Transient plasma viral rebound after SARS-CoV-2 vaccination in an exceptional HIV-1 elite controller woman.

BACKGROUND: Elite controllers are able to control viral replication without antiretroviral therapy. Exceptional elite controllers do not show disease progression for more than 25 years. Different mechanisms have been proposed and several elements of both innate and adaptive immunity are implicated. Vaccines are immune stimulating agents that can promote HIV-RNA transcription; transient plasma HIV-RNA detectability has been described within 7-14 days after different vaccinations. The most reliable mechanism involved in virosuppressed people living with HIV is a generalized inflammatory response that activates bystander cells harboring latent HIV. So far no data about viral load increase in elite controllers after SARS-CoV-2 vaccination are reported in literature. CASE PRESENTATION: We report the case of a 65-year-old woman of European ancestry, diagnosed with HIV-1/HCV co-infection more than 25 years ago. Since then, HIV-RNA remained undetectable and she never received ARV therapy. In 2021 she was vaccinated with mRNA-BNT162b2 vaccine (Pfizer-BioNTech®). She was administered with three doses in June, July and October 2021, respectively. The last available viral load was undetectable in March 2021. We observed an increase of VL at 32 cp/ml and 124 cp/mL, two and seven months after the second vaccine dose, respectively. During monthly follow-up, HIV-RNA gradually and spontaneously dropped becoming undetectable without ARV intervention. COVID-19 serology was positive with IgG 535 BAU/mL, showing response to vaccination. We measured total HIV-DNA at different time-points and we found it detectable both at the time of the higher plasma HIV-RNA (30 cp/10^6 PBMCs) and when it was undetectable (13 cp/10^6 PBMCs), in reduction. CONCLUSIONS: This case is the first report, to our knowledge, describing a rebound of plasma HIV-RNA in an elite controller after three doses of mRNA-BNT162b2 vaccine for SARS-CoV-2. Concomitantly with a spontaneous reduction of plasma HIV-RNA ten months after the third dose of mRNA-BNT162b2 vaccine (Pfizer-BioNTech®) without antiretroviral therapy intervention, we observed a reduction of total HIV-DNA in peripheral mononuclear cells. The potential role of vaccinations in altering HIV reservoir, even in elite controllers when plasma HIV-RNA is undetectable, could be a valuable aspect to take into account for the future HIV eradication interventions.

Psychogenic non-epileptic seizures and functional motor disorders in developmental age: A comparison of clinical and psychopathological features.

BACKGROUND: Psychogenic Non-Epileptic Seizures (PNES) and Functional Motor Disorders (FMDs) commonly represent the main clinical manifestations of Functional Neurological Disorders (FNDs). Despite their high prevalence in pediatric neurological services, literature on this topic is still spare for this population. The present study aimed to deepen the clinical knowledge of a pediatric FNDs sample through a demographic and clinical characterization of the most recurrent clinical patterns during the pediatric age. Moreover, a comparison of neuropsychological and psychopathological profiles of PNES and FMD patients was carried out to identify specific vulnerabilities and therapeutic targets linked with these different clinical manifestations. MATERIALS AND METHODS: A total of 43 FNDs patients (age range 7-17 years old) were retrospectively included in our study, enrolled in two subgroups: 20 with FMDs and 23 with PNES diagnosis. They were inpatients and outpatients referred over a period of 5 years and a standardized neurological, neuropsychological (WISC-IV/WAIS-IV), and psychiatric (CDI-2, MASC-2, ADES, DIS-Q, PID-5) evaluation was assessed. RESULTS: In PNES patients the most common clinical phenotypes were functional tonic-clonic (52%) and atonic (32%) manifestations while in the FMDs group were gait alterations (60%), functional myoclonus (35%), and tremor (35%). A higher frequency of cognitive impairment was reported in PNES patients with higher anxiety-depressive symptom rates than FMDs patients. CONCLUSIONS: Notably, specific neurocognitive and psychopathological profiles were described in PNES and FMDs, highlighting higher cognitive and psychiatric vulnerabilities in PNES, suggesting as well different strategy for therapeutic approaches.

Prevalence of Dirofilaria repens in dogs living in deltaic coastal plain of the Volturno River (Italy): a geographical risk model of infection.

The prevalence of vector-associated parasitic infections is high in central-southern Italy. The deltaic coastal plain of the Volturno River has been suspected, by veterinary practitioners, to have a high accidental incidence of Dirofilaria repens. Thus, the goal of this study was to evaluate the prevalence of dirofilariasis and other coinfections frequently described in dogs living in the Volturno area. Blood samples of 100 clinical asymptomatic dogs were examined using a Knott's technique and polymerase chain reaction in order to identify microfilariae. Other vector-borne coinfections were also investigated using ELISA kits. The results were analysed using statistical and Geographic Information System (GIS) software. Microfilariae of D. repens were detected in 10% of the dogs surveyed, with a presence of antibodies against Ehrlichia canis (4/10) and Dirofilaria immitis (1/10). Such high incidence should be considered in light of the zoonotic potential for D. repens and the support for more regular use of repellents to prevent the spread of this disease. The GIS analyses indicated that the study area provides suitable conditions to sustain populations of mosquito vectors and D. repens parasites throughout much of the year.

Antiretroviral concentrations in the presence and absence of valproic acid.

OBJECTIVES: An unexpected drug-drug interaction has been recently reported between dolutegravir, an HIV integrase inhibitor, and valproic acid. Despite there being several potential underlying mechanisms, plasma protein displacement has been suggested. The aim of this study was to assess plasma concentrations of several antiretrovirals when administered with or without valproic acid. METHODS: We performed a therapeutic drug monitoring registry analysis and identified patients concomitantly taking antiretrovirals and valproic acid and without clinical affecting conditions or interacting drugs. RESULTS: One hundred and thirty-four patients were identified. Median (IQR) age and BMI were 49.7 years (45-56) and 23.4 kg/m2 (20.8-26.3) and 78 were male (58.2%). Despite small groups, we observed no major effect on antiretroviral exposure, even when considering highly protein-bound compounds (such as etravirine), with the exception of dolutegravir trough concentrations [median (IQR) = 132 ng/mL (62-227) in individuals on valproic acid versus 760 ng/mL (333-1407) in those not receiving valproic acid]. CONCLUSIONS: Valproic acid does not have a major effect on antiretrovirals other than dolutegravir. The mechanism of this unexpected drug-drug interaction may be the combination of protein displacement, reduced absorption and CYP3A4 induction.

Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.

OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

Antimicrobial resistance gene shuffling and a three-element mobilisation system in the monophasic Salmonella typhimurium strain ST1030.

In this study we describe the genetic elements and the antimicrobial resistance units (RUs) harboured by the Salmonella Typhimurium monophasic variant 1,4,[5],12:i:- strain ST1030. Of the three identified RUs two were chromosomal, RU1 (IS26-blaTEM-1-IS26-strAB-sul2- IS26) and RU2 (IS26-tetR(B)-tetA(B)-ΔIS26), and one, RU3 (a sul3-associated class 1 integron with cassette array dfrA12-orfF-aadA2-cmlA1-aadA1), was embedded in a Tn21-derived element harboured by the conjugative I1 plasmid pST1030-1A. IS26 elements mediated the antimicrobial resistance gene (ARG) shuffling and this gave rise to pST1030-1A derivatives with different sets of ARGs. ST1030 also harboured two ColE1-like plasmids of which one, pST1030-2A, was mobilisable and the target of an intracellular translocation of the Tn21-derived element; the second (pST1030-3) was an orphan mob-associated oriT plasmid co-transferred with pST1030-1A and pST1030-2A. pST1030-2A and pST1030-3 also carried a parA gene and a type III restriction modification system, respectively. Overall analysis of our data reinforces the role played by IS26, Tn21-derived elements and non-conjugative plasmids in the spread of ARGs and supplies the first evidence, at least in Salmonella, for the identification of a natural isolate harbouring a three-element mobilisation system in the same cell.

[Stress fracture of the distal femoral growth plate in a young belgian table tennis champion]. / Fracture de fatigue du cartilage de croissance fémoral distal chez un jeune champion belge de tennis de table.

We report a rare type of stress fracture in a young athlete, great hope of belgian table tennis. Although this type of fracture is not rare in the broad sense of the term, a stress fracture located at the distal femoral physeal is exceptional. Such a complication must be quickly detected because of growth disorders and impact on sports performances that this may cause. On the basis of an anamnesis and detailed clinical observations, we describe the physiopathology as well as the diagnostic and therapeutic management of this pathology.

Nous présentons un type rare de fracture de fatigue chez un jeune sportif, grand espoir du tennis de table belge. Bien que ce type de fracture ne soit pas rare au sens large du terme, une fracture de fatigue située au niveau du cartilage de croissance fémoral distal est exceptionnelle. Cette complication doit être rapidement détectée vu les troubles de croissance et l'impact sur les performances sportives que cela peut engendrer. A partir d'une anamnèse et d'observations cliniques minutieuses, nous décrivons la physiopathologie ainsi que la prise en charge diagnostique et thérapeutique de cette pathologie.

Tenofovir disoproxil fumarate discontinuation for renal outcomes: any room for treatment personalization?

Tenofovir disoproxil fumarate (TDF) is a very effective antiviral drug that has been associated with tubular dysfunction. The aim of this study was to analyze the demographic, pharmacokinetic, and pharmacogenetic variables associated with TDF discontinuation for renal outcomes in stable HIV-positive patients using multivariable analyses. Three hundred and four patients were included (73% male, with median age and eCrCl of 45.3 years and 90.9 mL/min, respectively). After a median follow-up of 28.3 months, 27 patients discontinued TDF for renal adverse events [persistent urinary abnormalities (n = 21) or eCrCl < 60 mL/min (n = 6)] providing an incidence of 3.77 events per 100 patient-year. The probability of TDF discontinuation was higher with several features (male gender, older age, not Caucasians ancestry, absence of intravenous drug abuse, protease inhibitors, previous indinavir, HCV-positivity, lower CD4 cell count, detectable HIV-RNA, lower eCrCl, spot-urine proteinuria) and higher tenofovir concentrations but not genetic variants. Tenofovir plasma concentrations were prognostic of TDF discontinuation for renal adverse events suggesting that dose-adjustment may be warranted for long-term safety.

Asymptotic solutions of fractional interval differential equations with nonsingular kernel derivative.

Realizing the behavior of the solution in the asymptotic situations is essential for repetitive applications in the control theory and modeling of the real-world systems. This study discusses a robust and definitive attitude to find the interval approximate asymptotic solutions of fractional differential equations (FDEs) with the Atangana-Baleanu (A-B) derivative. In fact, such critical tasks require to observe precisely the behavior of the noninterval case at first. In this regard, we initially shed light on the noninterval cases and analyze the behavior of the approximate asymptotic solutions, and then, we introduce the A-B derivative for FDEs under interval arithmetic and develop a new and reliable approximation approach for fractional interval differential equations with the interval A-B derivative to get the interval approximate asymptotic solutions. We exploit Laplace transforms to get the asymptotic approximate solution based on the interval asymptotic A-B fractional derivatives under interval arithmetic. The techniques developed here provide essential tools for finding interval approximation asymptotic solutions under interval fractional derivatives with nonsingular Mittag-Leffler kernels. Two cases arising in the real-world systems are modeled under interval notion and given to interpret the behavior of the interval approximate asymptotic solutions under different conditions as well as to validate this new approach. This study highlights the importance of the asymptotic solutions for FDEs regardless of interval or noninterval parameters.

A prospective study of women with ASCUS or LSIL pap smears at baseline and HPV E6/E7 mRNA positive: a 3-year follow-up.

Human papillomavirus (HPV) testing is used in the triage of women with a borderline smear result. The efficiency of testing women with a low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) is less clear. For this reason we used a new HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher specificity. The objective of this prospective study was to assess whether HPV E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to predict those women who have a high risk of developing a histological cervical intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the women's age and HPV DNA genotype and followed them up for 3 years. Cervical samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women were monitored for the development of histopathologically verified CIN2+. Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at the colposcopic examination. Follow-up was available for 312 women, 193 were positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test. Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions and therefore deserve greater attention and earlier check-ups.

Alcohol withdrawal syndrome: mechanisms, manifestations, and management.

The alcohol withdrawal syndrome is a well-known condition occurring after intentional or unintentional abrupt cessation of heavy/constant drinking in patients suffering from alcohol use disorders (AUDs). AUDs are common in neurological departments with patients admitted for coma, epileptic seizures, dementia, polyneuropathy, and gait disturbances. Nonetheless, diagnosis and treatment are often delayed until dramatic symptoms occur. The purpose of this review is to increase the awareness of the early clinical manifestations of AWS and the appropriate identification and management of this important condition in a neurological setting.

An updated Italian normative dataset for the Stroop color word test (SCWT).

The Stroop color and word test (SCWT) is widely used to evaluate attention, information processing speed, selective attention, and cognitive flexibility. Normative values for the Italian population are available only for selected age groups, or for the short version of the test. The aim of this study was to provide updated normal values for the full version, balancing groups across gender, age decades, and education. Two kinds of indexes were derived from the performance of 192 normal subjects, divided by decade (from 20 to 90) and level of education (4 levels: 3-5; 6-8; 9-13; >13 years). They were (i) the correct answers achieved for each table in the first 30 s (word items, WI; color items, CI; color word items, CWI) and (ii) the total time required for reading the three tables (word time, WT; color time, CT; color word time, CWT). For each index, the regression model was evaluated using age, education, and gender as independent variables. The normative data were then computed following the equivalent scores method. In the regression model, age and education significantly influenced the performance in each of the 6 indexes, whereas gender had no significant effect. This study confirms the effect of age and education on the main indexes of the Stroop test and provides updated normative data for an Italian healthy population, well balanced across age, education, and gender. It will be useful to Italian researchers studying attentional functions in health and disease.

Hippocampal sleep spindles preceding neocortical sleep onset in humans.

The coexistence of regionally dissociated brain activity patterns -with some brain areas being active while other already showing sleep signs- may occur throughout all vigilance states including the transition from wakefulness to sleep and may account for both physiological as well as pathological events. These dissociated electrophysiological states are often characterized by multi-domain cognitive and behavioral impairment such as amnesia for events immediately preceding sleep. By performing simultaneous intracerebral electroencephalographic recordings from hippocampal as well as from distributed neocortical sites in neurosurgical patients, we observed that sleep spindles consistently occurred in the hippocampus several minutes before sleep onset. In addition, hippocampal spindle detections consistently preceded neocortical events, with increasing delays along the cortical antero-posterior axis. Our results support the notion that wakefulness and sleep are not mutually exclusive states, but rather part of a continuum resulting from the complex interaction between diffuse neuromodulatory systems and intrinsic properties of the different thalamocortical modules. This interaction may account for the occurrence of dissociated activity across different brain structures characterizing both physiological and pathological conditions.

The impact of loneliness and social isolation on the benefits of an exercise program with hospitalised older adults.

OBJECTIVES: This study aimed to assess the prevalence and impact of loneliness (De Jong Gierveld scale) and isolation (Lubben scale) on the effects of a hospital-based exercise programme. DESIGN: Secondary analysis of a randomised clinical trial. SETTING: Acute Geriatric Unit of a tertiary hospital in Spain. PARTICIPANTS: 103 hospitalised older adults. INTERVENTION: Individualised multicomponent exercise program (20-minute sessions twice a day for 3 consecutive days). RESULTS: Among the 103 randomised patients included in the analysis (both arms included), 58.3% were male, and their mean age was 87.3 (4.5) years. According to the Lubben scale, 15.8% of patients were at risk of isolation, while 62.7% were in a situation of severe or moderate loneliness according to the De Jong Gierveld scale. In the non-isolated group, training showed a substantial positive impact on Geriatric Depression Scale (B = -1.25, 95% CI = -0.24 to -0.27). In the isolated group, all outcomes improved, but only the Quality of Life showed significant changes (B = 35, 95% CI = 4.96-35.8). The SPPB test (B = 1.62, 95% CI = 0.19-3.04) and Quality of Life, (B = 17.1, 95% CI = 1.84-32.3) showed a significant improvement in the non-loneliness exercise group while no differences were found in the loneliness group. CONCLUSION: Despite the high prevalence of loneliness and social isolation, individualised exercise programs provide significant benefits to hospitalised patients, especially in quality of life.

Dual pulsed laser deposition system for the growth of complex materials and heterostructures.

Here, we present an integrated ultra-high-vacuum (UHV) apparatus for the growth of complex materials and heterostructures. The specific growth technique is the Pulsed Laser Deposition (PLD) by means of a dual-laser source based on an excimer KrF ultraviolet and solid-state Nd:YAG infra-red lasers. By taking advantage of the two laser sources-both lasers can be independently used within the deposition chambers-a large number of different materials-ranging from oxides to metals, to selenides, and others-can be successfully grown in the form of thin films and heterostructures. All of the samples can be in situ transferred between the deposition chambers and the analysis chambers by using vessels and holders' manipulators. The apparatus also offers the possibility to transfer samples to remote instrumentation under UHV conditions by means of commercially available UHV-suitcases. The dual-PLD operates for in-house research as well as user facility in combination with the Advanced Photo-electric Effect beamline at the Elettra synchrotron radiation facility in Trieste and allows synchrotron-based photo-emission as well as x-ray absorption experiments on pristine films and heterostructures.

A specific deficit in spatial memory acquisition in post-traumatic stress disorder and the role of sleep in its consolidation.

Posttraumatic stress disorder (PTSD) is characterized by the presence of anatomo-functional hippocampal alterations. To date, the ability to orient within the environment, which relies on hippocampal integrity, has never been investigated in PTSD. We hypothesized that the ability to form a cognitive map of the environment would be impaired in PTSD. Moreover, spatial memory consolidation benefits from postlearning sleep. Because PTSD individuals often complain about sleep disturbances, we hypothesized that any sleep effect on memory performance would be hampered in these subjects. Twenty-two subjects, all survivors of the L'Aquila 2009 earthquake, were divided into a PTSD and a control group, based on clinical evaluation. After an acquisition phase, they were tested twice ("test" and "retest") on a virtual navigation task. In addition, participants were administered the Digit Span and Task Switching. Subjective sleep quality and sleep disturbances were also assessed. The two testing sessions were on consecutive mornings, interspersed with a night of sleep. During the acquisition phase, the PTSD group took more than twice as long to form a cognitive map of the environment compared to the control group. However, once this phase was successfully completed, the two groups did not differ at test, but they tendentially differed at postsleep retest. Additional analyses comparing performances between groups on test-retest difference scores confirm that sleep-dependent consolidation may be differentially affected in the two groups. Our findings are strictly confined to the navigation performance, excluding a generalized cognitive deficit. PTSD also reported more subjective sleep disturbances and shorter sleep time than controls, which were correlated to worse performance at retest. The specific deficit in the formation of a cognitive map reported in PTSD may be related to hippocampal dysfunctions as well as to the sleep disturbances experienced by these patients. The possible deficiency of sleep-dependent spatial performance improvement should however be confirmed by further studies comprising a wake control group.

'My wig has been my journey's companion': perceived effects of an aesthetic care programme for Italian women suffering from chemotherapy-induced alopecia.

This study explored the perceived effects of an aesthetic care/wig programme for Italian women suffering from chemotherapy-induced alopecia. Despite advances in the treatment of many side effects of chemotherapy, alopecia remains difficult to resolve. Literature suggests that patients' reactions to alopecia and camouflaging strategies depend on their gender, individual characteristics, social context, and culture. A qualitative study was designed involving 20 patients from Sicily (Italy), who participated in an aesthetic care programme. Data were collected through semi-structured interviews, and an Interpretative Phenomenological Analysis was conducted on transcriptions. Our findings showed that, even if expected, alopecia is experienced as a traumatic event that challenges a woman's femininity, as reported by many other enquiries. Diverging from other studies, the wig is perceived as very helpful, since it camouflages baldness and reduces the 'sick aspect' related to alopecia. Patients consider their wig to be a 'friend', and it appears that through the aesthetic care programme they received support they otherwise would not have sought. We conclude that aesthetic care/wig programmes can help women affected by alopecia to cope with cancer 'stigma', especially in those rural contexts where psychosocial programmes are not frequently embraced by patients due to environmental and cultural barriers.

Atopic dermatitis (AD) management in an Italian pediatric clinic.

AIM: Atopic dermatitis (AD) is a common, chronic relapsing inflammatory skin disease characterized by dry skin and variable pruritus sometimes associated with allergic disease in other organs as asthma and rhinoconjunctivitis. AD affects deeply the Quality of Life, thus can be extremely disabling and may cause psychological problems for both affected children and their families. METHODS: In order to investigate the estimated prevalence of the disease and the beliefs of the Italian pediatricians, a group of 437 Italian family pediatricians covering a population of almost 380000 children participated in a study based on a questionnaire of 38 items. RESULTS: According to answers of the participants, the incidence of AD has been estimated around 10% of the population and food allergy is believed to be the trigger of the acute phase of the disease in infants. As a second opinion, dermatologists are consulted more frequently than allergologists. CONCLUSION: The use of emollients is advised in general whilst topical corticosteroids treatment is prescribed only in selected cases; more than 50% of pediatricians do not prescribe topical calcineurin inhibitors.

The evolution of the autopsy over the years.

Abstract: Autopsy has played an extremely important role in both the forensic and clinical fields for many years. In recent years, clinical autopsy has become less important, but today, thanks to the pandemic, this importance has been rediscovered. Conversely, forensic autopsy has never lost its importance, but it would need to be updated.