Diagnostic Salivary Tests for SARS-CoV-2.

The diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection relies on the detection of viral RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR) performed with respiratory specimens, especially nasopharyngeal swabs. However, this procedure requires specialized medical personnel, centralized laboratory facilities, and time to provide results (from several hours up to 1 d). In addition, there is a non-negligible risk of viral transmission for the operator who performs the procedure. For these reasons, several studies have suggested the use of other body fluids, including saliva, for the detection of SARS-CoV-2. The use of saliva as a diagnostic specimen has numerous advantages: it is easily self-collected by the patient with almost no discomfort, it does not require specialized health care personnel for its management, and it reduces the risks for the operator. In the past few months, several scientific papers, media, and companies have announced the development of new salivary tests to detect SARS-CoV-2 infection. Posterior oropharyngeal saliva should be distinguished from oral saliva, since the former is a part of respiratory secretions, while the latter is produced by the salivary glands, which are outside the respiratory tract. Saliva can be analyzed through standard (rRT-PCR) or rapid molecular biology tests (direct rRT-PCR without extraction), although, in a hospital setting, these procedures may be performed only in addition to nasopharyngeal swabs to minimize the incidence of false-negative results. Conversely, the promising role of saliva in the diagnosis of SARS-CoV-2 infection is highlighted by the emergence of point-of-care technologies and, most important, point-of-need devices. Indeed, these devices can be directly used in workplaces, airports, schools, cinemas, and shopping centers. An example is the recently described Rapid Salivary Test, an antigen test based on the lateral flow assay, which detects the presence of the virus by identifying the spike protein in the saliva within a few minutes.

Skin and cutaneous melanocytic lesion simulation in biomedical optics with multilayered phantoms.

The complex inner layered structure of skin influences the photon diffusion inside the cutaneous tissues and determines the reflectance spectra formation. Phantoms are very useful tools to understand the biophysical meaning of parameters involved in light propagation through the skin. To simulate the skin reflectance spectrum, we realized a multilayered skin-like phantom and a multilayered skin phantom with a melanoma-like phantom embedded inside. Materials used were Al(2)O(3) particles, melanin of sepia officinalis and a calibrator for haematology systems dispersed in transparent silicon. Components were optically characterized with indirect techniques. Reflectance phantom spectra were compared with average values of in vivo spectra acquired on a sample of 573 voluntary subjects and 132 pigmented lesions. The phantoms' reflectance spectra agreed with those measured in vivo, mimicking the optical behaviour of the human skin. Further, the phantoms were optically stable and easily manageable, and represented a valid resource in spectra formation comprehension, in diagnostic laser applications and simulation model implementation, such as the Monte Carlo code for non-homogeneous media.

Multispectral imaging and artificial neural network: mimicking the management decision of the clinician facing pigmented skin lesions.

Various instruments based on acquisition and elaboration of images of pigmented skin lesions have been developed in an attempt to in vivo establish whether a lesion is a melanoma or not. Although encouraging, the response of these instruments, e.g. epiluminescence microscopy, reflectance spectrophotometry and fluorescence imaging, cannot currently replace the well-established diagnostic procedures. However, in place of the approach to instrumentally assess the diagnosis of the lesion, recent studies suggest that instruments should rather reproduce the assessment by an expert clinician of whether a lesion has to be excised or not. The aim of this study was to evaluate the performance of a spectrophotometric system to mimic such a decision. The study involved 1794 consecutively recruited patients with 1966 doubtful cutaneous pigmented lesions excised for histopathological diagnosis and 348 patients with 1940 non-excised lesions because clinically reassuring. Images of all these lesions were acquired in vivo with a multispectral imaging system. The data set was randomly divided into a train (802 reassuring and 1003 excision-needing lesions, including 139 melanomas), a verify (464 reassuring and 439 excision-needing lesions, including 72 melanomas) and a test set (674 reassuring and 524 excision-needing lesions, including 76 melanomas). An artificial neural network (ANN(1)) was set up to perform the classification of the lesions as excision-needing or reassuring, according to the expert clinicians' decision on how to manage each examined lesion. In the independent test set, the system was able to emulate the clinicians with a sensitivity of 88% and a specificity of 80%. Of the 462 correctly classified as excision-needing lesions, 72 (95%) were melanomas. No major variations in receiver operating characteristic curves were found between the test and the train/verify sets. On the same data set, a further artificial neural network (ANN(2)) was then architected to perform classification of the lesions as melanoma or non-melanoma, according to the histological diagnosis. Having set the sensitivity in recognizing melanoma to 95%, ANN(1) resulted to be significantly better in the classification of reassuring lesions than ANN(2). This study suggests that multispectral image analysis and artificial neural networks could be used to support primary care physicians or general practitioners in identifying pigmented skin lesions that require further investigations.

Optical devices used for image analysis of pigmented skin lesions: a proposal for quality assurance protocol using tissue-like phantoms.

Different technological tools have been developed to aid in the diagnosis of pigmented skin lesions, including cameras working with conventional RGB colour systems, epiluminescence microscopy and spectrophotometric methods using visible and near infrared wavelengths. All the different procedures should provide in an objective and reproducible fashion quantitative measurements of the colour and shape features of a given skin mole. At present, many devices have been introduced in experimental stages for clinical diagnosis, mainly used to provide to the clinicians an objective, computer-assisted second opinion. As for any diagnostic instruments, optical devices should also be subjected to a dedicated quality assurance protocol in order to evaluate the response repeatability of each device (intra-instrument agreement) and to check the accordance among the responses of different devices (inter-instrument agreement). The aim of this study was to design a quality assurance protocol for optical devices dedicated to image analysis of pigmented skin lesions and, in case, to detect cutaneous melanoma by using suitable tissue-like phantoms as standard references that enable testing of both hardware and software components. As an example, we report the results of intra-instrument and inter-instrument agreement when the protocol was applied on a series of 30 SpectroShade instruments, a novel optical device based on multi-spectral image analysis of colour and shape features of pigmented skin lesion.

A paradoxical acute effect of levodopa in de novo parkinsonian patients: worsening of some bradykinetic components.

Reports of alterations of reaction times (RTs) in Parkinson's disease are often discordant, particularly when the aim of the research is investigation of the relationship between levodopa (LD) administration and RTs. Slowing of simple RT in a group of de novo parkinsonian patients 30-90 min after administration of LD (Madopar 250) was recently reported. This temporary phenomenon was attributed to a sedative effect of LD. Our present study aimed to repeat these investigations using Multiple Delayed Reaction Verbochronometry (MDRV). We conclude that such a slowing is not a temporary phenomenon but may represent the increased time necessary for the subject to adequately perform the reaction tasks.

Optical imaging and automated melanoma detection: questions and answers.

Early detection and prompt excision of cutaneous melanoma is of paramount importance to improve patient survival, and the clinician should be aware of the clinical features that suggest the presence of a malignant lesion. The clinical diagnosis is mainly based on observation of the colour and shape of a given skin lesion. Unfortunately, evaluation of a pigmented lesion is to a large extent subjective and is closely related to the experience of the clinician. To overcome this problem, optical imaging techniques using different instrumentation (i.e. colour video camera, epiluminescence microscopy, reflectance spectrophotometry) and computer image analysis have been proposed in an attempt to provide quantitative measurements in an objective and reproducible fashion. The different procedures employed to perform the diagnosis automatically all have a common denominator: mimicking the eye and the brain of the clinician by image processing and computerized analysis programs, respectively. Sensitivity and specificity data reported in the literature suggest that the computer-based diagnosis of melanoma does not greatly differ from the diagnostic capability of an expert clinician, and is independent of the optical acquisition method employed to analyse the lesions. Most of the computer-processed morphometric variables useful in automated diagnosis are not recognizable nor can be objectively evaluated by the human eye, except that of lesion dimension. However, several questions should be answered before assessing the actual usefulness, including the potential and limitations, of computer-based diagnostic procedures. The purpose of this study was to briefly review the different kinds of instrumentation being used to diagnose melanoma, and to raise questions and whenever possible provide answers in an attempt to establish whether there will be a future for these computerized systems.

Clinical and dermatoscopic diagnosis of early amelanotic melanoma.

Amelanotic cutaneous melanoma (ACM) often defies clinical diagnosis because of the lack of pigmentation. In an attempt to find diagnostic clues, we retrospectively studied the clinical features of 15 thin (< 1 mm thick or Clark level I) ACM lesions. The clinical features of early ACMs are identified and illustrated to enable early diagnosis and cure of these lesions. The typical early lesion presents as an asymmetric macula, which may be uniformly pinkish or reddish or, more often, has faint light pigmentation (tan, brown or grey) at the periphery; it has borders that may be well- or ill-defined. In our study, these features suggested the correct clinical diagnosis in only a minority (40%) of cases. Nine cases in this series were also subjected to dermatoscopy. By this technique we identified, as constant feature, the presence of small red dots, evenly distributed or grouped on a whitish or pink-red background. Our results show the importance of dermatoscopy in the evaluation of equivocal pink or reddish lesions. Red dots seen with this technique can be an important sign for the diagnosis of thin ACM. Since this sign does not appear to be pathognomonic, the presence of an associated pigmentary network can be decisive in the differential diagnosis.

A phantom with tissue-like optical properties in the visible and near infrared for use in photomedicine.

BACKGROUND AND OBJECTIVE: Modeling of light transport in tissue requires development of theoretical models and experimental procedures, as well as tissue-simulating phantoms. Our purpose was to develop a phantom that matches the optical characteristics of human skin in the visible and near infrared spectral range. STUDY DESIGN/MATERIALS AND METHODS: The phantom consists of a transparent silicone rubber in which Al(2)O(3) particles and a cosmetic powder are embedded. Layers with thickness as thin as 0.1 mm can be made. The optical properties of Al(2)O(3) particles and cosmetic powder, i.e., total attenuation, absorption and scattering coefficients, and phase function, have been determined in the visible and near infrared spectral range, by using direct and indirect techniques. RESULTS: By varying the concentration of scattering and absorbing particles, tissue-like layers can be produced with predictable optical properties. In particular, mixing at suitable concentration Al(2)O(3) particles and cosmetic powder with the silicone rubber, the optical properties of human skin have been simulated over a range of wavelengths from 400 to 1,000 nm. The comparison between the phantom diffuse reflectance spectrum and that of human skin, averaged over a sample of 260 patients, showed a good agreement. CONCLUSION: The proposed technique allows to produce a stable and reproducible phantom, with accurately predictable optical properties, easy to make and to handle. This phantom is a useful tool for numerous applications involving light interaction with biologic tissue.

Multispectral imaging approach in the diagnosis of cutaneous melanoma: potentiality and limits.

In an attempt to overcome the subjectiveness of clinical observation in the diagnosis of cutaneous melanoma, a computerized method is proposed. Reflectance images of 237 pigmented lesions (67 melanomas and 170 non-melanomas) were analysed using a telespectrophotometric technique. This device consists of a CCD camera with 17 interference filters. Images were acquired at selected wavelengths, from 420 to 1040 nm. Morphological and reflectance related parameters were extracted from the wavelength-dependent images of the lesions. The most significant features in the comparison between benign and malignant lesions were: lesion dimension (P < 10(-8) at 578 nm); mean value (P < 10(-7) at 940 nm) and standard deviation (P < 10(-4) at 904 nm) of lesion reflectance; lesion roundness (P < 10(-5) at 461 nm); and border irregularity (P < 10(-4) at 461 nm). Based on these parameters, a discriminant function between the two populations of lesions (naevi and melanomas) was obtained. By using the results of the analysis of the recruited lesions as 'training data', discriminant functions enabled the assignment of a score, or a 'risk probability', to each studied lesion. By imposing a sensitivity of 80% (a figure that mimics the diagnostic capability of an experienced clinician), entering or not entering the lesion dimension as input data in the discriminant analysis led to a specificity of 51% or 46% respectively. The high number of false-positive cases, which is a consequence of the selection criteria of the lesions, is, at present, the major limitation of the current technique. Nevertheless, our results suggest that an imaging-based computer-assisted device could be capable of discriminating malignant lesions mainly by evaluation of reflectance, especially in the infrared region, and shape properties. The dimension of a lesion should not be essential in the diagnosis of melanoma and, in our opinion, small melanomas should be recognized by a computer system as well as they are on clinical grounds.

Perceptual and response bias in unilateral neglect: two modified versions of the milner landmark task.

Perceptual and response bias in estimating the proportion of the two segments of prebisected lines were disambiguated in a group of 121 patients suffering from left neglect by means of two variants of the Milner Landmark task (Milner et al., 1993). The first variant, LANDMARK-V, required a verbal response; the second variant, LANDMARK-M, required manual pointing. The paper reports and discusses the results obtained on each task and their correlations, as well as the relationships between either kind of bias and the intrahemispheric location of the lesion. It is argued that besides their usefulness as a diagnostic tool the proposed variants of the Milner Landmark task provide results that are worth further investigation in their own right.

The effect of cytological screening on cervical neoplasia in the Italian province of Varese.

In the Varese province (409,142 female inhabitants in 1981), which has been covered by a cancer registry since 1976, cytologic screening for cervical cancer began in the early sixties in the municipality of Busto Arsizio (41,818 female inhabitants in 1981) and subsequently spread to the rest of the province. The distribution by age of cytologic smears and of detected in situ cancer reveals a more frequent attitude to be screened for women aged between 25 and 54 years. Overall, the incidence rate (world standardized) for invasive cancer in the province decreased from 10.3/100,000 women-year in the period 1976-81 to 7.5/100,000 in 1982-87. In Busto Arsizio a survey of the hospital archives has been carried out to identify the cases of cervical cancer diagnosed from 1966 to 1985: in this 20-year period, the incidence of cervical cancer decreased markedly, but only in those ages frequently screened. In the rest of the province, for the first period of cancer registration (1976-81), the incidence was significantly higher than in Busto Arsizio, especially for ages 35-64. Subsequently, between 1982-87, the cervical cancer incidence was low in both areas. For the period 1976-87, no difference for carcinoma in situ registration rates was observed between the two populations studied. Actually by 1976, when the Lombardy Cander Registry began its activity, the screening was diffuse throughout the province. These observations are consistent with the preventive effect of screening activity.

[Cervical thymic cysts. A clinical case report]. / Le cisti timiche cervicali. Presentazione di un caso clinico.

The presence of thymic residues in a laterocervical site is very rare, as is cystic degeneration. The paper reports the case of a six-year-old boy who presented a swelling in a left laterocervical site; preoperative tests (especially echography and fine needle aspiration) identified the cystic nature of the swelling which was then confirmed intraoperatively; histological test diagnosed a thymic cyst. The paper analyses the embryological, anatomopathological and clinical aspects of these formations and underlines the difficulty of making a differential diagnosis from other neck pathologies, especially branchial cysts. In conclusion, preoperative tests can only determine the cystic component but not the thymic origin of these formations which can only be confirmed by final histological tests.

[Comparative study of the effects of famotidine and omeprazole in the prevention of the aspiration of gastric contents syndrome in elective surgery]. / Studio comparativo degli effetti della famotidina e dell'omeprazolo nella profilassi della sindrome da aspirazione di contenuto gastrico in chirurgia elettiva.

This study compares the efficacy of omeprazole and famotidine in reducing gastric volume and activity. Sixty patients scheduled to undergo elective orthopaedic surgery were randomly allocated to receive famotidine 40 mg or omeprazole 40 mg at 22 hours, the night before surgery, or omeprazole at 22 hours the night before and 20 mg at 6 hours on the morning of surgery, 20 patients served as control and received no drugs. Intragastric volume and pH were measured immediately after induction anaesthesia and after surgery. Either drug reduces gastric volume. Famotidine reduces at maximum volume. Omeprazole reduces at maximum pH. Omeprazole 40 mg in some cases doesn't sufficiently reduced pH, because the interval from drug administration to induction of anaesthesia is too long. The comparably high volume of gastric content after omeprazole in single or double dose doesn't represent a risk.