Salivary Biomarkers for Oral Cancer Detection: An Exploratory Systematic Review.

Different efforts have been made to find better and less invasive methods for the diagnosis and prediction of oral cancer, such as the study of saliva as a source of biomarkers. The aim of this study was to perform a scoping review about salivary molecules that have been assessed as possible biomarkers for the diagnosis of oral squamous cell carcinoma (OSCC). A search was conducted using EBSCO, PubMed (MEDLINE), Scopus, and Web of Science. The research question was as follows: which molecules present in saliva have utility to be used as biomarkers for the early detection of oral cancer? Sixty-two studies were included. Over 100 molecules were assessed. Most of the markers were oriented towards the early diagnosis of OSCC and were classified based on their ability for detecting OSCC and oral potentially malignant disorders (OPMDs), OSCC outcome prediction, and the prediction of the malignant transformation of OPMDs. TNF-α, IL-1ß, IL-6 IL-8, LDH, and MMP-9 were the most studied, with almost all studies reporting high sensitivity and specificity values. TNF-α, IL-1ß, IL-6 IL-8, LDH, and MMP-9 are the most promising salivary biomarkers. However, more studies with larger cohorts are needed before translating the use of these biomarkers to clinical settings.

Current and Future Perspectives of Microscopic and Endoscopic Transsphenoidal Surgery for Pituitary Adenomas: A Narrative Review.

Transsphenoidal resection remains the standard treatment for most pituitary adenomas. However, the ideal surgical approach to safely access these lesions, either microsurgical or endoscopic, continues to be debated. Since the introduction of endoscopic transsphenoidal surgery, centers around the world have increasingly adopted this technique, experiencing a shift away from the conventional microsurgical approach. Large series reporting the efficacy and safety of endoscopic surgery have fueled a growing interest in comparing clinical outcomes between both approaches. Still, proving superiority of either surgical approach remains an elusive task due to the inherent drawbacks of surgical observational studies, as we are still faced with a growing body of evidence reporting conflicting results. Thus, a comprehensive discussion regarding the reach and limitations of both techniques becomes necessary. In this narrative review, we perform a critical appraisal of the literature and provide an expert opinion on the state-of-the-art in transsphenoidal surgery for pituitary adenomas. The advantages and limitations of each approach are assessed and compared from a technical standpoint, and their reported outcomes evaluated in the framework of this transition phase. Available evidence should be interpreted in light of individual patient characteristics and within the context of each medical center, taking into consideration the known impact that surgical expertise and multidisciplinary management hold on clinical outcomes.

Comparison of the Mineral Profile of Two Types of Horse Diet, Silage and Commercial Concentrate, and Their Impacts on Hoof Tensile Strength.

The type of diet that a horse consumes is one of the most important factors determining the mineral profile and tensile strength of its hooves, so the quality and nutritional value of the supplied feed are fundamental to achieving satisfactory hoof quality. The objective of this study was to compare the differences in the mineral concentrations of sodium (Na), potassium (K), magnesium (Mg), zinc (Zn), and Iron (Fe) between two diets, namely silage and a commercial concentrate, using atomic absorption spectrometry and to determine which led to higher increases in the hoof tensile strength of horses consuming these diets. Thirty-two Spanish horses were randomly divided into two groups, where the diet of the horses in group 1 was silage oat hay, and that of the horses in group 2 was a commercial concentrate and oat hay. Both diets were provided for 12 months. The hoof tensile strength was then measured using an Instron universal testing machine. Mg and Fe levels were higher (p < 0.05) in the silage than in the commercial concentrate, and hoof Mg, Zn, K, and tensile strength were also influenced by the hormonal stage (p < 0.05). The type of diet directly affected the hoof Mg, Zn, K, Na, and tensile strength (p < 0.05), which Mg, K and Na were higher in horses fed with concentrate. It was found that for each unit of Zn (µg/g and Na (µg/g)), in the hoof, the tensile strength is affected by −0.10 N/mm2 and −0.003 N/mm2, respectively for each mineral.

Interventions for the treatment of xerostomia: A randomized controlled clinical trial.

BACKGROUND: Xerostomia or dry mouth sensation corresponds to a common clinical problem that can significantly impair the oral health related quality of life (OHRQoL). Currently, there is a large variety of local agents available for the treatment of xerostomia, but there is a lack robust evidence supporting the use of one treatment over another. We aimed to compare the effectiveness of a 1% malic acid salivary stimulant spray with a 1.33% betaine-based saliva substitute mouthwash in the improvement of xerostomia. MATERIAL AND METHODS: Fifty-one participants with drug induced or idiopathic xerostomia were randomly allocated into three groups, two intervention and one control group (placebo). OHRQoL and severity of xerostomia were assessed with the OHIP-14sp questionnaire and a visual analogue scale (VAS) respectively. Stimulated and non-stimulated salivary flow rates before and after treatments were also measured. RESULTS: All three groups reported a significantly improvement in the dry mouth sensation and non-stimulated salivary flow rates, but only the malic acid spray and the betaine-based mouthwash significantly improved the OHRQoL. There were no significant differences between both intervention groups. CONCLUSIONS: This study provides evidence that both tested agents are comparable in improving the dry mouth sensation and OHRQoL of patients with drug induced and idiopathic xerostomia. Key words:Xerostomia, dry mouth, malic acid, betaine, oral-health related quality of life.

Systemization of a pharmacy technician career ladder in a multi-hospital system.

Purpose: Hospital consolidation into larger, systemized health systems has enabled system-wide standardization of promotion processes, including pharmacy technician career ladders. However, whether system standardization affects the job satisfaction or outcomes of pharmacy technicians is unknown. The purpose of this project was to assess pharmacy technician perceptions and outcomes after systemization of a pharmacy technician career ladder. Methods: Pharmacy technician satisfaction scores and outcomes (promotion and turnover rates) were assessed in an eight-hospital health system before and after systemization of a pharmacy technician career ladder. Results: Two hundred and forty-nine pharmacy technicians were employed during the pre-intervention (n = 104) and post-intervention (n = 145) time periods. One hundred and twenty-three of 145 (84.83%) pharmacy technicians completed a job satisfaction survey after implementation of the system-wide technician career ladder. Overall satisfaction for the career ladder averaged 3.8 ± 0.61 or between neutral to positive satisfaction. There was no difference in total satisfaction regardless of teaching (3.8 ± 0.59) or community hospital (3.8 ± 0.63) location (p = 0.53) or stratifying by Pharmacy Technician status. A total of 50 pharmacy technicians were hired during the study period, either during the pre-implementation (n = 36) or post-implementation (n = 14) time periods. Time to the first promotion averaged 1.73 ± 1.00 years in the pre-implementation period and 1.36 ± 0.55 years in the post-implementation period (p = 0.20). Technician voluntary turnover was similar between the time periods. Conclusion: In conclusion, the standardization of a systems-level pharmacy technician promotion ladder from a single hospital to a systems-level was associated with positive job satisfaction and similar promotions and turnover rates as the historic, single hospital-based promotion ladder.

Preliminary Study on the Connection Between the Mineral Profile of Horse Hooves and Tensile Strength Based on Body Weight, Sex, Age, Sampling Location, and Riding Disciplines.

Hoof mineral profile is important as it could affect locomotion. Factors such as body weight, sex, age, and riding disciplines affect hoof mineral profile. In Mexico and globally, studies are needed on the characterization of mineral profile of hooves and tensile strength, as this could help to prevent overgrowth or microfractures. Therefore, in the present survey, 165 samples of equine hoof cuttings from different sex, ages, breeds, and riding disciplines from different regions of Mexico were analyzed for their mineral composition, and a universal testing machine was used to measure tensile strength. More than half of the samples were from males (63%) and aged 3 to 5 years (52%). Most samples were obtained from horses used for reproduction (36%) and working (29%) purposes. The most preponderant minerals were K (3,416 µg/g), Na (2,242 µg/g), and Ca (631 µg/g). Tensile strength ranged from 1.2 to 45 N. Females had higher (P < 0.05) amounts of Zn than males. Animals younger than 3 years old have lower (P < 0.05) levels of Na than those between 3 and 5 years old. Horses used for reproduction had lower (P < 0.05) Mg concentrations than animals used for running and working. Tensile strength was similar between demographic characteristics. Horses from Santa Gertrudis military ranch had higher (P < 0.05) levels of Ca, Se, and Na compared with horses from other sampling location. Copper was higher (P < 0.05) in horses from racecourse. Potassium was higher (P < 0.05) in horses from the Presidential General Staff. Overall, there was no evident connection between sex, ages, breeds, and riding disciplines from different regions of Mexico and the mineral composition of the hoof or its tensile strength. Further research should focus on the relation on specific feeding regimes, horse individual characteristic, hoof mineral contents, and tensile strength.

Criterios STOPP-START y la prescripción inapropiada del anciano / STOPP/START criteria and inappropriate prescription in the elderly

Introducción: El envejecimiento no solo promueve daños moleculares y celulares con deterioro progresivo de las funciones del cuerpo, sino que este proceso trasciende a los tratamientos y predispone a las prescripciones potencialmente inapropiadas y a la polifarmacia. Esta situación complejiza la atención del anciano con mayor utilización de servicios sanitarios y gastos en medicamentos. Objetivo: Identificar posibles prescripciones potencialmente inapropiadas y estimar la influencia de factores biomédicos en la polifarmacia de los ancianos hospitalizados. Material y Métodos: Investigación cuasi-experimental estudio antes-después, que acopió información de variables biomédicas de las historias clínicas de 200 pacientes hospitalizados en el Centro de Investigaciones sobre Longevidad, Envejecimiento y Salud, se utilizaron los criterios STOPP-START para identificar prescripciones potencialmente inapropiadas; se realizaron pruebas para estadística descriptiva e inferencial (α=0,05). Resultados: Se identificaron al ingreso 349 prescripciones inapropiadas STOPP y 357 prescripciones inapropiadas START, la sección correspondiente al sistema nervioso central aportó el 24,8 por ciento de las prescripciones inapropiadas STOPP y el sistema cardiovascular reveló el 59,9 por ciento de las prescripciones inapropiadas START. La polifarmacia estuvo presente en el 43,0 por ciento de los ancianos y la comorbilidad fue la variable que mostró mayor fuerza de asociación con la polifarmacia (OR =8,65; IC-95 por ciento: 4,51-16,59), seguido por la presencia de dos o más prescripciones inapropiadas según los criterios STOPP. Conclusiones: Los criterios STOPP-START identifican prescripciones inapropiadas en el contexto sanitario cubano, todo lo cual impacta de forma negativa en la polifarmacia de los ancianos. El sistema nervioso central y el sistema cardiovascular mostraron el mayor número de prescripciones potencialmente inapropiadas(AU)

Introduction: Aging not only promotes molecular and cellular damage with progressive deterioration of body functions, but this process transcends treatments and predisposes to potentially inappropriate prescriptions and polypharmacy. This situation complicates the care of the elderly with greater use of health services and drug expenses. Objective: To identify possible potentially inappropriate prescriptions and estimate the influence of biomedical factors on polypharmacy in hospitalized elderly people. Material and Methods: Quasi-experimental before-after study which collected information on biomedical variables from the medical records of 200 hospitalized patients at the Longevity, Aging and Health Research Center. The STOPP/START criteria were used to identify potentially inappropriate prescriptions. Descriptive and inferential statistical tests were performed (α = 0.05). Results: A total of 349 inappropriate STOPP prescriptions and 357 inappropriate START prescriptions were identified upon admission. The section corresponding to the central nervous system contributed 24.8 percent of the inappropriate STOPP prescriptions and the cardiovascular system revealed 59.9 percent of the inappropriate START prescriptions. Polypharmacy was present in 43.0 percent of the elderly and comorbidity was the variable that showed the greatest strength of association with polypharmacy (OR = 8.65; 95 percent CI: 4.51-16.59), followed by the presence of two or more inappropriate prescriptions according to the STOPP criteria. Conclusions: The STOPP/START criteria identify inappropriate prescriptions in the Cuban healthcare context which has a negative impact on polypharmacy in the elderly. The central nervous system and the cardiovascular system showed the highest number of potentially inappropriate prescriptions(AU)

[Reversed halo sign as an unusual manifestation of cryptogenic organized pneumonia. Report of one case]. / Signo del halo invertido como manifestación inhabitual de neumonía organizada criptogénica. Reporte de un caso.

We report a 64 years old female admitted with fever, cough, dyspnea and lung opacities in the chest X ray. A chest tomography scan (CTS) showed multiple-bilateral ring-shaped opacities and the reversed halo sign (RHS). The patient did not improve with antimicrobial therapy (AT). Infection and rheumatologic causes were excluded, therefore Cryptogenic organizing pneumonia (COP) was suspected with compatible percutaneous biopsy. Systemic steroids were started with a good clinical response. The patient was discharged four weeks after admission in good general conditions and practically no lungs opacities.

Signo del halo invertido como manifestación inhabitual de neumonía organizada criptogénica: reporte de un caso / Reversed halo sign as an unusual manifestation of cryptogenic organized pneumonia: report of one case

We report a 64 years old female admitted with fever, cough, dyspnea and lung opacities in the chest X ray. A chest tomography scan (CTS) showed multiple-bilateral ring-shaped opacities and the reversed halo sign (RHS). The patient did not improve with antimicrobial therapy (AT). Infection and rheumatologic causes were excluded, therefore Cryptogenic organizing pneumonia (COP) was suspected with compatible percutaneous biopsy. Systemic steroids were started with a good clinical response. The patient was discharged four weeks after admission in good general conditions and practically no lungs opacities.

Impact of 1% malic acid spray on the oral health-related quality of life of patients with xerostomia.

Dry mouth sensation, also known as xerostomia, is a common clinical problem with an increasing prevalence. Although recent studies have reported promissory results of malic acid, none have evaluated the impact of malic acid on the oral health-related quality of life (OHRQoL) of patients with xerostomia. Thus, this study aimed to evaluate the impact of 1% malic acid, combined with fluoride and xylitol, on the OHRQoL of patients with xerostomia. We enrolled 70 patients and randomly allocated them into two groups: the intervention group (applied topical sialogogue with 1% malic acid) and the control group (applied a placebo). We assessed the OHRQoL and severity of xerostomia before and after treatment with the Spanish version of the Oral Health Impact Profile-14 questionnaire (OHIP-14sp) and a visual analogue scale (VAS), respectively. In addition, stimulated and non-stimulated salivary flow rates before and after treatments were also measured. In total, 60 patients completed the study. According to the VAS, both sprays significantly improved dry mouth sensation (P < 0.001). However, OHIP-14sp total scores decreased significantly in the intervention group from 20.8 ± 10.4 to 16.5 ± 9.5 (P < 0.001), indicating an improvement in the OHRQoL. No significant differences were observed in the control group (P > 0.05). Furthermore, non-stimulated salivary flow rates significantly increased in the intervention group from 0.25 ± 0.22 to 0.33 ± 0.33 mL/min (P < 0.001). Overall, this study demonstrated that malic acid improves the OHRQoL and dry mouth sensation in patients with xerostomia.

Alveolar soft-part sarcoma of the masseter and mandibular ramus: Report of a case and review of the literature.

Alveolar soft-part sarcomas are clinically and morphologically distinct soft-tissue sarcomas, with an unknown histogenesis. When the tumors affect the region of the head and neck, they are often located in the orbit and tongue. We report a case of an alveolar soft-part sarcoma in the left masseter of a 28-year-old female. The patient had chronic pain and paresthesia of her left lower lip. Panoramic radiography and computed tomography showed a well-delimited radiolucent mass in the left ramus. An incisional biopsy was performed, and the sample submitted for histopathological study. The tumor showed positive periodic acid-Schiff diastase-resistant granules. Immunohistochemically, the tumor cells were diffusely positive for myoglobin, and focally positive for actin and desmin.

Analysis of the complete organellar genomes of the rockweed Fucus spiralis (Fucaceae, Phaeophyceae) supports its infraspecific recognition as Fucus vesiculosus var. spiralis.

Fucus spiralis L. is a broadly distributed monoecious intertidal seaweed. The specific status of F. spiralis however is debatable. Here, we contribute to the bioinformatics and systematics of F. spiralis by analysing the complete mitochondrial and plastid genomes of a specimen from California, U.S.A. The F. spiralis mitogenome is 36,396 base pairs (bp) in length and contains 67 genes, and the plastid genome is 125,066 bp in length and contains 171 genes. The F. spiralis genomes are 99.7% and 99.8% similar in nucleotide sequence to F. vesiculosus, and support the revised classification of F. spiralis to Fucus vesiculosus var. spiralis.

Utilidad de tinción de tricrómico de Masson en la cuantificación de densidad media vascular en mucosa oral normal, displasia epitelial y carcinoma oral de células escamosas / Utility of Masson's trichrome stain in the quantification of mean vascular density in normal oral mucosa, epithelial dysplasia and oral squamous cell carcinoma

RESUMEN: El objetivo de este estudio fue valuar la utilidad del uso de la tinción de Tricrómico de Masson (TM) en la cuantificación de la densidad media vascular (DMV) en Mucosa Oral Normal (MON), Displasia Epitelial Oral (DEO) y Carcinoma Oral de Células Escamosas (COCE). Estudio descriptivo de serie de casos. Se analizaron 17 muestras de MON, 15 muestras de DEO y 16 de COCE, teñidas con TM. Para determinar su utilidad, se compararon con las mismas muestras analizadas con técnica de inmunohistoquímica contra CD31. La cuantificación de la DMV se realizó en las 3 áreas de mayor vascularización de cada muestra. Se determinó la DMV según diagnóstico mediante la tinción TM e inmunohistoquímica contra CD31, y se calculó la correlación entre ambos. La DMV cuantificada con TM y contra CD31 difiere según el diagnóstico, observándose un aumento de la DMV al malignizarse el diagnóstico. No se encontraron diferencias al comparar la DMV cuantificada con TM y contra CD31. La correlación de la DMV analizado por TM y contra CD31 es significativa y moderada. La cuantificación de vasos sanguíneos es posible mediante la tinción de TM en muestras de MON, DEO y COCE, con una correlación moderada con la inmunohistoquímica contra CD31.

SUMMARY. The objective of this study was to evaluate the utility of Masson's Trichrome (TM) staining in the quantification of the mean vascular density (DMV) in samples of normal oral mucosa (MON), oral epithelial dysplasia (ODE) and oral squamous cell carcinoma (COCE). The design - a descriptive study of case series. We analyzed 17 samples of MON, 15 samples of DEO and 16 samples of COCE, stained with TM. To determine usefulness, we compared and analyzed the same samples, either stained with TM or with immunohistochemical technique against CD31. Quantification of the DMV was performed in the 3 areas of greatest vascularization in each sample. DMV was determined according to diagnosis by TM staining and immunohistochemistry against CD31, and the correlation between the two was then calculated. DMV quantified with TM and against CD31 differs according to the diagnosis, with an increase in DMV upon malignant diagnosis. No differences were found when comparing DMV quantified with TM and against CD31. The correlation of the DMV analyzed by TM and against CD31 is significant and moderate. Quantification of blood vessels is possible by TM staining in samples of MON, DEO and COCE. TM staining is moderately correlated with immunohistochemistry against CD31.

Inmunoexpresión de E-cadherina y vimentina en mucosa oral normal, displasia epitelial oral y carcinoma oral de células escamosas / Immunoexpression of E-cadherin and vimentin in normal oral mucosa, oral epithelial displasia and oral squamous cell carcinoma

El objetivo fue evaluar la inmunoexpresión de E-cadherina y Vimentina en mucosa oral normal (MON), displasia epitelial oral (DEO) y carcinoma oral de células escamosas (COCE). Se realizó un estudio descriptivo de una serie de casos analizandolos mediante técnica de inmunohistoquímica contra E-cadherina y Vimentina 16 muestras de MON, 16 de DEO y 19 de COCE. La inmunotinción fue evaluada cualitativamente considerando extensión e intensidad para E-cadherina e intensidad para Vimentina. El análisis de la extensión e intensidad de la inmunotinción de E-cadherina y Vimentina según diagnóstico reveló una asociación estadísticamente significativa (p<0,001). Siendo la expresión de E-cadherina más alta en MON, seguido por DEO y más baja en COCE, inversamente a lo que se observó con Vimentina. El presente estudio reveló la subregulación del marcador molecular E-cadherina junto con la expresión aberrante por parte de células epiteliales del marcador mesenquimal Vimentina en muestras de MON, DEO y COCE.

The aim was to evaluate the expression of E-cadherin and Vimentin in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC), in comparison with normal oral mucosa (NOM) in a descriptive case study using immunohistochemistry. A total of fifty-one (N=51) histological samples were included; as follows: n = 16 (NOM), n = 16 (OED) and n = 19 (OSCC). All samples were analyzed using immunohistochemistry against the expression of E-cadherin and Vimentin. Immunostaining was qualitatively evaluated by extent and intensity of its expression for E-cadherin and intensity for Vimentin. Extension and intensity analysis of E-cadherin and Vimentin immunostaining according to group revealed a statistically significant association (r<0.001). E-cadherin expression was found to be highest in NOM followed by OED and lowest in OSCC, inverse to what was observed with Vimentin. The present study revealed the down regulation of the molecular marker E-cadherin, suggestive of reduction in dysplastic cells on comparison to NOM cells, and aberrant expression of the mesenchymal marker Vimentin by epithelial cells in samples of NOM, OED and OSCC; questioning their value as a prognostic marker.

Antimicrobial Properties of Copper Nanoparticles and Amino Acid Chelated Copper Nanoparticles Produced by Using a Soya Extract.

This paper reports a comparison of the antibacterial properties of copper-amino acids chelates and copper nanoparticles against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. These copper-amino acids chelates were synthesized by using a soybean aqueous extract and copper nanoparticles were produced using as a starting material the copper-amino acids chelates species. The antibacterial activity of the samples was evaluated by using the standard microdilution method (CLSI M100-S25 January 2015). In the antibacterial activity assays copper ions and copper-EDTA chelates were included as references, so that copper-amino acids chelates can be particularly suitable for acting as an antibacterial agent, so they are excellent candidates for specific applications. Additionally, to confirm the antimicrobial mechanism on bacterial cells, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was carried out. A significant enhanced antimicrobial activity and a specific strain were found for copper chelates over E. faecalis. Its results would eventually lead to better utilization of copper-amino acids chelate for specific application where copper nanoparticles can be not used.

Morphea "en coup de sabre": An unusual oral presentation.

Morphea, or localized scleroderma, is an inflammatory disease that leads to sclerosis of the skin and underlying tissues due to excessive collagen deposition. Oral involvement is unusual and it may produce white linear fibrotic areas with a scar-like appearance, atrophy of tongue papillae, gingival recession and alveolar bone resorption. We report a case of a 13-year-old girl who consulted for progressive recession on the attached gingiva of her upper left incisors. She also presented a hypopigmented line on the left side skin of her upper lip, which continued through the vermilion and the lip mucosa, including the gingiva of the affected teeth. Clinical examination, blood tests, computerized axial tomography, echo-Doppler ultrasound and histopathological evaluation confirmed the diagnosis of morphea. Treatment with methotrexate and systemic corticosteroids was conducted. After 24 months, no other lesions appeared. No adverse side effects have been reported so far. Key words:Localized scleroderma, oral morphea, linear scleroderma, oral involvement, intraoral lesions.

Difference in EGFR expression and mean vascular density in normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma

To evaluate the expression of the epidermal growth factor receptor (EGFR) and mean vascular density (MVD) in normal oral mucosa (NOM), oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Material and methods: Descriptive case study. Nineteen histological samples diagnosed with NOM, 18 diagnosed with OED, and 19 with OSCC, were analyzed with immunohistochemistry against EGFR and CD31. EGFR expression was evaluated by extent and intensity of its expression in normal, dysplastic and neoplastic epithelium. MVD was determined through the detection of blood vessels by antibodies against CD31. Results: Extension of EGFR expression was highest in OSCC followed by OED and lowest in NOM, resulting in significant different between the degrees of extension (p<0.001). Intensity of EGFR was similar in NOM, OED and OSCC, without differences in its expression (p=0.533). Differences in MVD were found between NOM and OSCC groups (p<0.01), and between OED and OSCC groups (p<0.01), with no differences between NOM and OED groups (p=0.91). MVD was 21.17 +/- 4.98 in NOM, 23.40 +/- 5.77 in OED and 33.92 +/- 8.39 in OSCC. Conclusion: EGFR is expressed in normal, dysplastic or neoplastic oral epithelium. However, the extent of its expression is greater as malignancy increases. MVD varies according to the diagnosis.