Vaginal microbiome and metabolome highlight specific signatures of bacterial vaginosis.

In this study, we sought to find novel bacterial and metabolic hallmarks for bacterial vaginosis (BV). We studied the vaginal microbiome and metabolome of vaginal fluids from BV-affected patients (n = 43) and healthy controls (n = 37) by means of an integrated approach based on quantitative polymerase chain reaction (qPCR) and proton nuclear magnetic resonance ((1)H-NMR). The correlations between the clinical condition and vaginal bacterial communities were investigated by principal component analysis (PCA). To define the metabolomics signatures of BV, 100 discriminant analysis by projection on latent structure (PLS-DA) models were calculated. Bacterial signatures distinguishing the health condition and BV were identified by qPCR. Lactobacillus crispatus strongly featured the healthy vagina, while increased concentrations of Prevotella, Atopobium and Mycoplasma hominis specifically marked the infection. (1)H-NMR analysis has led to the identification and quantification of 17 previously unreported molecules. BV was associated with changes in the concentration of metabolites belonging to the families of amines, organic acids, short chain fatty acids, amino acids, nitrogenous bases and monosaccharides. In particular, maltose, kynurenine and NAD(+) primarily characterised the healthy status, while nicotinate, malonate and acetate were the best metabolic hallmarks of BV. This study helps to better understand the role of the vaginal microbiota and metabolome in the development of BV infection. We propose a molecular approach for the diagnosis of BV based on quantitative detection in the vaginal fluids of Atopobium, Prevotella and M. hominis, and nicotinate, malonate and acetate by combining qPCR and (1)H-NMR.

Botulinum toxin treatment in glaucomatous patients: a pilot study.

PURPOSE: The purpose was to evaluate the efficacy of the treatment of iatrogenic entropion (IE), in patients affected by primary open angle glaucoma (POAG), by botulinum toxin injections (BTI). PATIENTS AND METHODS: 20 patients of the "Glaucoma Center" of the Hospital "Umberto I" (Rome) were examined. These patients had POAG and used prostaglandin analogues (PA). Mean age was 75.5 years old (range 68-83); they had been suffering from PAOG since 10 years and were not affected by other relevant systemic diseases. One to three BTI were made into the lower orbicularis muscle using a 0.3 G needle (0.025 to 0.05 units for each injection site). RESULTS: The results were particularly significant in 18 out of 20 patients. Two patients showed slight improvements. A rating scale ranging from 0 to 6 points (0 corresponded to 'no effect' and 6 to the 'complete' resolution of the entropion) was used to evaluate the goals of the treatment. The average rating was 5.37 points. CONCLUSIONS: The entropion due to glaucoma therapy with PA can be successfully treated with BTI in the orbicularis muscle, despite offering temporary therapeutic effects.

Interpretable deep learning as a means for decrypting disease signature in multiple sclerosis.

Objective.The mechanisms driving multiple sclerosis (MS) are still largely unknown, calling for new methods allowing to detect and characterize tissue degeneration since the early stages of the disease. Our aim is to decrypt the microstructural signatures of the Primary Progressive versus the Relapsing-Remitting state of disease based on diffusion and structural magnetic resonance imaging data.Approach.A selection of microstructural descriptors, based on the 3D-Simple Harmonics Oscillator Based Reconstruction and Estimation and the set of new algebraically independent Rotation Invariant spherical harmonics Features, was considered and used to feed convolutional neural networks (CNNs) models. Classical measures derived from diffusion tensor imaging, that are fractional anisotropy and mean diffusivity, were used as benchmark for diffusion MRI (dMRI). Finally, T1-weighted images were also considered for the sake of comparison with the state-of-the-art. A CNN model was fit to each feature map and layerwise relevance propagation (LRP) heatmaps were generated for each model, target class and subject in the test set. Average heatmaps were calculated across correctly classified patients and size-corrected metrics were derived on a set of regions of interest to assess the LRP contrast between the two classes.Main results.Our results demonstrated that dMRI features extracted in grey matter tissues can help in disambiguating primary progressive multiple sclerosis from relapsing-remitting multiple sclerosis patients and, moreover, that LRP heatmaps highlight areas of high relevance which relate well with what is known from literature for MS disease.Significance.Within a patient stratification task, LRP allows detecting the input voxels that mostly contribute to the classification of the patients in either of the two classes for each feature, potentially bringing to light hidden data properties which might reveal peculiar disease-state factors.

A multi-perspective view of genetic variation in Cameroon.

In this study, we report the genetic variation of autosomal and Y-chromosomal microsatellites in a large Cameroon population dataset (a total of 11 populations) and jointly analyze novel and previous genetic data (mitochondrial DNA and protein coding loci) taking geographic and cultural factors into consideration. The complex pattern of genetic variation of Cameroon can in part be described by contrasting two geographic areas (corresponding to the northern and southern part of the country), which differ substantially in environmental, biological, and cultural aspects. Northern Cameroon populations show a greater within- and among-group diversity, a finding that reflects the complex migratory patterns and the linguistic heterogeneity of this area. A striking reduction of Y-chromosomal genetic diversity was observed in some populations of the northern part of the country (Podokwo and Uldeme), a result that seems to be related to their demographic history rather than to sampling issues. By exploring patterns of genetic, geographic, and linguistic variation, we detect a preferential correlation between genetics and geography for mtDNA. This finding could reflect a female matrimonial mobility that is less constrained by linguistic factors than in males. Finally, we apply the island model to mitochondrial and Y-chromosomal data and obtain a female-to-male migration Nnu ratio that was more than double in the northern part of the country. The combined effect of the propensity to inter-populational admixture of females, favored by cultural contacts, and of genetic drift acting on Y-chromosomal diversity could account for the peculiar genetic pattern observed in northern Cameroon.

The combined effect of surgeon and hospital volume on health outcomes: a systematic review.

OBJECTIVES: To explore the interaction between surgeon volumes (SVs) and hospital volumes (HVs) on health outcomes. MATERIALS AND METHODS: We searched MEDLINE, Embase, CINAHL, Web of Science as of May 2017. We included studies investigating the interaction between high or low SVs operating in high or low HVs. Review process follows the PRISMA guidelines. We assessed the methodological quality of the included studies using validated critical appraisal checklists. RESULTS: Sixteen studies were included. Due to the heterogeneity of studies, it was not possible to perform a quantitative analysis. Heath outcome are worse when high SV operating in low HV vs high HV, for the majority of the conditions (colorectal cancer, cystectomy, liver resection, mitral valve surgery, pancreatico-duodenectomy). Results for low SV are better when operating in high HV vs low HV for patients undergoing pancreatic-duodenectomy for mortality, 30 days complications and length of stay. Results for low SV are worse vs high SV when operating in high HV for most considered conditions. Results were in favour of higher SV vs low SV when operating in low HV for digital replantation success after injuries, 30 days mortality and complications after pancreatic-duodenectomy. CONCLUSIONS: The available evidence is limited. It is necessary to increase the monitoring of the association between surgeons volumes and hospitals volumes in which they operate, to ensure fairness and accuracy of care for better health outcomes.

Rich context information for just-in-time adaptive intervention promoting physical activity.

Sedentary lifestyle and inadequate levels of physical activity represent two serious health risk factors. Nevertheless, within developed countries, 60% of people aged over 60 are deemed to be sedentary. Consequently, interest in behavior change to promote physical activity is increasing. In particular, the role of emerging mobile apps to facilitate behavior change has shown promising results. Smart technologies can help in providing rich context information including an objective assessment of the level of physical activity and information on the emotional and physiological state of the person. Collectively, this can be used to develop innovative persuasive solutions for adaptive behavior change. Such solutions offer potential in reducing levels of sedentary behavior. This work presents a study exploring new ways of employing smart technologies to facilitate behavior change. It is achieved by means of (i) developing a knowledge base on sedentary behaviors and recommended physical activity guidelines, and (ii) a context model able to combine information on physical activity, location, and a user's diary to develop a context-aware virtual coach with the ability to select the most appropriate behavior change strategy on a case by case basis.

Intracameral epinephrine without the addition of intracameral lidocaine in the management of tamsulosin associated intraoperative floppy iris syndrome.

OBJECTIVE: Intracameral mydriatics using epinephrine associated with lidocaine have been reported as efficacious in reducing intraoperative floppy iris syndrome (IFIS) complications during cataract surgery. The aim of this study was to verify the efficacy of intracameral epinephrine without intracameral lidocaine as prophylaxis against IFIS in patients on tamsulosin. MATERIALS AND METHODS: This was a retrospective study on the results of cataract surgery in 18 patients on therapy with tamsulosin. Patients had undergone routine phacoemulsification in one eye. Successively, they underwent phacoemulsifcation in the fellow eye using non preserved intracameral epinephrine 1:4000 diluted with BSS. Intraoperative complications during cataract surgery had been documented and IFIS was graded based on iris billowing, miosis or iris prolapse. Follow-up was 3 months. RESULTS: Thirty-six eyes of 18 patients were included in the evaluation. The incidence of IFIS was significantly higher in the eyes where routine phacoemulsificaton had been performed (100%) with respect to eyes where phacoemulsification was carried out using intracameral epinephrine (33%) (Chi Square test =15.12, p<0.001). In routine phacoemulsification 16 eyes showed iris billowing, 14 eyes had some extent of miosis and 14 eyes had tendency to iris prolapse. In phacoemulsification with the use of intracameral epinephrine 5 eyes showed iris billowing, 4 eyes presented some extent of miosis and 2 eyes had tendency to iris prolapse. There were no serious intraoperative complications. CONCLUSIONS: Intracameral epinephrine without the addition of lidocaine was efficacious in the management of IFIS in patients on tamsulosin.

Human Y-chromosome variation in the western Mediterranean area: implications for the peopling of the region.

Y-chromosome variation was analyzed in a sample of 1127 males from the Western Mediterranean area by surveying 16 biallelic and 4 multiallelic sites. Some populations from Northeastern Europe and the Middle East were also studied for comparison. All Y-chromosome haplotypes were included in a parsimonious genealogic tree consisting of 17 haplogroups, several of which displayed distinct geographic specificities. One of the haplogroups, HG9.2, has some features that are compatible with a spread into Europe from the Near East during the Neolithic period. However, the current distribution of this haplogroup would suggest that the Neolithic gene pool had a major impact in the eastern and central part of the Mediterranean basin, but very limited consequences in Iberia and Northwestern Europe. Two other haplogroups, HG25.2 and HG2.2, were found to have much more restricted geographic distributions. The first most likely originated in the Berbers within the last few thousand years, and allows the detection of gene flow to Iberia and Southern Europe. The latter haplogroup is common only in Sardinia, which confirms the genetic peculiarity and isolation of the Sardinians. Overall, this study demonstrates that the dissection of Y-chromosome variation into haplogroups with a more restricted geographic distribution can reveal important differences even between populations that live at short distances, and provides new clues to their past interactions.

The lower susceptibility to Plasmodium falciparum malaria of Fulani of Burkina Faso (west Africa) is associated with low frequencies of classic malaria-resistance genes.

The gene frequencies in 1993-94 for haemoglobin S, haemoglobin C, alpha-3.7 deletional thalassaemia, G6PDA-, HLAB*5301 were estimated in Fulani, Mossi and Rimaibé ethnic groups of Burkina Faso, West Africa. The aim of the study was to verify whether the previously reported Fulani lower susceptibility to Plasmodium falciparum malaria was associated with any of these malaria-resistance genes. Similar frequencies for haemoglobin S were recorded in the 3 ethnic groups (0.024 +/- 0.008, 0.030 +/- 0.011, 0.022 +/- 0.013; in Mossi, Rimaibé and Fulani, respectively). The Mossi and Rimaibé showed higher frequencies when compared to Fulani for haemoglobin C (0.117 +/- 0.018, 0.127 +/- 0.020, 0.059 +/- 0.020), alpha-3.7 deletional thalassaemia (0.227 +/- 0.040, 0.134 +/- 0.032, 0.103 +/- 0.028), G6PDA- (0.196 +/- 0.025, 0.187 +/- 0.044, 0.069 +/- 0.025) and HLA B*5301 (0.189 +/- 0.038, 0.202 +/- 0.041, 0.061 +/- 0.024). Among Fulani the proportion of individuals not having any of these protective alleles was more than 3-fold greater than in the Mossi-Rimaibé group (56.8% vs 16.7%; P < 0.001). These findings exclude the involvement of these genetic factors of resistance to P. falciparum in the lower susceptibility to malaria of Fulani. This evidence, in association with the previously reported higher immune reactivity to malaria of Fulani, further supports the existence in this ethnic group of unknown genetic factor(s) of resistance to malaria probably involved in the regulation of humoral immune responses.

Element concentrations and cataract: an experimental animal model.

The determination of inorganic ions in cataractous human lenses has been the subject of several investigations; nevertheless, few studies have been concerned with trace element contents in lenses, and data are sometimes contradictory. An animal experimental model of induced cataract is here proposed with the aim of evaluating the changes of Ca, Na, K, Cu and Zn concentrations. The cataract was produced by an Nd:YAG Laser treatment of the right eye of sexteen male rabbits. The determination of the elements was performed by atomic absorption spectrometry (both flame and flameless methods) after an acid digestion of samples. Compared with the results obtained in left lenses used as a control (Ca 14.4+/-5.7 mg/kg d.w.; Na 1.3+/-0.5 g/kg d.w.; K 9.9+/-1.1 g/kg d.w.; Cu 0.24+/-0.09 mg/kg d.w.; Zn 24.8+/-2.3 mg/kg d.w.), the mean concentration values of opaque lenses showed some significant changes for Ca, Na, and Cu (Ca 123.7+/-106.6 mg/kg d.w.; Na 4.5+/-4.3 g/kg d.w; Cu 0.43+/-0.21 mg/kg d.w.). Potassium showed a tendency to decrease, and zinc to increase. Positive correlations were found between calcium and sodium both in controls (r=0.73, p<0.001) and in treated lenses (r= 0.87, p<0.0001). An inverse correlation between Ca and K confirmed the tendency of potassium to decrease.

[Glaucoma as a cause of blindness]. / Il glaucoma come causa di cecità.

The problem of glaucoma as a cause of blindness is discussed. WHO has proposed five classes of sightlessness on the sole basis of visual acuity without taking into account sense of luminosity, peripheral vision, color vision. In addition, different nations have different tables for evaluating the severity of the handicap so that data on this subject cannot be compared. This is why the problem of blindness due to glaucoma is very complicated and the concept of blindness has to be standardized as well as the method of epidemiologic research. The investigation starts from a list of the most reliable sources: records of associations of sightless subjects, lists of sightless persons receiving an invalidity pension, filed research, records of support activities and transversal population studies. This is followed by a general review of causes of blindness worldwide, their prevalence according to age and sex, and especially the causes of blindness in various nations and in different regions of Italy. Last, the percentage of loss of eye-sight due to glaucoma is examined.

[The epidemiologic problem of glaucoma]. / Il problema epidemiologico del glaucoma.

The problem of glaucoma is considered from an epidemiological point of view. The main causes of this pathology are discussed as well as present difficulties of effective prevention.

[Ocular pathology in HIV infection]. / Patologia oculare nell'infezione da HIV.

The above short note underscores the importance of ocular complications in HIV infection. These syndromes are either isolated or concomitant with CNS involvement but frequently they do not receive due consideration.

[Apropos of preventive ophthalmologic interventions in the child population of compulsory school age. Authors' experience]. / A proposito degli interventi sanitari oftalmologici di prevenzione nella scuola dell'obbligo. Una nostra esperienza.

The results are reported of work carried out during the last five years by the Center of Social Ophthalmology, director Prof. G. Scuderi, which is part of the II Division of the Ophthalmologic Clinic of Rome University "La Sapienza" with the object of trying out together with territorial units a model of preventive intervention acting as a filter for specialized university facilities. In other words, already existing facilities and medical personnel were to be used and trained for specific methods and techniques. From 1985 through 1990, 787 children selected by ophthalmologic screening by school doctors among the compulsory school population of the RM 3 and 5 districts were seen and submitted to periodic checks. This cohort included children aged 5 to 14 without significant differences in sex distribution and with prevalence of the 8 to 10 year olds. Each subject was submitted to complete eye examination including refractometry and orthoptics, color vision, biomicroscopic and ophthalmoscopic examination. The principal findings show that about 36% of subjects examined have a natural vision of 11/10 while the high percentage of ametropia observed was mainly represented by astigmatism and hypermetropy, albeit of minor intensity. Strabismus was found in 2.79% and implied marked visual deficit that was often refractory to any type of treatment. In addition, the prevalence was determined of other abnormalities concerning eye motility, color vision and pathologies involving anterior segment and eyeground. In their conclusion, the authors stress the rarity of organic ocular pathology in children (mostly represented by inflammatory changes of the adnexes and conjunctiva) whereas amblyopia was one of the main causes of visual deficit in children. They stress the importance of early therapeutic intervention in order to allow complete visual rehabilitation. The results of the clinical model for prevention were excellent so that it can even be proposed for large scale prevention of amblyopia.

Recent trends of ophthalmic diseases in Italy: are official data reliable?

PURPOSE: The aim of the study was to investigate the epidemiological trends of ocular diseases using hospital discharge forms as our data source. MATERIALS AND METHODS: We examined official Italian Statistical Institute (ISTAT) data concerning patients discharged from ophthalmologic wards. Our analysis was limited to the years when ISTAT managed health service data (1986, 1990 and 1994); whilst currently this duty has been transferred to the Ministry of Health. RESULTS: The diseases encountered most frequently were cataract, glaucoma and retinal detachment. Patients over 65 years of age represented 54% in 1986 and 67% in 1994. We observed a general trend toward shorter hospital stays (10.5 days in 1986 and 6.4 days in 1994). We applied an indirect analysis that included masculinity and chi 2 homogeneity that were aimed to evaluate results de spite the questionable reliability of ISTAT gross data. CONCLUSIONS: The results of indirect analysis (masculinity and chi 2 homogeneity, of data combined with the significant number of charts presenting incomplete diagnostic information strongly question the reliability of official documentation. The increase of hospitalisation for ophthalmic surgery and a higher average age of affected subjects were confirmed. We observed a reduction of mean hospital stay per admission, indicating a positive achievement in terms of cost reduction.

[Parameters for the assessment of inflammation of the anterior segment of the eye]. / Parametri per la valutazione delle flogosi del segmento anteriore dell'occhio.

The authors examine general aspects of the assessment and evaluation of inflammation of the anterior segment of the eye, stressing above all the importance of accurate history taking and correct diagnostic approach. The also define general features of inflammatory processes and analyse the main and most modern instrumental techniques that are essential for precise assessment of clinical parameters of inflammatory conditions of the anterior segment of the eye.

MTHFR C677T mutation, factor II G20210A mutation and factor V Leiden as risks factor for youth retinal vein occlusion.

OBJECTIVE: To determine whether methylene tetrahydrofolate reductase (MTHFR) C677T mutation, factor II G20210A mutation and factor V Leiden are risk factors for retinal vein occlusion (RVO) in patients under fifty years of age. METHODS: Comparison of 29 patients, under 50 years old of age, as affected RVO and 62 age matched normal controls. Plasma MTHFR C677T genotype, Factor II G20210A genotype, Factor V Leiden genotype, S protein level, C protein level, APCR presence (Actived Protein C Resistance), homocysteine level and Beta-thromboglobulin level were determined. RESULTS: Seventeen RVO patients and twenty-one controls were heterozygous for the MTHFR C677T mutation. Three RVO patients and twenty-three controls were homozygous for the MTHFR C677T mutation. Three RVO patients and two controls were heterozygous for the factor II G20210A mutation. One control was heterozygous for the factor V Leiden. CONCLUSIONS: This study fails to demonstrate that these mutations are risk factors for RVO in patients under fifty years of age.

[Minimal lesion hypertensive retinopathy and arterial pre-hypertension: evidence of arterial pressure monitoring in presumed normotensive subjects at zero risk]. / Retinopatia tensiva a lesioni minime e pre-ipertensione arteriosa: evidenze dal monitoraggio della pressione arteriosa in soggetti reputati normotesi a rischio zero.

The present study investigates the blood pressure (BP) 24 h pattern in 25 subjects who were found to show some incipient signs of hypertensive retinopathy, although they were diagnosed as normotensive by means of casual sphygmomanometry. BP was controlled by means of non invasive ambulatory monitoring. A comparable number of normotensive subjects without fundoscopic signs of hypertensive retinopathy was investigated as a control group. BP times series were analyzed by means of conventional and rhythmometric biometry. The biometric estimates suggest that the subjects with incipient hypertensive retinopathy show a significantly higher level of daily systolic BP even though their BP values remain below the reference limits. This finding suggests that the hypertensive retinopathy may exist in a non-zero stage characterizable as minimal change tensive retinopathy. This retinal picture occurs in subjects who show a pre-hypertensive stage in their BP 24 h pattern.

[The concept of "preclinical arterial hypertension" - in light of non-invasive, ambulatory blood pressure monitoring]. / Il concetto di "pre-ipertensione arteriosa" alla luce del monitoraggio ambulatorio non-invasivo della pressione arteriosa.

In clinical medicine it is possible to find subjects who show initial signs of hypertensive damage being normotensive at the "casual" sphygmomanometry. In order to verify whether or not these subjects are "true normotensives", it was applied the noninvasive ambulatory monitoring of blood pressure (BP). Five studies were performed: I. Normotensives with initial hypertensive retinopathy; II. normotensives with initial hypertensive cardiohypertrophy; III. Normotensives with initial hypertensive cardiohypertrophy of the transplanted heart; IV. Normotensive pregnant women with altered uterine blood flow; V. Normotensive pregnant women with intrauterine growth retardation. From all the studies, it was possible to derive that the subjects were all true normotensive. However, they were characterized by BP values on average higher than those of their controls, but below the reference limits given by WHO. Because of the relative elevation of BP, it was possible to argue that there exists a BP regimen which is potentially dangerous for the target organs, even though there is no evidence of manifest arterial hypertension. Such a hemodynamic condition causing hypertensive cardiovascular damage was defined "arterial pre-hypertension".

Positive emotional arousal increases duration of memory traces: different role of dopamine D1 receptor and ß-adrenoceptor activation.

We investigated the effects of post-training administration of dopamine D1 receptor antagonist SCH 23390 and ß-adrenergic receptor antagonist Propranolol on memory retention of an object sampled in a state of positive emotional arousal. Saline-treated mice trained and tested under high emotional/motivational arousal (High) showed discrimination of a novel object both 24 and 96 h post-training. Instead, mice trained and tested under low motivational arousal (Low) were unable to discriminate the novel object 96 h post-training. Both a high (2 mg/kg) and a low (1 mg/kg) dose of Propranolol reduced object discrimination in High mice tested 24 h post-training, whereas neither dose was effective in Low mice. A high dose of SCH 23390 (0.025 mg/kg) reduced discrimination of the novel object in High mice tested both 24 and 96 h post-training, whereas a low dose of the D1 antagonist (0.01 mg/kg) reduced discrimination in High mice tested 96 h post-training and abolished discrimination in Low mice tested 24h after training.