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Gigantomastia, characterized by excessive breast size (usually heavier than 2.5 kg), can result from various causes and significantly affect patients' lives. Surgical intervention is often required, and over time, several techniques have been developed for its treatment. These techniques aim to address the functional and aesthetic concerns associated with gigantomastia, providing relief to patients and improving their quality of life. A 40-year-old primiparous housewife developed unilateral gigantomastia as a consequence of hormone therapy. To address this, a modified reduction mammoplasty procedure was undertaken, incorporating NAC (Nipple-Areola Complex) grafting. The reduction involved removing 3450 g of tissue, resulting in restored breast symmetry and enabling the patient to reintegrate into normal daily life. Compared to the traditional technique, the introduction of some modifications in the design allowed for the absence of complications such as dehiscence of the scar at the intersection of the T, the failure of the nipple graft attachment, and the maintenance of a conical shape over time, enabling complete symmetrization of the two breasts. The use of a modified version of the Thorek technique allowed for optimal functional and aesthetic restoration even in the case of a significantly disproportionate breast compared to the contralateral one, with no complications. • Gigantomastia is a debilitating condition with multiple potential causes. • It can manifest as either bilateral or unilateral, leading to noticeable asymmetry between the two breasts. • Various approaches can be employed for its treatment, distinguished by the use of pedicled nipple flap or nipple grafting. • In this work we present our experience with a modified Nipple-Areola Complex grafting technique. [ABSTRACT FROM AUTHOR]

[Display omitted] • The composition of Golden Tomato (GT) juice was characterized in terms of phytonutrients. • GT juice modulates brain impairment induced by Metabolic Syndrome (MetS). • GT juice restores anxiety-like behaviour, reactivity and declarative memory in MetS. • GT juice reduces MAPK-ERK and re-establishes PI3K/Akt signalling in specific brain areas. "Golden" tomato (GT) plays a protective role in metabolic dysfunction induced by High-Fat Diet (HFD). Our aim is to characterize the phytonutrient composition of the juice and explore the influence of GT, orally administered for one month, on cognitive impairment associated with Metabolic Syndrome (MetS) in male rats. We investigated reactivity, stress response and memory, together with brain neurotrophic/inflammatory signaling. Our data showed that HFD-induced functional modifications were ameliorated by GT nutritional supplementation. In particular, the behavioural reactivity improved in HFD/GT rats, that also showed a better performance in tests measuring anxiety and anhedonia. Furthermore, GT consumption rescued the declarative memory impairment. Lastly, GT supplementation counteracted HFD-induced brain alterations in PI3K\Akt and MAPK/ERK signalling pathways. In conclusion, this study provides evidence of the importance of food supplementation with GT in the protection from neuroinflammation and cognitive alterations associated with MetS. [ABSTRACT FROM AUTHOR]

Highlights • Skin Cancer. • Colorectal Cancer. • Cutaneous Metastases. • Fasciocutaneous Flaps. Abstract Introduction Metastases represent one of the most outstanding characteristics of malignant neoplasms and are relatively rare in the skin, in spite of the great extension of the cutaneous organs. Development of cutaneous metastases from colon cancer is a rare event, usually occurring in widely disseminated disease and commonly leading to a poor prognosis. As to location, cutaneous metastases often favor areas close to the primary malignancy, such as lung cancer and skin metastases on the trunk. However, remote sites as the scalp may be also involved. Case presentation We present the case of a 92-year-old female patient with a massive single nodular skin lesion on her left supraclavicular area, that came back positive for cutaneous metastasis of colon adenocarcinoma. Discussion Cutaneous metastasis of colorectal cancer a rare event (2.3%–6%) that usually occur two years after the detection or resection of the primary tumor. It seldom occurs before the identification of the primary tumor and involvement of secondary organs, such as the liver. There are few cases reported with only cutaneous metastases. Conclusion In conclusion, dermatological evaluation of patients who are undergoing screening or who have already been diagnosed with cancer is extremely important. [ABSTRACT FROM AUTHOR]

Introduction Hemipelvectomy with immediate reconstruction with prosthetic devices for the surgical treatment of malignant tumors is an invasive procedure with many possible complications such as wound breakdown, seroma, hematoma and infection. The treatment of an exposed hip implant in these cluster of patient is extremely challenging and the literature shows how negative pressure wound therapy and myocutaneous, both pedicled and free, flaps are workhorses in these situations. Case report In this paper we report a successful coverage of exposed prosthetic hip implant with a local fasciocutaneous flap in a patient in which any other kind of reconstruction was not feasible. Discussion Fasciocutaneous flaps can be considered as an easily performed and minimally invasive surgical procedure, particularly reliable even in patients in poor general conditions, with preservation of future flap options. [ABSTRACT FROM AUTHOR]

Introduction According to literature, primary Hodgkin’s lymphomas of the breast represent one of the rarer entity in the primary breast lymphoma (PBL) scenario. This is the reason why these tumors are insidious in mammary oncology. Presentation of the case We report a case of HL primitive breast in an elderly patient in whom radiology suspected an advanced breast cancer with ipsilateral axillary involvement and in which the fine-needle aspiration came back not significant. Discussion Eighteen cases of primary Hodgkin’s lymphoma of the breast has been described in Literature in a very large period of time: from 1928 to 2016. The nodular sclerosis type is the most frequent histological variant. Conclusion Their rarity together with the fact that radiological investigations are not significant for the purpose of an exact diagnosis, make these lesions extremely difficult to identify. [ABSTRACT FROM AUTHOR]

Introduction Lipomas are the most common benign tumors of the adipose tissue and can be located in any region of the body. In most cases lipomas are small and asymptomatic, but they can at times reach considerable dimensions and, depending on their anatomic site, hinder movements, get inflamed, cause lymphedema, pain and/or a compression syndrome. Presentation of case We here report the case of an otherwise healthy patient who came to our observation with a giant bulk in the left lumbar region which had been showing progressive growth in the previous 5–6 years. Physical examination, ultrasound and MRI were carried out in order to characterize the size, vascularization and limits of the lesion. Due to the pain and restriction of movement that this bulky lesion caused, surgical excision of the lesion was performed. Discussion Giant lipomas display an important differential diagnosis problem with malignant neoplasms, especially liposarcomas, with which they share many features; often the final diagnosis rests on histological evaluation. We here discuss the diagnostic problems that arise with a giant lipoma and all the possible approaches concerning treatment of such a big lesion, explaining the reasons of our approach and management of a common tumor in our case presenting unusual dimensions and location. Conclusion Our approach revealed to be successful in order to nurse our patient's pain, restore the mobility and address the aesthetic issues that this lesion caused. Postoperative checkups were carried out for one year and no signs of relapse have been reported. [ABSTRACT FROM AUTHOR]

INTRODUCTION Gynecomastia is the benign proliferation of the glandular tissue in the male breast. This condition is thought to be caused by the imbalance between estrogen action relative to androgen action at the breast tissue level. Bilateral gynecomastia is frequently found in the neonatal period, early in puberty, and with increasing age. Prepubertal unilateral gynecomastia in the absence of endocrine abnormalities is extremely rare, with only a few cases in literature. PRESENTATION OF CASE We present an otherwise healthy boy of 12 years old with unilateral breast masses. No abnormalities were found on ultrasonography and on all endocrine parameters. Treatment consisted in a new “modified” Webster technique. DISCUSSION The results confirmed validity of this technique in terms of esthetic and functional results, and patient satisfaction. Atypical presentations of gynecomastia are often not recognized. The main pathophysiology of gynecomastia is alteration in the balance between the stimulatory effect of estrogen and the inhibitory effects of androgens on the development of the breast. If there is no causal treatment, surgical resection is the therapy of first choice. CONCLUSION The exact mechanism of unilateral gynecomastia formation in our case is unclear. The evaluation of unilateral gynecomastia can therefore be complex. In conclusion, the surgical treatment of unilateral gynecomastia requires an individual approach, based on an appropriate diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Highlights: [•] Different doses of DMSO are tested in 3 groups of rats after 5 stable epileptic discharges in the DG. [•] 100% and 50% solutions of DMSO with a dose dependent effect reduce the epileptic activity. [•] We infer that DMSO dampens excitotoxic phenomena reducing the glutamatergic transmission. [ABSTRACT FROM AUTHOR]

Abstract: The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB1 receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB1 antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation – MDA) in the rat. WIN55,212-2 (21mgkg−1) exerted an anticonvulsant effect, significantly reduced by the pre-treatment with AM251 (1mgkg−1, 30min interval). Surprisingly, AM251, administered alone at the same dose, failed to induce any modification in MDA responses. Our data suggest the involvement of the CB system in the inhibitory control of hyperexcitability phenomena in a model of acute partial epilepsy. Although the MDA model per se does not induce a basal activation of CB1 receptors, as suggested by the lack of efficacy of AM251 when administered alone, the partial suppression of WIN55,212-2-induced effects in rats pre-treated with AM251 allows to hypothesise that the WIN55,212-2-induced antiepileptic effect is strictly linked to an increased CB1 receptor activation or to the involvement of further receptor subtypes. [Copyright &y& Elsevier]

Abstract: The effects induced on the discharge of subthalamic spontaneously active neurons by inhibiting the enzyme nitric oxide synthase was studied in two groups of urethane-anesthetized rats. In the first group of animals (n =10), the activity of subthalamic single units was recorded before and after the systemic administration of 7-nitro-indazole (7-NI, 50mg/kg i.p.), a selective inhibitor of neuronal nitric oxide synthase. In the second group of rats (n =15), Nω-nitro-l-arginine methyl ester (L-NAME), another inhibitor of nitric oxide synthase, was iontophoretically administered while performing single unit extracellular recordings. The activity of most tested spontaneously discharging neurons (8/10) was influenced by 7-NI administration, which always caused a statistically significant decrease in the firing rate of the responsive cells. In contrast, the iontophoretic administration of L-NAME, although influencing many cells (24/32), did not have univocal effects: in fact, 18 cells were inhibited while 6 neurons were excited in a statistically significant manner. We hypothesize that nitric oxide neurotransmission could exert a tonic modulatory influence upon spontaneously discharging subthalamic neurons, with a prevalent excitatory effect. [Copyright &y& Elsevier]

We have chosen to study the effects of both nitric oxide (NO) and cholecystokinin neuromodulatory systems in some motor structures that are frequently involved in excitotoxic phenomena. In particular, 7-nitroindazole, a selective inhibitor of neuronal NO synthase, was administered in control and sulfated cholecystokinin octapeptide-treated rats. Cortical surface, striatal and pallidal depth bioelectric activities were examined through Fast Fourier Transform analysis. Cortical and pallidal recordings revealed an increase of rapid standard rhythms after the inhibition of neuronal NO synthase; in contrast, striatal depth recordings showed a marked increase of slow standard rhythms. All these effects were completely abolished by chronic pre-treatment with sulfated cholecystokinin octapeptide. The results suggest a functional co-operation between cholecystokinin and NO systems in the modulation of the bioelectric activity of all the motor structures examined, and the possibility of preventing excitotoxic damages induced by an anomalous balance between excitatory and inhibitory neurotransmitters in these areas. [Copyright &y& Elsevier]

Single units were recorded in the striatum and in the globus pallidus (GP) of urethane-anesthetized rats under microiontophoretic administration of either Nω-nitro-l-arginine methyl ester (l-NAME, inhibitor of nitric oxide synthase), or 3-morpholino-sydnonimin-hydrocloride (SIN-1, nitric oxide, NO donor). A steady baseline firing of sporadically discharging striatal neurons (basal firing rate <0.1 spikes/s) was evoked by a pulsed microiontophoretic ejection of glutamate. On striatal neurons, microiontophoretic application of SIN-1 induced a current-dependent inhibition (11/13), whereas l-NAME administration produced a clear excitation (9/9). On GP cells, the administration of SIN-1 had excitatory effects (10/15), whereas the administration of l-NAME reduced the neuronal activity (6/6). We hypothesize that NO could exert an intrinsic regulatory action on the activity of both striatal and GP cells. [Copyright &y& Elsevier]

The activity of single units in the striatum of urethane-anesthetized rats was recorded before and after the systemic administration of 7-nitro-indazole (7-NI; 50 mg/kg intraperitoneally), a selective inhibitor of neuronal nitric oxide (NO) synthase. Two neuronal types were clearly distinguishable electrophysiologically, on the basis of either discharge frequency pattern or features of the individual spike waveform (spike duration, negative phase/total duration ratio, and negative phase/total amplitude ratio). Only sporadically discharging neurons (basal firing rate, <0.1 spikes/s) were influenced by 7-NI, which caused a statistically significant increase in their firing rate. In contrast, the activity of continuously discharging neurons (basal firing rate, 4–6 spikes/s) was not affected. We hypothesize that NO neurotransmission could exert a tonic inhibitory influence upon sporadically discharging striatal neurons, which are presumably striatal output neurons. [Copyright &y& Elsevier]

• BL/BLI combination was the most common antibiotic regimen used for Enterobacteriaceae bloodstream infection (E-BSI). • All-cause 30-day mortality rate was low (6.8%) in patients receiving appropriate empirical/definitive BL/BLI therapy. • Non-susceptibility to ESCs was not associated with increased 30-day mortality or higher 90-day relapse rate. • In multivariate analysis, the only predictor of relapse was immunosuppression, mainly in patients with higher SOFA score. The aim of this study was to investigate risk factors for treatment failure in patients receiving in vitro-active therapy with β-lactam/β-lactamase inhibitor (BL/BLI) for Enterobacteriaceae bloodstream infection (E-BSI). This was a retrospective, single-centre study of patients diagnosed with E-BSI at an Italian centre over a 4-year period. Exclusion criteria were age <18 years, clinical data unavailable, polymicrobial BSI, failure to receive in vitro-active therapy and death within 72 h from drawing the index blood culture. Patients who received BL/BLI as appropriate empirical and/or definitive therapy for ≥50% of the total treatment duration were selected. The primary endpoint was all-cause 30-day mortality. The secondary endpoint was 90-day relapse. Of 1319 eligible patients, 835 were selected. A total of 714 received BL/BLI as appropriate empirical therapy, of whom 522 remained on BL/BLI as definitive therapy and 192 shifted to another antibiotic for <50% of the treatment duration; 121 received BL/BLI as definitive therapy only. Non-susceptibility to extended-spectrum cephalosporins (NS-ESCs) was detected in 207 episodes (24.8%). All-cause 30-day mortality was 6.8%. In multivariate analysis adjusted for NS-ESC, independent predictors of mortality were Charlson comorbidity index, septic shock, Proteus spp. and CVC-related BSI, whilst urinary source was a protective factor. The 90-day relapse rate was 4.2%. Immunosuppression was the main independent predictor for relapse. BL/BLI was the most common antibiotic administered to patients with E-BSI in this cohort. Among patients appropriately treated with BL/BLI, failure rates were low and were primarily associated with underlying diseases, clinical severity at BSI onset and infection source. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a fascinating signalling molecule implicated in a plethora of biological functions, especially at the synaptic level. Exploring neurotransmission in the hippocampus could be instrumental in the individuation of putative targets for nitric-oxide mediated neuromodulation, especially in terms of the potential repercussions on fundamental processes i.e. synaptic plasticity and excitability-related phenomena. Among these targets, endovanilloid signalling constitutes an object of study since Transient Receptors Vanilloid type 1 (TRPV1) channels possess a NO-sensitive gate modulating its activation. Also, NO has been referred to as a mediator for numerous endocannabinoid effects. Notwithstanding, the linkage between TRPV1 and NO systems in neuromodulation still remains elusive. To this end, we aim at investigating the involvement of TRPV1 in nitric oxide-mediated influence on hippocampal processes. Electrophysiological whole-cell recordings in CA1 pyramidal neurons were applied to evaluate excitatory neurotransmission in rat brain slices. Indeed, miniature excitatory postsynaptic currents (mEPSCs) were analysed upon pharmacological manipulation of TRPV1 and NO signalling pathways. In detail, only the administration of the specific TRPV1 exogenous agonist – capsaicin - reduced the frequency and amplitude of mEPSC similarly to the inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitroindazole (7NI). In contrast, capsazepine, TRPV1 antagonist, does not influence excitatory transmission. The combined TRPV1 activation and nNOS blockade confirm the presence of a putative common mechanism. When we administered the endovanilloid-endocannabinoid ligand, i.e. anandamide, we unveiled a potentiation of neurotransmission that was selectively reverted by 7NI. Our data suggest that nitric oxide influences TRPV1 hippocampal signalling since these channels are not constitutively active, but can be "on-demand" activated to modulate excitation in CA1 pyramidal neurons, and that this effect is linked to nitric oxide production. [Display omitted] • Nitric oxide production modulates excitatory transmission in CA1 pyramidal neurons. • TRPV1 influence nitrergic modulation of miniature excitatory post-synaptic currents. • Nitrergic intracellular levels are correlated with on-demand TRPV1-CB1 signaling. [ABSTRACT FROM AUTHOR]

Highlights: [•] Pregnenolone sulphate facilitates the acquisition of spatial information. [•] Pregnenolone sulphate enhances simple and complex object discrimination. [•] Pregnenolone sulphate increases hippocampal and perirhinal neuronal firing. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The effects of local applied NO-active compounds on glutamate (GLU)-evoked responses were investigated in globus pallidus (GP) neurons. Main methods: Extracellularly recorded single units from anesthetized rats were treated with GLU before and during the microiontophoretic application of S-nitrosoglutathione (SNOG), a NO donor, and Nω-nitro-l-arginine methyl ester (L-NAME), a NOS inhibitor. Key findings: Most GP cells were excited by SNOG whereas administration of L-NAME induced decrease of GP neurons activity. Nearly all neurons responding to SNOG and/or L-NAME showed significant modulation of their excitatory responses to the administration of iontophoretic GLU. In these cells, the changes induced by NO-active drugs in the magnitude of GLU-evoked responses were used as indicators of NO modulation. In fact, when a NO-active drug was co-iontophoresed with GLU, significant changes in GLU-induced responses were observed: generally, increased magnitudes of GLU-evoked responses were observed during SNOG ejection, whereas the administration of L-NAME decreased responses to GLU. Significance: The results suggest that the NO-active drugs modulate the response of GP neurons to glutamatergic transmission. Nitrergic modulation of glutamatergic transmission could play an important role in the control of GP bioelectric activity, considered a fundamental key in the BG function. [Copyright &y& Elsevier]