibitors,research,lifescience,medical men.52 A small (14%), but significant decrease of sum intensity scores of panic symptoms was observed under CI-988. However, there was no marked difference in the number of panic symptoms. In contrast, a subsequent study in 14 patients with panic disorder who were given 50 also or 100 mg of CI-988 in a double-blind, two-period incomplete block design 2 hours before injection of CCK-4 failed to show a statistically significant treatment effect on the total intensity score on the PSS (the primary efficacy parameter), as well as on the number of panic symptoms, time to and occurrence of the first panic symptoms, duration of symptoms, intensity of apprehension, and the percentage of patients who did not have a panic attack.

Of all the available materials, calcium phosphate was selected as

Of all the available materials, calcium phosphate was selected as core of choice as it is ceramic (structurally most regular materials) and crystalline in nature (high degree of order). The surface exhibits high level of surface energy which favors the binding

of carbohydrate on surface film. C59 wnt molecular weight In the second step, extent of sugar loading was quantified by using anthrone method. The method is based on hydrolysis of carbohydrates to simple sugars in presence of acid followed by dehydration of sugars to furfural derivatives, e.g. hydroxyl methyl furfural. Furfural derivatives react with anthrone to form a deep green color with an absorption maximum at 625 nm. The sugar adsorption on core was confirmed using FTIR spectroscopy. Further drug is adsorbed over sugar loaded core particles through non-covalent and ionic interactions. The pimozide loaded aquasomes exhibited

smaller particle size than that of pimozide pure drug. Hence it can be concluded that, the aquasomal formulation had lead to reduction of particle size to nanometer range. Improved dissolution was observed with aquasome formulation of pimozide than that of pure drug, which can be accounted for nanosize and aqueous environment of the aquasomes. The release followed the first order kinetics which supported the mechanism of immediate release of pimozide. Ceramic nanoparticles were developed as a technological innovation for the pimozide delivery via the peroral route. Co-precipitation by sonication technique NVP-BGJ398 ic50 was found to give more yield

than other methods. Size analysis indicated spherical particles in the size range of aquasomes. Release studies of aquasomes showed greater dissolution than that of pure drug. Thus aquasomes can be used for enhancing the solubility of poorly soluble drugs. All authors have none to declare. Authors would like to express thanks to Vasudha Pharma Chemical Ltd, Hyderabad for providing the Sclareol pimozide gift sample. Authors would also like to express their thanks to Dr Sathesh, HOD, Pharmaceutics for his guidance and support. “
“The physiological environment within a living organism is mostly chiral. inhibitors Therefore, chiral discrimination has been an issue in the development and use of pharmaceutical drugs. Enantiomers of racemic drugs often differ in pharmacokinetic behavior or pharmacological action.1 In recent years, research has been intensified to understand the aspects of the molecular mechanism for stereoselective biological activities of the chiral molecules. The development of analytical methods for the assessment of enantiomeric purity is challenging due to the fact that enantiomers possess virtually identical properties.2 In the pharmaceutical industry, much emphasis is put on chiral analysis. The reason is the potentially different behavior of the enantiomers of a chiral drug molecule after administration.

However, it is important to emphasize that the evidence from this

However, it is important to emphasize that the evidence from this strongly supports the possibility that NAFLD could also be atherogenic among NAFLD patients without diabetes. Another limitation of this study was that the diagnosis of NAFLD was based on the exclusion

of known etiologic factors of Inhibitors,research,lifescience,medical liver disease and on US examination but was not confirmed by liver biopsy for ethical reasons. Thus, currently it is uncertain whether there is a significant association between early carotid atherosclerosis and the severity of liver histology among NAFLD patients. Clarification of this aspect may help to explain the Enzalutamide in vitro underlying mechanisms and may be of clinical importance in planning preventive and therapeutic strategies. However, US examination is by far the commonest way Inhibitors,research,lifescience,medical of diagnosing NAFLD in clinical practice19) and the presence of > 33% fat on liver biopsy was optimal for radiological detection of steatosis.34) Although US is Inhibitors,research,lifescience,medical highly operator-dependent, and the diagnosis of fatty liver is based mainly on the subjective assessment of liver echogenicity, the reliability of US for the detection of fatty liver showed kappa statistics ranging from

0.54 to 0.92 for intrarater reliability and from 0.44 to 1.00 for interrater reliability.35) In conclusion, NAFLD is significantly associated Inhibitors,research,lifescience,medical with carotid atherosclerosis in non-diabetic outpatients even without MetS. Carotid screening for NAFLD might be beneficial for assessment of future atherosclerotic complications, because NAFLD might be a marker of increased carotid IMT and of the presence of carotid plaque in outpatients undergoing abdominal US.
The analysis of mechanical dyssynchrony by echocardiography

Inhibitors,research,lifescience,medical has been widely adopted due to its advantages of being easily available, non-invasive, radiation free and rapid technological development. The techniques range from conventional M-mode and Doppler echocardiography to more advanced tissue Doppler imaging (TDI), three-dimensional (3D) echocardiography and two-dimensional speckle tracking imaging, and most recently, 3D speckle tracking imaging. The parameters of systolic ADP ribosylation factor dyssynchrony include those signify the dispersion of the time to peak ventricular contraction, as represented by the standard deviation or maximal delay among a certain amount of LV segments, and the difference between the LV and RV. The majority of them were derived from CRT trials with cutoff values to define dyssynchrony and therefore suggested by the American Society of Echocardiography in an expert consensus statement (Table 1).

22,23 Their subsequent development would lead to an apparent loca

22,23 Their subsequent development would lead to an apparent local recurrence that is simply the expression of the natural history of pre-existing lesions. Special care should be taken in glottic cancer with involvement of the anterior commissure or deep surgical margin.

Several articles have reported on lower local control rate Inhibitors,research,lifescience,medical in glottic cancer when involvement of the anterior commissure was found.24–29 The difficulty in adequate exposure of the anterior commissure using conventional laryngoscope can contribute to this result, stressing the importance of fully exposing this site during TLM by the use of larger and better designed laryngoscopes and by resection of supraglottic tissue as necessary.28,30 Anatomic constraints and hampered visibility may limit the surgeon’s ability Inhibitors,research,lifescience,medical to achieve adequate deep surgical margins. Peretti et al.,19 who evaluated the impact of superficial and deep positive margins in 595 patients treated with TLM for glottic cancer, found low impact of superficial positive margins on local control compared to deep infiltration (93% versus 85%). Transection

of the tumor can give the Inhibitors,research,lifescience,medical surgeon a much better assessment of the depth dimension and clear visualization of the deep margin during surgery.31 In order to ameliorate margin assessment different techniques have been studied. Frozen Section One of the valuable techniques is intraoperative resection margin evaluation by using a frozen section analysis for biopsy taken from the cut border of tissue remaining in the patient. Remacle et al.32 found frozen section to be reliable with 95% of the results accurate and stressed the possibility Inhibitors,research,lifescience,medical immediately to enlarge cordectomy to

obtain clear margin. Fang et al.17 reported that the status of the initial frozen-section margin analysis is a robust predictor of survival. In patients who had involvement by malignancy of the initial resection margin on frozen section, there was a statically significant increased rate of recurrent disease within the first year regardless of eventually Inhibitors,research,lifescience,medical achieving clear margins during the initial surgery. When using frozen section, one has to be familiar with its drawbacks. The reliability of a margin verdict using small fragments taken from the cut border PD184352 (CI-1040) of tissue remaining in the patient depends on the surgeon’s precision and the pathologist’s experience. Insufficient biopsy material or biopsy taken in between neoplastic cells can produce false negative results. Postoperative or post-radiotherapy patients can have granulation tissue, inflammatory click here infiltrate, or post-irradiation cell changes, making diagnosis more difficult. Moreover, use of multiple frozen sections for margin control, after the tumor has been removed, has intrinsic discrepancy with the phonomicrosurgical approach to the treatment of vocal cord cancer.