Anti-inflammatory and/or immunomodulatory activities of Uncaria tomentosa (cat's claw) extracts: A systematic review and meta-analysis of in vivo studies.

Background: Uncaria tomentosa (Willd. ex Schult.) DC. (Rubiaceae) is traditionally used by Amazonian indigenous groups to treat inflammatory diseases. To date, there are no systematic reviews and meta-analyses on the use of U. tomentosa for inflammation control in animals supporting the traditional knowledge about this species. This study was conducted to evaluate the effect of U. tomentosa extracts in modulating inflammatory mediators and to determine which types of inflammatory diseases can be treated by this species. Methods: We conducted a systematic review and meta-analysis of preclinical studies published before 26 July 2023, identified in PubMed, Embase, and Scopus. Four independent reviewers extracted the data and assessed the risks of bias. The effects of U. tomentosa on inflammatory diseases and the inflammatory mediators involved were extracted from the studies. Standardized mean differences (SMD) and 95% confidence intervals (95%CI) of the outcomes were estimated. The meta-analyses were conducted using RevMan 5.4 (Cochrane Collaboration). This protocol was registered in PROSPERO (CRD42023450869). Results: Twenty-four of 523 studies were included. U. tomentosa extracts decreased the cytokines interleukin (IL)-6 (SMD: -0.72, 95%CI: -1.15, -0.29, p = 0.001) and transcription factor nuclear factor kappa-B (NF-κB) (SMD: -1.19, 95%CI: -1.89, -0.48, p = 0.001). However, the extracts did not significantly alter IL-1 (SMD: -0.16, 95%CI: -0.87, +0.56, p = 0.67), IL-10 (SMD: -0.05, 95%CI:-0.35, 0.45, p = 0.80), or tumor necrosis factor-alpha (TNF-α) levels (SMD: 0.18, 95%CI: -0.25, 0.62, p = 0.41). Conclusion: Many extracts of stem bark, roots, and leaves of U. tomentosa, mostly aqueous and hydroethanolic, exhibited anti-inflammatory and/or immunomodulatory activities and low toxicity. The extracts decreased NF-κB and IL-6. These findings suggest that this species has the potential to treat inflammatory diseases in which these markers are increased, according to the ethnopharmacological use. These activities are not related to a specific class of compounds.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450869, Identifier CRD42023450869.

Do on- and off-pump coronary bypass surgery differently affect perioperative peripheral tissue metabolism?

BACKGROUND: Microdialysis allows the in-vivo assessment of interstitial fluids. We studied the metabolic status of peripheral tissues (skeletal muscle) in patients undergoing coronary artery bypass surgery on- (CABG) or off-pump (OPCAB). METHODS: Twenty patients candidates to elective coronary bypass surgery were randomly assigned to undergo CABG or OPCAB. A microdialysis catheter was inserted in the left deltoid muscle before surgery and left in place for 24 hours, and metabolic markers of peripheral tissue perfusion (glucose, lactate, pyruvate, glycerol and lactate/pyruvate (L/P) ratio) were assessed before, at the end, and 24 hours after surgery. RESULTS: Preoperative clinical features were similar in both groups. Interstitial levels of glucose and lactate increased over time, being in both groups significantly higher than baseline 24 hours after surgery, whereas glycerol levels did not change over time and between groups. In addition, there was an increase over time of pyruvate levels which were significantly higher in CABG after surgery, whereas L/P ratio was significantly higher in OPCAB 24 hours after surgery. CONCLUSION: Metabolic changes after coronary bypass surgery occur with some differences related to CPB use. Overall, these changes suggest that, after coronary surgery, a certain degree of hypermetabolic state ensues, lasting up to 24 hours after surgery; the postoperative increase in pyruvate levels in CABG patients, together with the changes in L/P ratio occurring only in OPCAB patients implies an higher risk of tissue hypoperfusion/ischemia for patients submitted to OPCAB, although this does not lead to permanent cellular damage, as the markers of this complication (e.g., glycerol) do not change over time.

Review: nanocomposites in food packaging.

The development of nanocomposites is a new strategy to improve physical properties of polymers, including mechanical strength, thermal stability, and gas barrier properties. The most promising nanoscale size fillers are montmorillonite and kaolinite clays. Graphite nanoplates are currently under study. In food packaging, a major emphasis is on the development of high barrier properties against the migration of oxygen, carbon dioxide, flavor compounds, and water vapor. Decreasing water vapor permeability is a critical issue in the development of biopolymers as sustainable packaging materials. The nanoscale plate morphology of clays and other fillers promotes the development of gas barrier properties. Several examples are cited. Challenges remain in increasing the compatibility between clays and polymers and reaching complete dispersion of nanoplates. Nanocomposites may advance the utilization of biopolymers in food packaging.

Fenoldopam to prevent renal replacement therapy after cardiac surgery. Design of the FENO-HSR study.

INTRODUCTION: Acute kidney injury requiring renal replacement therapy is a serious complication following cardiac surgery associated with poor clinical outcomes. Until now no drug showed nephroprotective effects. Fenoldopam is a dopamine-1 receptor agonist which seems to be effective in improving postoperative renal function. The aim of this paper is to describe the design of the FENO-HSR study, planned to assess the effect of a continuous infusion of fenoldopam in reducing the need for renal replacement therapy in patients with acute kidney injury after cardiac surgery. METHODS: We're performing a double blind, placebo-controlled multicentre randomized trial in over 20 Italian hospitals. Patients who develop acute renal failure defined as R of RIFLE score following cardiac surgery are randomized to receive a 96-hours continuous infusion of either fenoldopam (0.025-0.3 µg/kg/min) or placebo. RESULTS: The primary endpoint will be the rate of renal replacement therapy. Secondary endpoints will be: mortality, time on mechanical ventilation, length of intensive care unit and hospital stay, peak serum creatinine and the rate of acute renal failure (following the RIFLE score). CONCLUSIONS: This trial is planned to assess if fenoldopam could improve relevant outcomes in patients undergoing cardiac surgery who develop acute renal dysfunction. Results of this double-blind randomized trial could provide important insights to improve the management strategy of patients at high risk for postoperative acute kidney injury.

Cytological and histological diagnosis of lung cancer in Sardinia and Italy in the 1990s.

BACKGROUND: Up to 30-50% of all lung cancer cases remain without cyto-histological characterisation. The aim of our study was to evaluate retrospectively the proportion of histological and/or cytological diagnosis in patients with lung cancer in Sardinia. METHODS: Data was gathered by consulting the hospital registers and case notes of individual patients released from hospital with a diagnosis of Lung Cancer at all medical centres throughout Sardinia. In gathering patients' data, we focused our attention on cytological and histological procedures through which allowed the lung cancer was diagnosed. Cancer Registries data was utilised to compare our data with national and Sassari province data. RESULTS: From 1991 to 1996 there was a total of 3146 lung cancer patients registered in Sardinia. 1902 patients (60.5%) had a histological diagnosis, 142 patients (4.5%) a cytological diagnosis while in 1102 patients (35%) the diagnosis was performed without any pathological validation. CONCLUSIONS: Our study has shown that lung cancer diagnosis is supported by pathological verification in 65% of cases while in remaining 35% of patients the diagnosis is based only on clinical and radiological reports. In Italy data from Cancer Registries report the percentage of cytohistological diagnosis to be 70% with the percentage of cytological diagnosis being higher than in Sardinia.

Sudden death in epilepsy: an experimental animal model.

INTRODUCTION: The physiopathogenetic mechanisms possibly involved in sudden unexplained epileptic death (SUDEP), were investigated in the hemispherectomized rat. METHODS: For this purpose, paroxysmal activity, vagal nerve firing, systemic blood pressure (BP), pulmonary artery pressure, and ECG were simultaneously recorded in an experimental animal model of epilepsy. Recordings were performed in basal conditions and during paroxysmal activity induced by topical application of penicillin-G at hypothalamic and mesencephalic level. During the experiment were also performed hemogas analysis and at end, samples of lung tissue were processed for histology. RESULTS: Activation of hypothalamic (HEF) and mesencephalic (MEF) epileptic foci induced a significant increase of spontaneous vagal nerve firing that was strictly correlated to ECG impairments and hypotension. When paroxysmal activity extinguished, vagal nerve activity and cardiovascular parameters returned to basal conditions. However, in 25% of the animals, co-activation of HEF and MEF always triggered a vagal hypertone which was temporally correlated to cardiac arrhythmias, but also to hyperkalemia, acidosis, pulmonary hypertension and to animal death. Histological control in lungs of deceased animals showed an alveolar and perivessel oedema with an oedematous infiltration in the alveolar and bronchial spaces and mucous secretion. During ictal activity, comparison between survived and deceased animals showed significant differences in the incidence of ECG impairment of pulmonary artery pressures, pO2, and pCO2 pressures, and [K+], [HCO3-], and [pH], concentrations. DISCUSSION: A possible explanation of the above observations is discussed in relationship to SUDEP physiopathogenesis.

Epidemiology of lung cancer in Sardinia, Italy, from 1980 to 1996.

SETTING: Bronchial carcinoma is the most common cause of death among all malignant tumours. Despite a progressive increase, many Italian regions--ours included--do not have a Regional Cancer Registry. OBJECTIVE: To assess lung cancer incidence and mortality rates in Sardinia during the period 1980-1996. METHODS: Data were gathered by consulting hospital registers and the case notes of individual patients released from hospital with a diagnosis of bronchial carcinoma at all Sardinian medical centres between 1980 and 1996. RESULTS: A total of 7734 patients with lung cancer were registered in Sardinia between 1980 and 1996. Data showed a steady increase in lung cancer incidence rates over the years (from 22.3/100000 in 1980 to 34.5 in 1996). The same increase was evident in mortality rates (from 25.7/100000 in 1980 to 42.9 in 1996). The increase in mortality rates was higher in women (+146%) than in men (+59.5%). CONCLUSIONS: Results show a slow but steady increase in lung cancer incidence and mortality rates in Sardinia. The high number of smokers among lung cancer patients seems to indicate that anti-smoking campaigns need to be more effective in Sardinia.

Preparaciones de base líquida vs. citología convencional: Adecuación de las muestras y coincidencia de diagnóstico en lesiones orales / Liquid-based preparations versus conventional cytology: specimen adequacy and diagnostic agreement in oral lesions

Objetivo: Comparar la efectividad de la muestra y la coincidencia de diagnóstico entre preparaciones de base líquida y frotis convencionales en lesiones orales, y probar la viabilidad de la prueba inmuno-citoquímica en preparaciones de baselíquida de lesiones de carcinoma oral. Material y Métodos: Se obtuvieron muestras de 44 pacientes. Primeramente se prepararonfrotis convencionales, usando un dispositivo cytobrush.A continuación se sumergió el cepillo que contenía el material residual en un líquido conservante. La muestra en el mismo fue procesada de acuerdo con las indicaciones del fabricante(AutoCyte, Inc. Elon College, North Carolina, USA). Se tiñeron preparaciones de ambas técnicas de acuerdo con el método de Papanicolaou. Para la prueba inmuno-citoquímica se usaron conjuntamente AE1/AE3 (Dako, CA, USA) para las lesiones de carcinoma oral, de acuerdo con el método de la Estreptovidina-biotina-peroxidasa. Se usó la prueba exacta de Fisher; fijándose la probabilidad significativa en p ≤ 0.05. Resultados: Ambas técnicas coincidieron en el diagnóstico citológico en todos los casos donde se usó una muestra adecuada; en 3 casos el frotis convencional mostró hipocelularidad y, por lo tanto, resultó inadecuado para el análisis. En el análisis de muestras, la citología de base líquida mostró una mejora general estadísticamente significativa), de un 41% en espesura de frotis y de un 66% en la distribución de células (p ≤ 0.05), además de una reducción en la superposición de células y la presencia de sangre (p ≤ 0.05). La morfología celular se observó mejor en las preparaciones de base líquida. Las reacciones de la prueba inmuno-citoquímica fueron positivas en todos los casos de malignidad, siendo especialmente clara la observación de células inmuno-marcadas. Conclusión: Tanto las preparaciones de base líquida como los frotis convencionales son dignos de confianza desde el punto de vista del diagnóstico; el método de base líquida mostró una mejora general en la preservación de muestras, adecuación de ejemplares, observación de morfología celular y reproducibilidad

Objective: To compare specimen adequacy and diagnostic agreement between liquid-based preparations and conventional smears in oral lesions, and to test the viability of immunocy to chemical assay in liquid-based preparations from oral carcinoma lesions. Material and Methods: Samples were collected from 44 patients. Conventional smears were prepared first, using a cytobrush device. Then the brush, containing the residual material, was immersed in a preservative fluid. The sample in the preservative fluid was processed according to the manufacturer directions (AutoCyte, Inc. Elon College, North Carolina, USA). Slides of both techniques were stained by Papanicolaou method. For immunocytochemical assay, a cytokeratin pool AE1/AE3 (Dako, CA, USA) was applied in liquid-based preparations from oral carcinoma lesions following the Streptavidin-biotin-peroxidase method. Fisher’s exact test was used; significance was set for p ≤0.05.Results: Both techniques agreed on cytologic diagnosis in every case they yielded an adequate specimen; in 3 cases conventional smear resulted in hypocellularity and therefore inadequate for analysis. On specimen analysis, the liquid-based cytology demonstrated a statistically significant, 41% overall improvement in smear thickness and 66% in cell distribution (p ≤0.05), and a reduction in cell overlapping and presence of blood (p ≤0.05). The cell morphology was better visualized in the liquid-based preparations. The immunocytochemical assay reactions were positive in all malignant cases, the visualization of the immunostained cells being especially clear.Conclusion: Both, the liquid-based preparation and conventional smear, are diagnostically reliable; the liquid-based method showed an overall improvement on sample preservation, specimen adequacy, visualization of cell morphology and reproducibility

Liquid-based preparations versus conventional cytology: specimen adequacy and diagnostic agreement in oral lesions.

OBJECTIVE: To compare specimen adequacy and diagnostic agreement between liquid-based preparations and conventional smears in oral lesions, and to test the viability of immunocytochemical assay in liquid-based preparations from oral carcinoma lesions. MATERIAL AND METHODS: Samples were collected from 44 patients. Conventional smears were prepared first, using a cytobrush device. Then the brush, containing the residual material, was immersed in a preservative fluid. The sample in the preservative fluid was processed according to the manufacturer directions (AutoCyte, Inc. Elon College, North Carolina, USA). Slides of both techniques were stained by Papanicolaou method. For immunocytochemical assay, a cytokeratin pool AE1/AE3 (Dako, CA, USA) was applied in liquid-based preparations from oral carcinoma lesions following the Streptavidin-biotin-peroxidase method. Fisher's exact test was used; significance was set for P < or = 0.05. RESULTS: Both techniques agreed on cytologic diagnosis in every case they yielded an adequate specimen; in 3 cases conventional smear resulted in hypocellularity and therefore inadequate for analysis. On specimen analysis, the liquid-based cytology demonstrated a statistically significant, 41% overall improvement in smear thickness and 66% in cell distribution (P < or = 0.05), and a reduction in cell overlapping and presence of blood (P < or = 0.05). The cell morphology was better visualized in the liquid-based preparations. The immunocytochemical assay reactions were positive in all malignant cases, the visualization of the immunostained cells being especially clear. CONCLUSION: Both, the liquid-based preparation and conventional smear, are diagnostically reliable; the liquid-based method showed an overall improvement on sample preservation, specimen adequacy, visualization of cell morphology and reproducibility.

Original insight into continuous cardiac output monitoring: "TruCCOMS". Correlation with other methods.

AIM: Of all technical devices used for continuous or intermittent monitoring of cardiac output, in our clinical practice during the last year, we tested a new system, the true continuoas cardiac output monitoring system (TruCCOMS), for the continuous real time measurement of cardiac output. The purpose of this study was to compare the accuracy, reliability and promptness of TruCCOMS with other systems and methods of cardiac output (CO) measurement such as pulsion continuous cardiac output (PiCCO) and end diastolic Area (EDA) determination by trans-esophageal-echocar-diography (TEE), keeping as gold standard for CO measurement the thermodilution method by Swan-Ganz. METHODS: Sixteen male patients, aged 50 to 60 years, with ejection fraction (FE) >50%, EUROSCORE=1, who underwent CABG surgery with circulation extra corporeal (CEC), were analysed with all methods mentioned above. The measurements were obtained at different phases: pre-CEC; post-CEC; and Intensive Care Unit (ICU). In the ICU setting, 5 patients classified as under-filled with a pulmonary capillary wedge pressure (PCWP) =/<8 mmHg were filled until a PCWP gs;13 mmHg in order to evaluate the promptness of the various systems to detect the new condition. RESULTS: The statistical analysis of data obtained in our survey, clearly demonstrates that TruCCOMS is at least equivalent to average thermo-dilution cardiac output (AvTDCO), with the advantage of being continuous, real time and, furthermore, with no need for physician intervention/interference. CONCLUSION: In our experience the TruCCOMS seems to be an ideal method for continuous cardiac output (CCO) monitoring compared with the other bedside systems challenged.

Effects of lamination and coating with drying oils on tensile and barrier properties of zein films.

Zein films plasticized with oleic acid have been considered potentially useful for biodegradable packaging applications. However, moisture was found to affect their tensile and gas barrier properties. We investigated the effects of two converting processes, fusion lamination and coating with drying oils, on tensile properties and gas permeability of zein films. Zein films were laminated to 4-ply sheets in a Carver press and coated with tung oil, linseed oil, or a mixture of tung and soybean oils. Tensile properties and permeability to water vapor, oxygen, and carbon dioxide were measured according to ASTM methods. Laminated films were clearer, tougher, and more flexible, and had a smoother finish than nontreated sheets. Lamination decreased O(2) and CO(2) permeability by filling in voids and pinholes in the film structure. Coating increased tensile strength and elongation and decreased water vapor permeability. Coatings acted as a composite layer preventing crack propagation and increasing film strength. They also formed a highly hydrophobic surface that prevented film wetting.

Three cases of cardiac hydatidosis: diagnosis, surgical treatment, and complications.

Three cases of cardiac hydatid disease from among the many cases of hydatidosis (>300) in various organs observed by the authors are reported. The sites of the cysts and the complications that arose are described. The first case developed hydatid pulmonary embolism caused by rupture into the right ventricular cavity, the second suffered peripheral hydatid embolism caused by rupture into the left ventricular cavity, and the third, whose diagnosis was fortuitous, had no complications. The first patient died shortly after admission. The other two underwent radical pericystectomy and partial pericystectomy with cardiopulmonary bypass. The best result was obtained in the third case where rupture had not occurred. The second patient recovered but developed hemiparesis. The various diagnostic tools available are discussed, as well as some technical aspects of pericystectomy, which has a high mortality rate. The importance of early diagnosis and treatment of this rare localization of Echinococcus granulosus is emphasized, and echocardiography is recommended even for nonspecific cardiac symptoms in areas where the parasite is endemic.

Tensile properties and water absorption of zein sheets plasticized with oleic and linoleic acids.

Corn zein has been investigated for fabrication of biodegradable packaging materials. Our objective was to investigate the effect of added plasticizers, oleic and linoleic acids, on tensile properties and water absorption of zein sheets. Moldable resins were precipitated from aqueous ethanol dispersions of zein and fatty acids and rolled into sheets of approximately 0.5 mm in thickness. To increase plasticization effects, zein-oleic acid sheets were replasticized by heating them in fatty acid baths. Plasticization resulted in flexible sheets of high clarity, low modulus, and high elongation and toughness, although low tensile strength. Water absorption of zein sheets was lowered by plasticization, attributed in part to reduced mass fraction of zein. Polymerization of linoleic acid may have sealed off pores on sheet surfaces, thus slowing water absorption.

[Aplasia and hypoplasia of the optic nerve. Comparison of 2 cases]. / Aplasia ed ipoplasia del nervo ottico. Comparazione di due casi.

Hypoplasia and aplasia of the optic nerve are congenital anomalies characterized respectively by a marked volume reduction (very small papilla, often identifiable only as a rosy-yellowish area from which the retinal vessels emerge) and by the absence of the optic disk (absence of the nerve and mainly of its vessels) and of the visual functions. These anomalies are often associated with malformations of the central nervous system and of the ocular structures. The defects originate in the embryonal period due to the arrested development of the mesodermal component towards the head of the optic nerve. The aim of this study is to try to interpret the different clinical manifestations of the disease by observing two cases (a female and a male) with a clinical picture of aplasia and hypoplasia of the optic nerve respectively. Both cases presented the following clinical characteristics: developmental defects of the optic nerve, severe microcephaly, positive IgG antibodies against CMV. The association of the optic nerve defect with microcephaly is due to the embryogenic origin of the optic vescicle by prosencephalon. The resulting clinical picture is probably the outcome of an interfering process that the authors have presumed in CMV intrauterine infection, after having excluded the most frequent teratogenic agents (maternal diabetes, tabagism, intake of alcohol ad drugs). Moreover, the different degree of ocular involvement and the different time of onset of the intrauterine pathogenic insult in the two cases could account for the different clinical pictures.

[Temperature monitoring and sites of measurement of body temperature]. / Monitoraggio termometrico e siti di rilevamento della temperatura corporea.

The authors report an investigation of 331 consecutive patients submitted to major surgery to evaluate the reliability of temperature monitoring in different body sites in relation to central temperature. After having considered the minimal temperature changes and the difficulties due to the different techniques used, it is concluded that the measurement at the middle 3rd of the oesophagus is the most reasonable measurements site.

[The propofol-fentanyl-pancuronium combination in aorto-coronary bypass. Experience and personal caseload]. / L'associazione propofol-fentanyl-pancuronio nei by-pass aorto-coronarici. Esperienza e casistica personali.

The authors report the use of a total intravenous anaesthesia in CABG. An association of propofol-fentanyl-pancuronium with a bolus at induction, then with continuous perfusion was used. Hemodynamic and oxymetric data obtained from the right heart and radial artery samples show good hemodynamic stability during surgery. It is underlined that, in order to reduce possible hemodynamic changes it is very important to use, during the surgical procedure, the lowest drug concentration.

[Circulation effects of noradrenaline in hyperdynamic septic shock]. / Effetti circolatori della noradrenalina nello shock settico iperdinamico.

The authors report on a group of 8 patients in septic shock, treated with NA in association with dopamine and/or dobutamine, according to a personal therapeutic protocol. The use of NA in septic shock with low SVR showed an improvement in hemodynamic condition and a higher survival rate in the treated patients. During the study many clinical, laboratory and microbiologic data were also recorded.

[Reducing bleeding during extracorporeal circulation interventions by high doses of aprotinin]. / Riduzione del sanguinamento negli interventi in circolazione extracorporea mediante l'uso di alte dosi di aprotinina.

The great risk of severe infectious diseases transmission through blood transfusion, has increased during the last years the effort to reduce the bank blood and its derivates use. Many techniques have proposed to achieve this purpose during and post cardiopulmonary bypass: normovolemic hemodilution, perioperative blood autotransfusion, postoperative return of extra corporeal circuit and chest drains blood and the particular use of some drugs. In the last few years several reports have been presented in the literature concerning the reduction of intra and postoperative bleeding in cardiac surgery by high dose Aprotinin administration. A randomized study with the use of this pharmacologic agent is presented: a group of patients was treated with Aprotinin (shared in two subgroups receiving respectively a different dose of the drug) and a control group. The results were highly encouraging both because of the reduction of peri and postoperative bleeding and because of the bank blood use important reduction.

[Botallo's duct with pulmonary hypertension in the adult]. / Il dotto di Botallo con ipertensione polmonare nell'adulto.

A patent ductus arteriosus in adults is a rare eventuality. After correct diagnosis, an accurate evaluation of pulmonary vascular resistances is necessary with, in case of normality, a straightforward indication to surgery, because the evolution of the disease cannot be predicted. In case of pulmonary hypertension irreversible pulmonary vascular damage must be excluded. Haemodynamic data such as pressures, flows and resistance ratios are not reliable. According to the majority of Authors the value of pulmonary resistances seems to be more accurate, and when more then 8 u/m2 an histological specimen must be obtained. In our experience a comparative study between the Health and Edwards method and the Yamaki et al., one shows, confirmed by postoperative follow-up, a greater reliability of the second one.

[Peroperative blood autotransfusion in heart surgery]. / L'autoemotrasfusione peroperatoria in chirurgia cardiaca.

A drastic reduction in homologous blood or plasma transfusion becomes necessary to prevent the risks of severe infections disease transmission. The authors studied the possibility of homologous blood save in cardiac surgery by peroperative autotransfusion. This procedure, although it diminished the average blood bank requirements, above all for an unexplained decrease in postoperative bleeding, did not obtain the good results that other authors had with the technique of 2 or 3 preoperative withdrawal, storage and postoperative reinfusion. In future our trend is to associate preoperative and intraoperative withdrawals to take advantage of both techniques.