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Noise-induced hearing loss (NIHL) is responsible for significant adverse effects on cognition, quality of life and work, social relationships, motor skills, and other psychological aspects. The severity of NIHL depends on individual patient characteristics, sound intensity, and mainly the duration of sound exposure. NIHL leads to the production of a reactive oxygen (ROS) inflammatory response and the activation of apoptotic pathways, DNA fragmentation, and cell death. In this situation, antioxidants can interact with free radicals as well as anti-apoptotics or anti-inflammatory substances and stop the reaction before vital molecules are damaged. Therefore, the aim of this study was to analyze the effects of different pharmacological treatments, focusing on exogenous antioxidants, anti-inflammatories, and anti-apoptotics to reduce the cellular damage caused by acoustic trauma in the inner ear. Experimental animal studies using these molecules have shown that they protect hair cells and reduce hearing loss due to acoustic trauma. However, there is a need for more conclusive evidence demonstrating the protective effects of antioxidant/anti-inflammatory or anti-apoptotic drugs' administration, the timeline in which they exert their pharmacological action, and the dose in which they should be used in order to consider them as therapeutic drugs. Further studies are needed to fully understand the potential of these drugs as they may be a promising option to prevent and treat noise-induced hearing loss.

Crop diversification can enhance farm economic sustainability while reducing the negative impact on the environment and ecosystem services related. Despite the market and non-market benefits of crop diversification, monocropping is a widely used dominant practice in Europe. In this context, this works aims to assess the overall economic impact of several crop diversification systems across Europe and compared it to the monocropping system. For this purpose, an economic valuation by integrating market and non-market values for eight case studies distributed across three different European pedoclimatic regions (Southern Mediterranean, Northern Mediterranean and Boreal) is proposed. The economic valuation was conducted both in the short and medium-long term. For the short-term we conducted a social gross margin analysis, while for the medium-long term a cost-benefit analysis is developed. The results show an improvement in social gross margins for most of the diversification scenarios assessed when environmental and socio-cultural benefits are considered in the short-term. In the medium and long-term the transformation of cropping towards a more diversified agriculture is encouraged by greater economic benefits. These results provide a first insight in global economic performance of diversified cropping systems, whose main contribution relies on the integration of market and non-market values of ecosystem services from crop diversification. They are expected to be useful for guiding policy makers to promote crop diversification practices as a key instrument for building resilience in farming systems for an adaptive management to climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of the ecosystem services approach for ecosystem management, including the valuation of ecosystem services, has grown in recent decades. Although a common framework is used, each ecosystem has its own characteristics. The agroecosystem, for example, is an anthropised ecosystem where ecosystem service flows are highly interrelated with the environment, positively or negatively. Therefore, agroecosystem services are usually accompanied by disservices. The valuation of agroecosystem services and disservices requires adaptation of existing ecosystem services paradigms to accommodate the innate agroecosystem idiosyncrasies. To this end, in this study, a comprehensive approach for valuation of agroecosystem services and disservices was proposed and validated in a semi-arid western Mediterranean agricultural area through stakeholder assessment, using a choice experiment. The results suggest that all categories of services (provisioning, regulating, and cultural) should be taken into account when valuing agroecosystem services and disservices. In particular, food provision (a provisioning service), water (a provisioning disservice), local climate regulation and biodiversity (regulating services), waste treatment and water purification (regulating disservices), and recreation and tourism (cultural services) are relevant for this purpose. Their relative importance in agroecosystems valuation reached 70% for agroecosystem services and 30% for disservices. Specifically, biodiversity (38%) emerged as the most relevant agroecosystem service to be valued, followed by recreation and tourism (20%), local climate regulation (7%), and food provision (5%). Among the agroecosystem disservices, water and waste treatment (15%), and water purification (15%) together contributed to 30% of the total importance. Agroecosystems should be valued considering their multifunctional character and the integration of agroecosystem services and disservices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Bacillus Calmette-Guérin (BCG) maintenance therapy for 3 yr following BCG induction can reduce the progression of urothelial bladder carcinoma versus BCG induction alone, but is associated with high toxicity., Objective: To investigate whether a modified 3-yr BCG maintenance regimen following induction therapy is more effective than standard BCG induction therapy alone and exhibits a low toxicity profile., Design, Setting, and Participants: Patients from the outpatient clinics of the participating centres with high-risk non-muscle-invasive bladder carcinoma (NMIBC) were randomised between October 1999 and April 2007., Intervention: Participants received BCG induction once-weekly for 6 wk (no maintenance arm) or BCG induction followed by one BCG instillation every 3 mo for 3 yr (maintenance arm)., Outcome Measurements and Statistical Analysis: Primary endpoints were disease-free interval (DFI) and time to progression (TTP). Secondary endpoints included survival duration and toxicity. Differences between treatment arms were tested using Student's t test and χ(2) and log-rank tests., Results and Limitations: A total of 397 patients were randomised, 195 to the no-maintenance and 202 to the maintenance arm. A median time to recurrence was not reached in either treatment arm. DFI was similar between the arms (hazard ration [HR] 0.83; 95% CI 0.61-1.13; p=0.2) with disease relapse at 5 yr of 33.5% and 38.5%, respectively. TTP was also similar between the treatment arms (HR 0.79; 95% CI 0.50-1.26; p=0.3), with a progression rate at 5 yr of 16% and 19.5%, respectively. There were no significant differences between the treatment groups for overall survival and cancer-specific survival at 5 yr. Twenty and five patients in the maintenance and no-maintenance arms, respectively, stopped treatment because of toxicity. The most common local side effects were frequency (65% of patients), dysuria (63%), and haematuria (43%); the most frequent systemic side effects were general malaise (7.2%) and fever (34%)., Conclusions: In NMIBC patients treated with maintenance therapy comprising a single BCG instillation every 3 mo for 3 yr following standard induction BCG, we did not observe a decrease in recurrence and progression rates versus induction therapy alone., Patient Summary: Patients who undergo surgery to remove bladder cancer are usually treated with bacillus Calmette-Guérin (BCG) for 6 wk if there is a high risk of disease recurrence. Extending BCG therapy by 3 yr can further minimise disease recurrence and progression, but is associated with more side effects. We report that a modified 3-yr BCG treatment regimen showed low toxicity, but seemed to be no more effective than 6-wk treatment., Trial Registration: CUETO 98013., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Intravesical bacillus Calmette-Guérin (BCG) is an effective therapy in non-muscle-invasive bladder cancer (NMIBC), but it has limitations in terms of recurrence and toxicity., Objective: To determine whether the sequential combination of mitomycin C (MMC) and BCG is superior to BCG alone in increasing a disease-free interval (DFI)., Design, Setting, and Participants: We conducted a prospective randomized trial including 407 patients with intermediate- to high-risk NMIBC and allocated 211 to the MMC and BCG arm and 196 to the BCG-alone arm., Outcome Measurements and Statistical Analysis: The trial was designed to provide concurrently a power of 80% for the detection of a relative risk reduction of 35% (hazard ratio [HR]: 0.65) of disease relapse with a type I error of 0.05. Times to events were estimated using cumulative incidence functions and compared using the Cox regression model. We used the Kaplan-Meier technique to estimate survival curves., Results and Limitations: In the intention-to-treat analysis at 5 yr, DFI was significantly improved by the sequential scheme (HR: 0.57; 95% confidence interval [CI], 0.39-0.83; p=0.003), reducing the disease relapse rate from 33.9% to 20.6%. Higher toxicity was observed with the combination, even reducing the MMC dose, especially in G3 local toxicity compared with BCG with a difference of 17.4% (95% CI, 7.6-27.2; p<0.001). In recurrent T1 tumors, the potential benefit of the sequential scheme was more evident than in the remaining subgroup (18.8% vs 12.8%), with a number needed to treat of five versus eight to avoid an event and with similar toxicity., Conclusions: Although the sequential scheme is more effective than BCG alone in reducing disease relapse, due to higher toxicity it could be offered only to patients with a high likelihood of recurrence, such as those with recurrent T1 tumors., Patient Summary: We analyzed the outcomes of a randomized trial demonstrating that in intermediate- to high-risk non-muscle-invasive bladder cancer, mitomycin C and bacillus Calmette-Guérin (BCG) reduced disease relapse compared with BCG alone but was more toxic. Consequently, it could be offered only to patients with recurrent T1 tumors., Trial Registration: CUETO 93009., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The shortage of organ availability in recent years has made it necessary to use grafts from advanced-aged donors to maintain the rate of renal transplantation in our country. The objective of this study was to evaluate the graft function and patient survival using kidneys from deceased donors of over 65 year of age. From 2005 until 2010, we compared the outcomes of patients who received grafts from donors over 65 years old vs less than 65 years. We observed no significant difference in sex, time on dialysis, or cold ischemia time between the groups. As expected the recipient age was significantly different. For the analysis of survival, we used the Tablecloth-Haenzel test and the Kaplan-Meier survival estimator. Actuarial survivals at 3 years after transplantation showed 84.8% among patients transplanted with kidneys from donors over 65 years old versus 97.5% in the control group. The graft survival was 78.8% among expanded criteria versus 86.85% in the control group. When we analyzed graft survival using an "exitus-censured" analysis, we obtained graft survivals of 89.1% in the expanded criteria kidney group versus 88.6% among the controls. We concluded that the use of kidney from donors over 65 years of age allows us to increase the rate of renal transplantation to about 15 to 20 per million population, with good graft and patient survivals provided that the protocol for expanded criteria organs ensured proper macroscopic and microscopic evaluation of the organ for transplantation., (Copyright © 2011. Published by Elsevier Inc.)

Painful legs and moving toes is a rare syndrome characterized by spontaneous neuropathic pain in the lower limbs associated with peculiar involuntary movements of the lower extremities, especially the toes and feet. Although its origin is unknown, it is associated to some pathologies. With regard to the painless variant, very few patients have been reported and most of them are idiopathic. We report a patient with involuntary movements of the toes similar to those seen in painful legs and moving toes syndrome, but without any associated pain and due to a spinal compression. We conclude that spinal lesions may produce the painless variant as it has been reported with the painful form.

Introduction: Intracranial hypertension is a picture characterized by elevated cerebrospinal fluid pressure that may cause some different complications including optic disc edema and visual accuracy alterations. Although treatment is generally pharmacological, invasive therapeutical techniques such as optic nerve sheath fenestration and lumboperitoneal shunt are sometimes required. The latter one is a technique that usually provides good results with a low complication rate, including infections, mechanical failure and overdrainage., Case Report: We report the case of a 40 year-old female patient with an idiopathic intracranial hypertension picture who required a lumboperitoneal shunt due to her progressive deterioration. After a few hours, the patient developed an intracerebral hematoma and subarachnoid hemorrhage, and some days later she developed a venous sinus thrombosis. These two complications, although described in the literature, are very unusual., Conclusions: Even though the lumboperitoneal shunt is a safe technique with good results, it is not exempt from complications. We alert about the need to take into account subarachnoid hemorrhage and venous sinus thrombosis as possible complications in the followup of these patients.

The paper aims to present the case of a progressive and unilateral cranial polyneuropathy due to perineural spread of cutaneous squamous cell carcinoma. This is a case of a 73 year old man with a history of squamous cell carcinoma in the right temporal region that was removed in 1992. In May 2000 he first presented pain and numbness in the distribution of the first branch of right trigeminal nerve and weakness of the ipsilateral frontal muscle. Later on he presented right ophthalmoplegia, and damage of lower cranial nerves, leading to dysphagia and respiratory distress. He was admitted in March 2001 for a gastrostomy for feeding, when ataxia and recurrence of the right temporal lesion ensued. After three examinations with MRI, the fourth study showed meningeal carcinomatous and a metastatic lesion in the brainstem. Histopathologic examination demonstrated dermal and perineural invasion by squamous cell carcinoma. The necropsy also showed meningeal, perineural and endoneural infiltration of atypical epidermal cells and a pons mass composed of the same cells. We conclude that the perineural spread of the cutaneous carcinoma is an exceptional cause of cranial neuropathy, however it must be ruled out in patients with progressive and unilateral cranial neuropathy. In these cases, when no radiological abnormalities are noted, a biopsy may be performed on the peripheral branches of the cranial nerve to confirm the diagnosis.

Introduction: The place of platelet antiaggregants in the aetiology of intracerebral hemorrhage (IH) has not been extensively studied., Objective: To analyze the characteristics of IH in patients treated with platelet antiaggregants and the possible clinical and prognostic differences from other primary IH., Patients and Methods: A retrospective study of patients admitted to hospital with primary IH from 1985 to 1997. The cases were IH patients while being treated with platelet antiaggregants. For each case we selected two controls with IH and similar age and IH risk factors. The following data was analyzed: start of clinical condition; type, dose, indication and duration of treatment with antiaggregants; mortality, localization, volume and extension of IH to the ventricles. The last four variables were compared with the control group using the ji squared test (chi 2) and the t student test., Results: 21one patients had a primary IH while being treated with antiaggregants: 20 with salicylates (17 aspirin and 3 riflusal) and one with ticlopidine. The dose of aspirin was 500 mg or less in 90% of the cases. In the group treated with salicylates, this was given for more than 20 months in 90% of the cases. Initially there was no clinical progression in any case. No significant differences were observed between the variable compared, although there was a tendency to greater volume, extension to the ventricles and mortality in the group treated with antiaggregants., Conclusions: More studies with larger numbers of patients are necessary to be able to confirm the tendencies observed.

The presence of intracranial hemorrhage with a fluid-blood level in patients receiving anticoagulant medication or with coagulopathy is an infrequent but well-documented complication. We reported a patient with a fluid-blood level with normal haemostasis. A 62-year-old-man was admitted with a left putaminal hemorrhage containing a fluid-blood level, but without abnormal haemostasis. Five months later the patient returned to the hospital because of a transient ischemic attack. A cranial CT demonstrated a hypodensity in the left putamen nucleus and corona radiata. Electrocardiogram revealed atrial fibrillation and a cardiac ultrasonographic examination showed mitral annulus calcification and left atrial enlargement. The finding of intracranial fluid-blood level has been seen in patients with arteriovenous malformations, primary and metastatic neoplasm, radiation-induced necroses, cerebral amyloid angiopathy, intrainfarct hematoma and without any identified aetiology. We suggest that in our patient this disorder was due to a intrainfarct hematoma.

A 34-year-old man, recently diagnosed as diabetic, presented an acute painful neuropathy. He reported a profound weight loss during the months preceding onset. There were no motor symptoms, and only mild neurological signs were observed on examination. Improvement was related to a good glycemic control and weight gain. Acute painful diabetic neuropathy is a condition that may affect diabetic patients shortly after development of the disease. The pathogenetic roles played by different factors are reviewed.

Progressive myoclonus epilepsy of the Lafora type (Lafora's disease) is an autosomal recessive disease characterized by epilepsy, myoclonus, dementia, and periodic acid-Schiff-positive intracellular inclusion bodies. The inclusion deposits consist of branched polysaccharides (polyglucosans) but the responsible biochemical defect has not been identified. Onset is during late childhood or adolescence and the disease leads to a fatal outcome within a decade of first symptoms. We studied nine families in which Lafora's disease had been proven by biopsy in at least one member. In order to locate the responsible gene, we screened the human genome with microsatellite markers spaced an average of 13 cM. We used linkage analysis in all nine families and homozygosity mapping in four consanguineous families to define the Lafora's disease gene region. Two point linkage analysis resulted in a total peak lod score of 10.54 for marker D6S311. Six additional chromosome 6q23-25 microsatellites yielded lod scores ranging from 5.92 to 9.60 at theta m = f = 0. An extended pedigree with five affected members independently proved linkage with peak lod scores over 3.8 at theta m = f = 0 for D6S292, D6S403, and D6S311. The multipoint one-lod-unit support interval covered a 2.5 cM region surrounding D6S403. Homozygosity mapping defined a 17 cM region in chromosome 6q23-25 flanked by D6S292 and D6S420 that contains the Lafora's disease gene.

Since this is a systemic disease, it is not uncommon to find brucella organisms in urine during acute infection however, it frequently presents with orchi-epididymitis (2-20%) and, rarely, with granulomas in the urinary tract. We report on two cases of acute epididymitis. The pathogenesis, diagnosis and treatment of this disease entity are briefly viewed highlighting the urological problem.

A case of perineal-scrotal and hypogastric pain following coitus interruptus in a young male patient is described. The physiopathological mechanisms involved in this condition in normal subjects or those with neuropathic disorders are discussed.