Retraction Note: Autoantibodies detection in patients affected by autoimmune retinopathies.

The article "Autoantibodies detection in patients affected by autoimmune retinopathies", by M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Issues with ethical approval -       Undeclared conflict of interest In light of concerns regarding the potential manipulation of Supplementary Figure 2, the journal's inquiry has been unable to conclusively determine whether the alterations noted on PubPeer constitute figure manipulation. The investigation yielded divergent evaluations. However, given the aforementioned concerns, the Editor in Chief doubts the integrity of the findings presented and thus, has opted to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34690.

Autoantibodies detection in patients affected by autoimmune retinopathies.

OBJECTIVE: Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported. PATIENTS AND METHODS: In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera. RESULTS: Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409). CONCLUSIONS: AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis.

Thyroid-stimulating hormone levels in the first days of life and perinatal factors associated with sub-optimal neuromotor outcome in pre-term infants.

AIM: To identify perinatal factors associated with sub-optimal neuromotor outcome in infants without evident central nervous system lesions (intraventricular hemorrhage/ periventricular leukomalacia), with gestational age ≤30 (group I) and of 31-32 weeks (group II). PATIENTS AND METHODS: A total of 102 premature infants admitted to the Neonatal Intensive Care Unit of Pisa, at 26-32 weeks of gestation, were studied. Data about perinatal factors and TSH values at 3-4 days of life were collected. The assessment of neuromotor development was performed at 18 months of corrected age, using the locomotor subscale of the Griffiths Scales of Mental Development. RESULTS: Risk factors supposed to be predictive of sub-optimal neuromotor outcome (odds ratio >1) were at ≤30 weeks: male sex, small for gestational age, patent duct arterious, respiratory distress syndrome, and at 31-32 weeks: Apgar at 5 min <7, respiratory distress syndrome, patent duct arterious and birth weight <1500 g. A strong correlation was also found between TSH screening values >4,3 mU/l and suboptimal neuromotor outcome in both groups. CONCLUSIONS: Several perinatal factors, acting on an immature and more vulnerable nervous system, such as the pre-term one, different for different gestational ages, are associated with a sub-optimal neuromotor outcome. Higher, but within the normal range, TSH values at screening seem to be a strong risk factor for neuromotor outcome in preterm infants without intraventricular hemorrhage or periventricular leukomalacia.

PERG adaptation for detection of retinal ganglion cell dysfunction in glaucoma: a pilot diagnostic accuracy study.

It has been previously demonstrated that the adaptive phase changes of steady-state pattern electroretinogram (SS-PERG), recorded during 4-min presentation of patterned stimuli, are reduced in glaucoma suspects and patients compared to normal subjects. Our study aims at testing the hypothesis that adaptive changes of SS-PERG, recorded using the novel optimized Next Generation PERG (PERGx) protocol, differ between glaucoma patients and controls. In this pilot cross-sectional study, we included 28 glaucoma patients and 17 age-matched normal subjects. Both patients and controls underwent a full ophthalmologic examination, visual field testing, OCT and PERGx. The PERGx signal was sampled over 2 min (providing 1 noise and 9 signal packets) in response to alternating gratings generated on an OLED display. PERGx amplitude and phase were analyzed to quantify adaptive changes over recording time. Receiver operating characteristic (ROC) curves were used to study the diagnostic accuracy of PERGx parameters in distinguishing glaucoma patients from normal subjects. PERGx amplitude and phase data showed declining trends in both groups. PERGx amplitude slope and grand-average vector amplitude and phase were significantly different in patients compared to controls (p < 0.01), whereas phase angular dispersion was greater in patients but not significantly different between the two groups. The area under the ROC curves were 0.87 and 0.76 for PERGx amplitude slope and grand-average vector amplitude, and 0.62 and 0.87 for PERGx angular dispersion and grand-average vector phase, respectively. The PERGx paradigm resulted highly accurate in detecting the reduction of amplitude adaptive changes in glaucoma patients, presumably due to the loss of functional retinal ganglion cell autoregulation. Thus, PERG adaptation, recorded by this new protocol, might be helpful in the identification and diagnosis of early glaucomatous dysfunction.

Classification strategies for a single-trial binary Brain Computer Interface based on remembering unpleasant odors.

A Brain Computer Interface (BCI) is a useful instrument to support human communication. In recent years, BCI systems have been frequently implemented by using EEG. Regarding the communication paradigm used, there exists a very large number of strategies and, recently, the remembering of unpleasant odors has been also defined. However, the quality of the signals collected by this last paradigm is very poor, due to the absence of a real stimulus (the stimulus consists in remembering a disgusting situation). For this reason, a crucial node is the choice of a very efficient classification algorithm to improve the accuracy of the BCI. The present paper describes a and compares classification strategies for such type of BCI systems. The proposed methods and the experimental setup are described and experimental measurements are presented and discussed.

Nocturnal serum thyrotropin (TSH) surge and the TSH response to TSH-releasing hormone: dissociated behavior in untreated depressives.

TSH secretion, with particular regard to the nocturnal surge of the hormone, was evaluated in 15 women (age range, 35-66 yr; mean, 50 yr) with untreated major endogenous depression and 15 healthy women (age range, 32-67 yr; mean, 53 yr) using an ultrasensitive assay. Mean morning (0830 h) TSH values did not differ in the 2 groups (1.3 +/- 02 mU/L in depressives and 1.4 +/- 0.1 mU/L in controls), whereas mean nighttime (2400-0200 h) values were significantly reduced in depressives (1.5 +/- 0.3 vs. 3.1 +/- 0.3 mU/L; P less than 0.0005). At variance with the control group, morning and nighttime TSH values did not differ in the depressives. The nocturnal serum TSH surge was abolished in 14 of 15 depressed patients. The mean peak TSH value after TRH was slightly yet significantly lower in the depressives. Patients with subnormal (less than 0.4 mU/L) TSH values in the morning had a serum TSH increase after TRH less than 2 mU/L in 5 of 6 cases and a lack of the nocturnal TSH surge in 6 of 6. Among the 9 patients with normal TSH values in the morning, the nocturnal serum TSH surge was lost in 8 of 9, whereas the response to TRH was normal in all. The depressives, at variance with other reports, showed significantly lower values of total and free thyroid hormones. Mean serum sex hormone-binding globulin (SHBG) and ferritin were also significantly reduced. In conclusion, major endogenous depression is associated with a major impairment of TSH secretion, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal. In this regard, the loss of the nocturnal serum TSH rise would appear to be a more sensitive indicator of hypothalamus-pituitary-thyroid axis alterations in depressives than the TRH test, which is commonly used in the evaluation of these patients. The lack of the nocturnal TSH surge may be responsible for the reduced thyroid hormone secretion and supports the case for some degree of central hypothyroidism in endogenous depression.

Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels.

BACKGROUND: We have proposed a stress-diathesis model for suicidal behavior, in which major depression is a stressor and the diathesis is shared with aggression. Neurotransmitter correlates of the stress or diathesis have not been adequately evaluated by previous studies, because they did not simultaneously examine the relationship of multiple neurotransmitters to all three psychopathologies in the same population. In the present study we investigated the relationship of monoamine metabolites to aggressivity, suicidal behavior, and depression in patients with mood disorders. METHODS: Ninety-three drug-free subjects with a major depressive episode underwent lumbar puncture and psychiatric evaluation. Cerebrospinal fluid CSF levels of 5hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA) and methoxy-hydroxy-phenylglycol (MHPG) were assayed. The relationships between monoamine metabolites and clinical variables were statistically evaluated. RESULTS: Higher lifetime aggressivity correlated significantly with lower CSF 5-HIAA. Lower CSF 5-HIAA and greater suicidal intent were found in high-lethality suicide attempters compared with low-lethality suicide attempters. Low-lethality attempters did not differ biologically from nonattempters. No correlation between CSF HVA and any of the psychopathological variables was found. Only aggression showed a trend statistically in correlating positively with CSF MHPG levels. CONCLUSIONS: Lower CSF 5-HIAA concentration was independently associated with severity of lifetime aggressivity and a history of a higher lethality suicide attempt and may be part of the diathesis for these behaviors. The dopamine and norepinephrine systems do not appear to be as significantly involved in suicidal acts, aggression, or depression. The biological correlates of suicide intent warrant further study.

Anxiety in major depression: relationship to suicide attempts.

OBJECTIVE: This study was an examination of the relationship of lifetime panic disorder and anxiety symptoms at index hospitalization to a history of a suicide attempt in patients with a major depressive episode. METHOD: A total of 272 inpatients with at least one major depressive episode, with or without a history of a suicide attempt, were entered into the study. They were given structured diagnostic interviews for axis I and axis II disorders. Suicide attempt history, current psychopathology, and traits of aggression and impulsivity were also assessed. RESULTS: The rates of panic disorder did not differ in the suicide attempters and nonattempters. Agitation, psychic anxiety, and hypochondriasis were more severe in the nonattempter group. A multivariate analysis confirmed that this effect was independent of aggression and impulsivity. CONCLUSIONS: Comorbid panic disorder in patients with major depression does not seem to increase the risk for lifetime suicide attempt. The presence of greater anxiety in the nonattempters warrants further investigation.

The comparative efficacy and safety of carbamazepine versus lithium: a randomized, double-blind 3-year trial in 83 patients.

The comparative usefulness of carbamazepine and lithium carbonate in the acute and prophylactic management of DSM-III diagnosed major affective, schizoaffective, or schizophreniform psychoses was investigated in a 3-year, prospective double-blind randomized trial with 83 in- and outpatients. The incidence of side effects was similar in both treatment groups, and side effects generally responded well to dosage reduction. Both drugs were effective in two thirds of the patients and appeared about equal in most outcome measures, except for a significantly higher dropout rate for patients with mood-incongruent psychotic features who were assigned to the lithium group. Both drugs appeared more effective in preventing excited rather than depressive symptoms.

Kinetics of distribution of amphetamine in cats.

The distribution and metabolic fate of amphetamine were studied in cats. In the brain, high levels of drug were detected in the grey matter structures at short intervals after administration, while at longer intervals distribution between white and grey matter areas was more uniform. In peripheral tissues the greatest concentration of the drug was seen in the highly vascularized organs. Para-hydroxy-amphetamine was found in minimal amounts in the liver and kidneys and only at trace quantities in the brain.

Regional distribution of diazepam and its metabolites in the brain of cat after chronic treatment.

Repeated administration of diazepam leads to remarkable accumulation of N-desmethyldiazepam in white matter structures and in subcortical areas such as thalamus, hypothalamus, and hypophysis. Diazepam and the hydroxylated metabolites were present in lesser amounts. The distribution pattern of diazepam and N-desmethyldiazepam offers a rationale for its efficacy in inhibiting seizures spreading and for the lack of effect on primary foci discharges.

Renal tolerance of rubidium chloride: short-term clinical evaluation.

The rubidium and lithium ions are known to have opposite effects on a wide range of biochemical and behavioral parameters in experimental animals. Based on the proven effectiveness of lithium as an antimanic agent, several trials have been conducted with rubidium in the acute treatment of the depressive phase of bipolar illness. The results to date are promising. However, the 30- to 60-day biologic half-life of rubidium has mandated careful studies of potential toxicity before engaging in long-term administration of this ion to depressive subjects. One area of potential concern is the possibility of renal toxicity, which could be expressed as unexpectedly increased retention of rubidium. The data in this paper show that after 15 days of rubidium administration, there are no changes beyond the normal range in a variety of kidney function tests, including in four enzymes which are specific markers of tubule cell function.

Omega-space adaptive acquisition technique for magnetic resonance imaging from projections.

An omega-space adaptive acquisition technique for MRI from projections is presented. It is based on the evaluation of the information content of a set composed of four initial projections, measured at angles 0 degrees, 45 degrees, 90 degrees, and 135 degrees, followed by the selection of new angles where the information content is maximum. An entropy function is defined on the power spectrum of the projections that is useful for evaluating the information content of each projection. The method makes it possible to reduce the total acquisition time with little degradation of the reconstructed image and it adapts to the arbitrary shape of the sample. For this reason, it can be particularly useful in those applications where acquisition from projections is strongly recommended to save acquisition time, such as functional MRI, imaging of species having very short T(2), or angiography. The method has been tested both on simulated data and on experimental data collected by a commercial MRI apparatus. The method has also been compared to the regular acquisition method, that is, the standard acquisition method in MRI from projections.

Fourier reconstruction as a valid alternative to filtered back projection in iterative applications: implementation of Fourier spectral spatial EPR imaging.

The qualitative equivalence between the Fourier reconstruction (FR) algorithm and the filtered back projection (FBP) algorithm is demonstrated when all the different phase errors that can occur in FR are eliminated. The causes of phase errors are underlined and methods to eliminate them are presented. The practical comparison between FR and FBP has been evaluated on a numerical test image and the results are reported, demonstrating the qualitative equivalence. FR has the advantage of being very computationally efficient. In fact, the time spent to obtain the FR image was 1/20 of that used to obtain the FBP image. Because of the computational efficiency of FR and the good quality of the results obtained, an iterative version of FR has been used to implement the spectral-spatial imaging (SSI) algorithm in the field of electron paramagnetic resonance imaging (EPRI). An experimental example, demonstrating its good performance, is reported.

A prospective study of stability and change over 2 years of affective temperaments in 14-18 year-old Italian high school students.

OBJECTIVE: It is generally accepted that temperament is not entirely stable, and that it changes with development, particularly in juvenile subjects; also, some temperaments are believed to be inherently more unstable. There is a great deal of current interest in Kraepelin's thesis that temperamental dysregulation in juvenile subjects represents the constitutional foundation from which the more florid episodes of manic-depressive illness arise; the cyclothymic, hyperthymic, depressive and irritable temperaments under consideration might represent the first observable phenotypes of the genetic diathesis for bipolarity. The analyses on the temperamental attributes in juvenile subjects were undertaken within this theoretical framework. METHOD: We evaluated 206 Italian high school students (14-18 years old) by means of a semi-structured affective temperament interview (TEMPS-I) at T0 and T1 two years later. Age, sex and psychometric properties of TEMPS-I raw scale score and weighted cut-off (as specially weighted linear combination of items) were used as predictive variables of stability. RESULTS: Affective temperaments had a low to moderate level of stability, reaching 60% in the case of subjects with dominant cyclothymic temperament. The stability of the depressive temperament was primarily related to its weighted cut-off. The stability of the hyperthymic temperament appeared related to male sex, young age, and total scale score. Male sex represented the best stability predictor for the cyclothymic temperament as well. The group of subjects with an unstable depressive temperament showed a change toward the dominant cyclothymic temperament, whereas individuals with unstable hyperthymic temperamental traits moved on towards the dominant cyclothymic and depressive temperaments. The irritable construct was the least stable. LIMITATIONS: The infeasibility of a multiwave design represents the main limitation in evaluating the predictors of stability. Furthermore, in the present analyses, the size of the cyclothymic subsample was small. CONCLUSION: Our data indicate considerable fluctuation and instability in depressive and hyperthymic temperaments in mid-adolescence. The cyclothymic temperament appears to be the most stable. Interestingly, cyclothymic moodiness appears more persistent in juvenile males; likewise persistent hyperthymic traits appear more of a "male" attribute. CLINICAL AND PUBLIC HEALTH IMPLICATIONS: We submit that these sex-relevant traits could be important in the risk of developing juvenile bipolarity. Literature review indicates that clinical studies, albeit on small samples, have already provided some support for this thesis. Larger studies on epidemiological samples could be more informative from a public health perspective. A user-friendly affective temperament questionnaire, which is under development, is critical for the methodology of such studies. Our study indicates that the present version of the Akiskal-Malya questionnaire can be easily used post-pubertally. Age adjustment must be considered for younger subjects.

The semi-structured affective temperament interview (TEMPS-I). Reliability and psychometric properties in 1010 14-26-year old students.

BACKGROUND: The purpose of this study was to evaluate the reliability and psychometric properties of the Semistructured Affective Temperament Interview, and determine cut-offs for each temperament. METHOD: 1010 Italian students aged between 14 and 26 were evaluated by means of the Akiskal and Mallya criteria in a Semistructured Interview for depressive, cyclothymic, hyperthymic, and irritable temperaments. RESULTS: This instrument has very good reliability and internal consistency. The percentage of subjects with a z-score higher than the second positive standard deviation ( + 2 SD) on the scales of depressive and cyclothymic temperaments are 3.6% and 6.3% (reaching scores of 7/7 and 9/10), respectively. Hyperthymic traits, on the other hand, are widespread in our sample: most subjects are included within the second positive standard deviation ( + 2 SD), and 8.2% of these reach a 7/7 score; therefore, the problem of defining a cut-off for this temperament is still open. By contrast, the irritable temperament is rare, conforming to a non-gaussian distribution, with 2.2% of cases above the second positive standard deviation ( + 2 SD). LIMITATION: The data are based on subject report without collateral information and external validation. CONCLUSION: This study contributes to more accurate definition of cut-offs for individual temperament scales. The standardization of the interview thus makes it possible to compare three out of four temperamental scales, showing the dominant temperamental characteristics for each subject. Prospective studies are needed to demonstrate the stability of these traits over time.

Current issues in the identification and management of bipolar spectrum disorders in 'special populations'.

Bipolar disorder is a common, lifelong condition that can present during childhood, adolescence, adulthood or later in life. It may occur alone but, more frequently, is complicated by comorbid psychiatric and medical disorders. As such, bipolar disorder presents in many different special populations, each of which warrants specific considerations of diagnosis, treatment and management. This review summarizes common issues concerning recognition of bipolar disorder, particularly in younger patients, discusses the prevalence and treatment of anxious disorder and addictive comorbidity, and considers bipolar disorder in the institutionalized and forensic populations. Treatment options and the supporting evidence are discussed.

TEMPS-I: delineating the most discriminant traits of the cyclothymic, depressive, hyperthymic and irritable temperaments in a nonpatient population.

BACKGROUND: Although most personality constructs have been standardized in population studies, cyclothymic, depressive, irritable and hyperthymic temperaments putatively linked to mood disorders have been classically derived from clinical observations. METHODS: We therefore administered the semi-structured affective temperament schedule of Memphis, Pisa, Paris and San Diego, Interview version (TEMPS-I) -- in its original University of Tennessee operationalization -- to 1010 Italian students aged between 14 and 26. The interview, administered in a randomized format, took 20 min per subject. RESULTS: The semi-structured interview was easy to administer and well accepted by subjects, with no refusals. Principal component analysis with varimax rotation confirmed the hypothesized four-dimensional factor structure of the interview, with good to excellent internal consistency. Furthermore, discriminant analysis and multiple regression provided suggestions for identifying the traits that are most useful in defining a weighted cut-off for each of the temperaments (and which, with minor exceptions, are in agreement with those previously proposed on clinical grounds). In an additional exploratory factorial analysis, a depressive type which loads negatively on hyperthymia was distinguished from cyclothymia; the irritable temperament did not appear to have significant loading on either factor. LIMITATION: All the present analyses were internal to the scale itself, but ongoing studies are comparing them with other systems of temperament as well as testing their clinical cogency for affectively ill populations. CONCLUSION: While more work needs to be done on better operationalization of the irritable temperament, our findings overall support the existence -- in a relatively young nonpatient population -- of cyclothymic, depressive and hyperthymic types according to the classic descriptions of Kraepelin, Kretschmer and Schneider, in their TEMPS-I operationalization. CLINICAL IMPLICATIONS: Coupled with a previous report identifying 10% of the same 14-26-year-old nonpatient population meeting an empirically defined statistical cut-off for these temperaments, the present data define the putative 'fundamental states' that Kraepelin considered to be the personal predisposing anlagé of major affective disorders.

Dysthymia: clinical picture, extent of overlap with chronic fatigue syndrome, neuropharmacological considerations, and new therapeutic vistas.

Dysthymia, as defined in the American Psychiatric Association and International Classification of Mental Disorders, refers to a prevalent form of subthreshold depressive pathology with gloominess, anhedonia, low drive and energy, low self-esteem and pessimistic outlook. Although comorbidity with panic, social phobic, and alcohol use disorders has been described, the most significant association is with major depressive episodes. Family history is loaded with affective, including bipolar, disorders. The latter finding explains why dysthymia, especially when onset is in childhood, can lead to hypomanic switches, both spontaneously and upon pharmacologic challenge in as many as 30%. Indeed, antidepressants from different classes -tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMAs), selective serotonin-reuptake inhibitors (SSRIs) and, more recently, amisulpride, and spanning noradrenergic, serotonergic as well as dopaminergic mechanisms of action - have been shown to be effective against dysthymia in an average of 65% of cases. This is a promising development because social and characterologic disturbances so pervasive in dysthymia often, though not always, recede with continued pharmacotherapy beyond acute treatment. Despite symptomatic overlap of dysthymia with chronic fatigue syndrome - especially with respect to the cluster of symptoms consisting of low drive, lethargy, lassitude and poor concentration - neither the psychopathologic status, nor the pharmacologic response profile of the latter syndrome is presently understood. Chronic fatigue today is where dysthymia was two decades ago. We submit that the basic science - clinical paradigm that has proven so successful in dysthymia could, before too long, crack down the conundrum of chronic fatigue as well. At a more practical level, we raise the possibility that a subgroup within the chronic fatigue group represents a variant of dysthymia.

Involvement of serotonin system in bulimia.

Platelet 3H-imipramine binding was investigated in 8 patients affected by bulimia according to DSM III criteria, and in 7 healthy volunteers. The Bmax +/- SD (fmol/mg protein) was 356 +/- 53 in patients, and 1144 +/- 134 in controls. The Kd +/- SD (nM) was 1.35 +/- 0.44 in patients, and 1.90 +/- 0.72 in controls. There was a significant difference (p less than 0.0001) in Bmax values in the two groups, whereas no significant difference was observed in Kd values. This study suggests the possible involvement of the indoleamine system in bulimia.