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Objectives: To investigate seasonality, epidemiologic characteristics, and clinical severity variations of respiratory syncytial virus (RSV)-associated hospitalizations following the easing of COVID-19 restrictions in Tuscany, Italy, up to the 2022-2023 season., Methods: From 2017 to 2023, a dynamic cohort consisting of all resident children aged ≤2 years was followed up in regional registries. The person-time incidence rate of RSV-associated hospitalizations per 1,000 person-years and risk of severe hospitalization (intensive care unit, continuous positive airway pressure, or mechanical ventilation) per 100 RSV hospitalizations were calculated. RSV seasonality was investigated with retrospective methods., Results: A total of 193,244 children were followed up. After the easing of restrictions, RSV epidemics showed earlier seasonality and shorter duration compared with pre-pandemic (2017 to 2019), with this deviation decreased in 2022-2023. In 2021-2022 and 2022-2023, the incidence rate of RSV-associated hospitalizations significantly increased compared with pre-pandemic (2022-2023 risk ratio 3.6, 95% confidence interval 3.3-4.0), with larger increases among older age groups. Among hospitalized children, only those aged ≥12 months showed an increased risk of severe hospitalization, particularly during 2021-2022 (risk ratio 4.7, 95% confidence interval 1.5-24.3)., Conclusions: Our findings suggest a gradual return of RSV epidemics to the pre-pandemic pattern, although relevant increases in disease incidence persist. Reduced regular RSV exposure among older children may lead to declining immunity and increased severe outcome risks., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The COVID-19 pandemic significantly changed respiratory viruses' epidemiology due to non-pharmaceutical interventions and possible viral interactions. This study investigates whether the circulation patterns of respiratory viruses have returned to pre-pandemic norms by comparing their peak timing and duration during the first three SARS-CoV-2 seasons to pre-pandemic times., Methods: Global Influenza Surveillance and Response System data from 194 countries (2014-2023) was analyzed for epidemic peak timing and duration, focusing on pre-pandemic and pandemic periods across both hemispheres and the intertropical belt. The analysis was restricted to countries meeting specific data thresholds to ensure robustness., Results: In 2022/2023, the northern hemisphere experienced earlier influenza and respiratory syncytial virus (RSV) peaks by 1.9 months (P <0.001). The duration of influenza epidemics increased by 2.2 weeks (P <0.001), with RSV showing a similar trend. The southern hemisphere's influenza peak shift was not significant (P = 0.437). Intertropical regions presented no substantial change in peak timing but experienced a significant reduction in the duration for human metapneumovirus and adenovirus (7.2 and 6.5 weeks shorter, respectively, P <0.001)., Conclusions: The pandemic altered the typical patterns of influenza and RSV, with earlier peaks in 2022 in temperate areas. These findings highlight the importance of robust surveillance data to inform public health strategies on evolving viral dynamics in the years to come., Competing Interests: Declaration of Competing Interest MH and ImG are employees of CSL Seqirus and may hold shares. JP declares that Nivel has received research grants which concern the epidemiology of influenza and vaccination against influenza from WHO, Sanofi, and the Foundation for Influenza Epidemiology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Respiratory syncytial virus (RSV) is a frequent cause of acute lower respiratory infection in children, imposing a substantial economic burden on healthcare systems. This systematic review aimed to assess the economic burden and healthcare utilisation of RSV in children aged 0-59 months in Italy., Study Design: Systematic review., Methods: A systematic search of PubMed, Embase, Scopus, and the International HTA Database, including studies published in English or Italian, was conducted between January 2000 and July 2022. Inclusion criteria required studies to be conducted in Italy and provide data on the economic costs and healthcare resource utilisation related to RSV infections., Results: Out of 20,845 records screened, 18 articles met the inclusion criteria. Only one study provided comprehensive data on RSV disease costs, including hospitalisation, diagnostic tests, and medical procedures for infants with RSV-bronchiolitis. The mean cost per inpatient was higher for RSV-positive children (€5753.43 ± €2041.62) than that for RSV-negative children. Additionally, five studies reported a median length of hospital stay of 5 days for RSV-infected children, and four studies indicated a higher frequency of intensive care unit admissions for RSV-infected children than for those with other viral infections., Conclusions: This is the first systematic review to examine the economic burden and healthcare utilisation of RSV in children aged 0-59 months in Italy. While limited data were available, the findings underscore the urgency to conduct further research and gather additional evidence on the costs and healthcare resource utilisation associated with RSV infections. Such efforts are essential for informing the development of effective prevention strategies for paediatric RSV infections in Italy., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Prepectoral direct-to-implant reconstruction with acellular dermal matrix (ADM) represents a safe, fast, and successful option in breast reconstruction in a selected cohort of patients. Nowadays, this procedure is considered challenging in thin. Meanwhile, his cohort has not been accurately analyzed yet., Methods: A single institution retrospective cohort study was performed between January 2019 and March 2023 in all women who underwent mastectomy. Biometrical and clinical data were recorded. Also, surgical technique, operating room (OR) time, mastectomy weights, implant choice, and acellular dermal matrix (ADM) types were properly noted. Postoperative complications represented the main topic: these were classified into early and late ones based on onset time. At least 12-month follow-up was required. A comparison between thin and ideal body mass index (BMI) populations was performed., Results: Early complications did not seem to differ between the 2 groups with 37.8% and 38.9% of women having at least 1 early complication in thin and ideal-weight women, respectively (P = .919). In univariable regression analysis, compared with women with a BMI of 22.1 to 25.0, women with a BMI ≤ 22.0 were associated with an increased risk of late complications of 2.84 (1.13-7.14). Specifically, thin women appeared to have a 3-fold increased risk (OR = 2.97, 95% CI 1.08-8.18) of ripples/wrinkles compared with women with ideal weight., Conclusions: Prepectoral reconstruction with ADM in thin patients may be considered as safe as in standard BMI patients. Rippling may be more frequent, but, whenever needed, easy to correct with a few sessions of lipo-grafts., Level of Evidence: III., Competing Interests: Disclosure The authors declare that they have no conflicts of interest to disclose. All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationship, affiliation, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Lung cancer (LC) remains a disease with poor prognosis despite recent advances in treatments. Here, we aimed at summarizing the current scientific evidence on whether quitting smoking at or around diagnosis has a beneficial effect on the survival of LC patients., Methods: We searched MEDLINE and EMBASE for articles published until 31 st October, 2021, that quantified the impact on LC patients' survival of quitting smoking at or around diagnosis or during treatment. Study-specific data were pooled into summary relative risk (SRR) and corresponding 95% confidence intervals (CI) using random effect meta-analysis models., Results: Twenty-one articles published between 1980 and 2021 were included, which encompassed a total of over 10,000 LC patients. There was substantial variability across studies in terms of design, patients' characteristics, treatments received, criteria used to define smoking status (quitters or continued), and duration of follow-up. Quitting smoking at or around diagnosis was significantly associated with improved overall survival (SRR 0.71, 95% CI 0.64-0.80), consistently among patients with non-small cell LC (SRR 0.77, 95% CI 0.66-0.90, n studies = 8), small cell LC (SRR 0.75, 95% CI 0.57-0.99, n studies = 4), or LC of both or unspecified histological type (SRR 0.81, 95% CI 0.68-0.96, n studies = 6)., Conclusions: Quitting smoking at or around diagnosis is associated with a beneficial effect on the survival of LC patients. Treating physicians should educate LC patients about the benefits of quitting smoking even after diagnosis and provide them with the necessary smoking cessation support., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the extent to which food items are a source of extended-spectrum β-lactamase (ESBL) -producing Escherichia coli (ESBL-Ec) and ESBL-producing Klebsiella pneumoniae (ESBL-Kp) for humans in five European cities., Methods: We sampled 122 human polluted (hp)-environments (sewers and polluted rivers, as a proxy of human contamination) and 714 food items in Besançon (France), Geneva (Switzerland), Sevilla (Spain), Tübingen (Germany) and Utrecht (The Netherlands). A total of 254 ESBL-Ec and 39 ESBL-Kp isolates were cultured. All genomes were fully sequenced to compare their sequence types (ST) and core genomes, along with the distribution of bla ESBL genes and their genetic supports (i.e. chromosome or plasmid)., Results: Sequence data revealed that ESBL-Ec and ESBL-Kp isolates from hp-environments were genetically different from those contaminating food items. ESBL-Ec ST131 was widespread in the hp-environment (21.5% of the isolates) but absent from the food items tested. ESBL-Ec ST10 was in similar proportions in hp-environments and food items (15 and 10 isolates, respectively) but mostly carried reservoir-specific bla ESBL . bla CTX-M-1 and bla SHV-12 predominated in food-related E. coli isolates (32% and 34% of the isolates, respectively), whereas bla CTX-M-15 and bla CTX-M-27 predominated in isolates from hp-environments (52% and 15% of the isolates, respectively)., Conclusions: We found a very limited connection between ESBL-Ec and ESBL-Kp populations retrieved in food items and from hp-environments and bla ESBL . This suggests that human-to-human contamination, rather than the food chain, is possibly the most frequent route of ESBL-Ec and ESBL-Kp transmission in high-income countries., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Safety of reconstructive microsurgery in elderly patients is still a topic of debate, because no conclusive evidence exists that provides indications and risk evaluation in elderly patients. The purpose of this study, which the Italian Society for Plastic, Reconstructive, and Aesthetic Surgery (SICPRE) has promoted, is to evaluate the safety and the complication risk of elective reconstructive microsurgery in elderly patients as well as to identify patient- or procedure-related risk factors. The secondary aim is to evaluate the predictive role for complications of the Geriatric 8 score (G8)., Methods: A total of 194 consecutive patients from 18 centers, aged 65 or older, who received an elective microsurgical flap between April 2018 and April 2019 were prospectively evaluated. Patient-related, treatment-related, and outcomes data were recorded and statistically analyzed through multiple-adjusted logistic regression models., Results: Our study showed an increased risk of complications and a longer hospitalization in patients aged ≥75 years with the American Society of Anesthesiologists (ASA) score ≥3 (or G8 score ≤11) as compared to patients >65 years of age and <75 years of age who undergo reconstruction with a microsurgical flap. Instead, flap survival did not significantly vary with age, but was associated only with ASA score ≥3 (or G8 score ≤11) and surgeries that last longer than 480 min; however, flap survival (92.3%) was slightly lower than that commonly reported for in the general population., Conclusions: Reconstructive microsurgery in the elderly is generally safe. The ASA score is easier and quicker than the G8 score and equally useful for risk stratification., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: The appearance of a symptomatic neuroma following finger amputation is a devastating consequence for patient's quality of life. It could be cause of chronic neuropathic pain. The prevention of neuroma formation is a challenging effort for hand surgeons. The biological mechanisms leading to neuroma formation are mostly unknown and different preventing procedures have been tried without certain results. In this paper, a panel of Italian hand surgeons have been asked to express appropriateness about potentially preventive techniques of neuroma formation following the RAND/UCLA appropriateness protocol., Methods: A literature review was preliminarily performed identifying the most employed methods to reduce the pathologic nerve scar. Afterwards, the selected panelists were asked to score the appropriateness of each procedure in a double scenario: in case of a sharp amputation or in a tear injury. The appropriateness was evaluated according to RAND/UCLA protocol., Results: Nine Italian hand surgeons were included in the panel. Of them 5 were orthopaedic surgeons, 4 plastic surgeons. The identified appropriate procedures were: revision amputation should be done in operating room, the neurovascular bundles should be identified and is mandatory to treat surrounding soft tissues. Only in case of clean-cut amputation, it is appropriate to perform a proximal extension of the dissection, to use diathermocoagulation and coverage with local flaps. Procedures such as shortening in tension of the nerve stump, bone shortening, implantation of the nerve end in the soft tissue, treatment in the emergency room and, in both scenarios, certain results are evaluated as uncertain., Discussion: In order to prevent the formation of a distal stump neuroma few methods were judged appropriate. It is mandatory to identify the neurovascular bundles and treat also the surrounding tissues, but no certain results could be obtained with local flap, bone shortening and other ancillary surgical acts. Moreover, it is not possible to guarantee the non arising of neuroma in any cases, also when every procedure has been temped., Conlusions: The prevention of distal neuroma is actually a challenge, without a well known strategy due to the variability of response of nervous tissue to injury., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

COVID-19 represents a major public health issue in Italy; estimating the size of the outbreak could direct public health policies and inform us of the extent of the reorganization needed in the healthcare system, the efficacy of quarantine measures, and eventually on the achievement of herd immunity. To chart the real extent of COVID-19 infection in Italy official data need to be interpreted, considering various aspects such as the "suspected-case" definition that changed during recent months, the management of asymptomatic and untested symptomatic cases, the system for reporting deaths, and short-term fluctuations. All these aspects should be considered when reflecting on the meaning of the official COVID-19 figures in Italy. Regionalization of the healthcare system and fragmentation of data represent real challenges in the management of the COVID-19 outbreak in Italy. The authors' opinion is that transparent and accurate reporting could guide policy-making and help reorganize health services., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Defects of the Achilles tendon region represent a challenge for reconstructive surgeons. Several options are available but there is still no reconstructive ladder for this specific and tricky area. An up-to-date reconstructive ladder according to local and general conditions is proposed based on our multicentre experience and an extensive review of the English literature on PubMed., Materials and Methods: An extensive review of the English literature was performed on PubMed using the following key-words: "Achilles region", "heel", "soft-tissue reconstruction", "flaps", "grafts" and "dermal substitutes"., Results: A total of 69 complete papers were selected, covering the last thirty years' literature. Although most of the studies were based on limited case-series, local and general conditions were always reported. A comprehensive reconstructive ladder of all the available reconstructive techniques for the Achilles region has been created based on our personal multicentre experience and the results of the literature review., Conclusions: The reconstructive ladder is a concept that is still a mainstay in plastic surgery and guides decisions in the repair strategy for soft tissue defects. The optimal solution, according to the experience of the surgeon and the wishes of the patient, is the one that implies less sacrifice of the donor site. Perforator flaps should be the first-line option for small-to-moderate defects; the distally-based sural flap is the most reported for moderate-to-large defects of the Achilles region, and free flaps should be reserved mainly for complex and wide reconstructions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background & Aims: Human biliary tree stem/progenitor cells (hBTSCs) are multipotent epithelial stem cells, easily obtained from the biliary tree, with the potential for regenerative medicine in liver, biliary tree, and pancreas diseases. Recent reports indicate that human mesenchymal stem cells are able to modulate the T cell immune response. However, no information exists on the capabilities of hBTSCs to control the allogeneic response. The aims of this study were to evaluate FasL expression in hBTSCs, to study the in vitro interaction between hBTSCs and human lymphocytes, and the role of Fas/FasL modulation in inducing T cell apoptosis in hBTSCs/T cell co-cultures., Methods: Fas and FasL expression were evaluated in situ and in vitro by immunofluorescence and western blotting. Co-cultures of hBTSCs with human leukocytes were used to analyze the influence of hBTSCs on lymphocytes activation and apoptosis., Results: hBTSCs expressed HLA antigens and FasL in situ and in vitro. Western blot data demonstrated that hBTSCs constitutively expressed high levels of FasL that increased after co-culture with T cells. Confocal microscopy demonstrated that FasL expression was restricted to EpCAM(+)/LGR5(+) cells. FACS analysis of T cells co-cultured with hBTSCs indicated that hBTSCs were able to induce apoptosis in activated CD4(+) and CD8(+) T cell populations. Moreover, the Fas receptor appears to be more expressed in T cells co-cultured with hBTSCs than in resting T cells., Conclusions: Our data suggest that hBTSCs could modulate the T cell response through the production of FasL, which influences the lymphocyte Fas/FasL pathway by inducing "premature" apoptosis in CD4(+) and CD8(+) T cells., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate the ability of human amniotic fluid stem cells and human dental pulp stem cells to differentiate into insulin-producing cells., Methods: Human amniotic fluid stem cells and human dental pulp stem cells were induced to differentiate into pancreatic β-cells by a multistep protocol. Islet-like structures were assessed in differentiated human amniotic fluid stem cells and human dental pulp stem cells after 21 days of culture by dithizone staining. Pancreatic and duodenal homebox-1, insulin and Glut-2 expression were detected by immunofluorescence and confocal microscopy. Insulin secreted from differentiated cells was tested with SELDI-TOF MS and by enzyme-linked immunosorbent assay., Results: Human amniotic fluid stem cells and human dental pulp stem cells, after 7 days of differentiation started to form islet-like structures that became evident after 14 days of induction. SELDI-TOF MS analysis, revealed the presence of insulin in the media of differentiated cells at day 14, further confirmed by enzyme-linked immunosorbent assay after 7, 14 and 21 days. Both stem cell types expressed, after differentiation, pancreatic and duodenal homebox-1, insulin and Glut-2 and were positively stained by dithizone. Either the cytosol to nucleus translocation of pancreatic and duodenal homebox-1, either the expression of insulin, are regulated by glucose concentration changes. Day 21 islet-like structures derived from both human amniotic fluid stem cells and human dental pulp stem cell release insulin in a glucose-dependent manner., Conclusion: The present study demonstrates the ability of human amniotic fluid stem cells and human dental pulp stem cell to differentiate into insulin-producing cells, offering a non-pancreatic, low-invasive source of cells for islet regeneration., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

MATER (Maternal Antigen That Embryos Require) is an oocyte-specific protein dependent on the maternal genome and required for early embryonic development. The gene products expressed in oocytes play important roles in folliculogenesis, fertilization and pre-implantation development. The aim of this study was to characterize the localization and distribution pattern of the human MATER protein during follicular development and after ovulation, to determine its functional role. Immunocytochemistry experiments coupled with confocal and electron microscopy analysis were carried out to determine the ultrastructural localization of MATER in human ovarian tissue and in isolated oocytes, obtained during IVF procedures. Human cumulus cells were cultured, with or without cycloheximide, to confirm endogenous biosynthesis of the protein. Human MATER is detectable at the onset of the follicular maturation process, suggesting this protein has a role at earlier stages in the human compared with other mammalian species. The presence of MATER is specific to the oocyte and follicular cells that, during maturation, are spatially and functionally associated with the oocyte. The nuclear, nucleolar and mitochondrial localization hints at a possible role in RNA processing and the metabolic activity of the cell.

Multidrug-resistant isolates of a clonal lineage of Pseudomonas aeruginosa producing the VIM-2 metallo-beta-lactamase (MBL), involved in a large outbreak in an Italian hospital, were compared with MBL-negative strains that had caused outbreaks in two French hospitals. Although the isolates had different carbapenem MICs, the VIM-2-producing isolates from Italy carried identical, or very similar, allelic forms of the oprD gene, harboured a common class 1 integron, belonged to the same multilocus sequence type (ST111), and showed macrorestriction profiles that were related to those of the MBL-negative French strains. These results support the concept of independent acquisition of resistance determinants by members of a widespread clonal lineage of P. aeruginosa.

Emerin is an ubiquitous protein localized at the nuclear membrane of most cell types including muscle cells. The protein is absent in most patients affected by the X-linked form of Emery-Dreifuss muscular dystrophy, a disease characterized by slowly progressive muscle wasting and weakness, early contractures of the elbows, Achilles tendons, and post-cervical muscles, and cardiomyopathy. Besides the nuclear localization, emerin cytoplasmic distribution has been suggested in several cell types. We studied the expression and the subcellular distribution of emerin in mouse cultured C2C12 myoblasts and in primary cultures of human myoblasts induced to differentiate or spontaneously differentiating in the culture medium. In differentiating myoblasts transiently transfected with a cDNA encoding the complete emerin sequence, the protein localized at the nuclear rim of all transfected cells and also in the cytoplasm of some myoblasts and myotubes. Cytoplasmic emerin was also observed in detergent-treated myotubes, as determined by electron microscopy observation. Both immunofluorescence and biochemical analysis showed, that upon differentiation of C2C12 cells, emerin expression was decreased in the resting myoblasts but the protein was highly represented in the developing myotubes at the early stage of cell fusion. Labeling with specific markers of myogenesis such as troponin-T and myogenin permitted the correlation of increased emerin expression with the onset of muscle differentiation. These data suggest a role for emerin during proliferation of activated satellite cells and at the early stages of differentiation.

Knock-out of the gene coding for caveolin-1, the main organizer of caveolae, has not yet been performed. We devised a strategy to knock-down caveolin-1 gene expression using antisense oligodeoxynucleotides (ODNs). Seven ODNs, covering different regions of caveolin-1 mRNA, were screened by Western blot analysis of caveolin-1 levels. The most active and specific was found to reduce caveolin-1 protein levels by 70% at 1 microM concentration and its action, as demonstrated by a marked reduction (about 50%) in caveolin-1 mRNA levels, was due to a true antisense mechanism. In HUVEC treated with the active ODN, caveolae were undetectable by confocal and electron microscopy, while their number was not affected when cells were treated with a scrambled ODN. Using the fibrin gel 3 D angiogenesis test we established that the active (but not the scrambled) ODN strongly suppressed capillary-like tube formation. Moreover, an antisense tailored against chicken caveolin-1 mRNA, when tested using the chorio-allantoic membrane technique, dramatically reduced vessel formation at doses (10-20 microg) under which control ODNs were ineffective and devoid of toxicity. Thus, it is likely that caveolin-1 down regulation, followed by caveolae disruption, impairs angiogenesis in vitro and in vivo., (Copyright 2000 Academic Press.)

We have investigated the role of sensory nerves in regulating airway smooth muscle function in the guinea-pig, marmoset, rabbit and man. Tissue levels of the sensory neuropeptides CGRP and substance P in the airways of the guinea-pig were significantly greater compared with the rabbit and marmoset. The relative order of tissue content was guinea-pig >>> rabbit = marmoset. Marmoset bronchial and tracheal preparations responded weakly to exogenously administered substance P and neurokinin A but contracted to methacholine and demonstrated atropine-sensitive cholinergic responses. In marmoset, rabbit and human airway preparations, capsaicin mediated weak contractile responses to exogenously administered capsaicin. However, high concentrations of capsaicin elicited a relaxation response that was epithelium-independent, cyclo-oxygenase-insensitive, not involving nitric oxide and not dependent on the activation of capsaicin-sensitive afferents. These results suggest that rabbit and marmoset airways respond functionally in a similar way to human airway preparations and maybe more relevant than guinea-pig airways with regard to understanding the role of sensory neuropeptides in airways.

In three groups of rabbits, the rectus femoris muscle was subjected to 4 hours of total ischaemia. In Group 1 (normothermia, n = 5) the core temperature was maintained within the range 36-38 degrees C for the duration of ischaemia. In Group 2 (total hypothermia, n = 5) the core temperature was allowed to fall to 31.5-33.5 degrees C. In Group 3 (muscle only hypothermia, n = 5) core temperature was maintained as in Group 1 but the muscle temperature was allowed to fall to 29.5-31.5 degrees C. After 24 hours of reperfusion the muscles were harvested and measurements made of muscle viability, oedema and myeloperoxidase content. The mean (s.e.m.) muscle viability of Group 1, 19.5 (3.8)%, was significantly less than that of both Group 2, 86.0 (2.0)%, and Group 3, 87 (4.1)%, (P < 0.001). Muscle oedema and myeloperoxidase levels were elevated in all experimental groups, but differences were not significant. These findings indicate that ischaemia-reperfusion injury in skeletal muscle in this model is highly temperature-sensitive, small reductions in muscle temperature during ischaemia providing significant protection against ischaemia-reperfusion injury.

HIV-1 infection may be complicated by a number of psychopathological conditions. While organic mental disorders, such as HIV-related psychosis and dementia, are late manifestations, mood disorders may occur during both asymptomatic and symptomatic stages of infection. The possible impact of brain involvement due to neurotropism of HIV-1 has not been investigated systematically in these latter conditions. The psychiatric caseness of HIV-seropositive individuals without AIDS and seronegative controls was assessed using a standardized clinical interview (Present State Examination). A comparison was made between individuals with and without psychiatric caseness using clinical, neuropsychological, and neurophysiological assessments. An increased prevalence of current psychiatric illness was found in subjects with early symptomatic HIV infection compared to those with asymptomatic infection and controls. This could not be attributed to psychiatric history, as well as to clinical and immunological markers of HIV infection, however, psychiatric caseness in early symptomatic infection was associated with marked neurophysiological changes, detectable by quantitative electroencephalography. Altogether, this study provided preliminary evidence that psychiatric symptoms in symptomatic but not asymptomatic HIV infection may be associated with subtle brain involvement preceding the immunological and neurocognitive impairment characteristic for AIDS.

Prospective relations between individual differences in both lateralised neuro-psychophysiological functions and mood ratings with immune status (CD4 and CD8 counts) were examined in asymptomatic HIV-positive men (n = 27) over thirty months. They participated in a controlled study of zidovudine versus placebo (results published elsewhere). Measures included EEG spectra, neuropsychological tests and mood ratings. A model of reciprocal lateralised influences on the immune system was tested whereby patients with left superior to right hemispheric functions were predicted to show a less deleterious outcome than those with the opposite asymmetry pattern. Prospective relations with immune status were found in the EEG with lateralised theta, alpha and beta activity; among cognitive measures with word fluency, semantic processing, and lateralised motor and recognition memory (word/face) processes; with mood ratings including depression, confusion and the total mood score. The nature of the effects supported the laterality predictions. These unique data, showing that neuro-psychophysiological factors in HIV+ but otherwise healthy subjects predict immune competence and compromise present 2-3 years later, warrant replication in a larger cohort.

Six patients underwent re-exploration of the carpal tunnel for symptoms of recurrent median nerve compression. All patients had previously undergone two or more decompressions. Operative findings revealed evidence of chronic scarring of the median nerve with flattening and perineural fibrosis. Following decompression together with neurolysis and tenosynovectomy, a vascularized fascial flap pedicled distally on the radial artery was used to envelop the median nerve. Follow-up studies of between 12 and 61 months (mean, 25 months) showed improvement of symptoms in all patients, with 2 patients describing complete relief of pain and paresthesia and 4 patients describing mild intermittent pain or paresthesia.

A modification of the temporalis muscle transfer for facial animation in facial palsy is described. Seven cases are presented which demonstrate the advantages of the procedure, especially the avoidance of temporal hollowing and the greater power due to less dissection of the muscle belly, a more direct line of pull and the absence of a pulley. In addition, food pooling in the buccal sulcus is reduced, and the procedure is less extensive and thus better tolerated.

The effect of early antiretroviral medication with zidovudine on neurophysiological functions was evaluated in subjects with asymptomatic HIV-1 infection. Patients were recruited participants of a larger double-blind randomised placebo-controlled treatment trial with zidovudine (Concorde). The main outcome measures included: quantitative electroencephalography (QEEG), auditory event-related potentials (AEP) and pattern-reversal visual evoked potentials (PRVEP), as well as standard clinical, virological and immunological markers. No significant impairment and no difference between treatment groups was found in visual P100 latency and auditory long-latency P3 responses which is in agreement with the absence of neurological and neuropsychological impairment over the study period. Significant treatment effects were revealed by quantitative electroencephalography (QEEG). While the placebo group showed a significant increase in delta and theta slow frequency QEEG activity over the study period, slow wave amplitude remained unchanged in the zidovudine group after a mean follow-up period of 28 months. In summary, the data provide evidence for a low level neuropathological process in asymptomatic HIV-1 infection which can be effectively suppressed by antiretroviral medication.

The present study investigates the development and maintenance of airway hyperresponsiveness in neonatally immunized rabbits. Rabbits were immunized within 24 hr of birth with the antigen Alternaria tenuis together with aluminum hydroxide as an adjuvant, followed by repeated antigen and adjuvant administration up to 3 months of age. Anesthetized, spontaneously breathing rabbits immunized according to this protocol exhibited a 3.7- (p < 0.01) and 1.8-fold (p < 0.05) increase in airway responsiveness to inhaled histamine when compared with groups of naive or sham-immunized rabbits, respectively. In the absence of further antigen challenge, these changes in airway responsiveness to histamine in a subpopulation of antigen-immunized rabbits persisted for up to 12 months of age. This hyperresponsiveness was not associated with an alteration in either total or differential inflammatory cell numbers as assessed by bronchoalveolar lavage (BAL), and no significant differences in isolated bronchial smooth muscle responsiveness to methacholine, histamine, theophylline, or electrical field stimulation were observed. These results demonstrate that neonatal immunization of rabbits with Alternaria tenuis can lead to the development of persistent airway hyperresponsiveness, and that the maintenance of this state is unrelated to either a detectable alteration in cellular infiltration within the airway lumen or changes in bronchial smooth muscle responsiveness. It is suggested that neonatal exposure to antigen and adjuvant may be important determinants for the development of persistent airway hyperresponsiveness. This animal model may provide a useful way to investigate the effects of drugs on airway hyperresponsiveness.

Motor dysfunctions are amongst the earliest and most common signs of brain impairment caused by human immunodeficiency virus (HIV) infection. Topographical EEG was recorded in patients both with asymptomatic and early symptomatic infection (without acquired immunodeficiency syndrome (AIDS) defining illness), as well as in seronegative controls under resting and motor activation conditions. While patients' motor performance did not differ from control values, the EEG showed a consistent increase in rhythmic activity in Theta, Alpha and Beta frequency bands in Symptomatics. This amplitude increase was evident in different topographical regions during resting states as compared with motor activation, findings which suggest concurrent involvement of several motor areas possibly due to a functional impairment in subcortical integratory mechanisms. Comparing motor task and baseline both patient groups showed less consistent patterns of task-related EEG amplitude reduction than found in the control group. Here topographical EEG in connection with motor activation procedures was found to be more sensitive than behavioral measures of motor performance and offers a technique to assess treatment effects before the development of motor abnormalities in patients with HIV infection.

Auditory and visual event-related brain potentials (ERPs) were used to complement neuropsychological and medical assessment in neurologically healthy subjects with asymptomatic and symptomatic human immunodeficiency virus type 1 (HIV-1) infection. Auditory and visual ERPs, recorded using standard oddball paradigms, disclosed delays in late waves (N2 and P3) in symptomatic subjects (CDC stage IV) when compared with matched controls. Abnormally delayed P3 waves in at least one modality were recorded in 41% of symptomatics and this was associated with deficits in neuropsychological performance, particularly psychomotor slowing. However, no differences in late wave latencies between asymptomatic and control subjects were found, though asymptomatics showed delays in auditory N1 and P2 latencies. The number of morphological abnormalities, such as indiscernible late waves as well as topographical variability of the P3 wave, was increased in both HIV seropositive groups and possibly indicates a distinct mechanism of impairment, different from latency delay. Whilst P3 delay in symptomatics was not associated with changes in immune function (T4 cells) there was, however, a link with anaemia and subclinical hepatic dysfunction.

The photomutagenicity of the furochromone khellin was tested in Ames Salmonella strains using 8-methoxypsoralen (8-MOP) and 4,5', 8-trimethylpsoralen (TMP) as positive controls. When khellin was assayed with strain TA1537, mutation induction was not detectable; in the same strain, an equitoxic dose (52-56% level of survival) of TMP (used at a concentration 12-fold lower than khellin and with a UVA dose 83-fold lower than that used with khellin) yielded an increase in revertants/plate 3-fold above the spontaneous background. In strain TA102, khellin plus UVA treatment yielded a 2-fold increase in revertants/plate above the spontaneous background (79% survival). 8-MOP, however, used at a concentration 8-fold lower than khellin with a UVA dose 13-fold lower than khellin, yielded an increase in revertants/plate about 14-fold above background (66% survival) in the same strain. These data show that khellin has a weak photomutagenic potential and, along with the previously reported low photogenotoxic potential in eukaryotic cell systems, support the notion that khellin may be safer than bifunctional psoralens for clinical use.

Many current techniques for vulval reconstruction following cancer excision satisfy the basic requirements for restoration of urinary and sexual function but leave considerable scars on the thigh. We suggest the use of bilateral island groin flaps, which allow a good cosmetic and functional reconstruction with a minimal donor defect and more acceptable scars. This technique also allows good access to the inguinal, crural and iliac lymph nodes through the same incisions, avoiding other scars.