Shrimp Waste Upcycling: Unveiling the Potential of Polysaccharides, Proteins, Carotenoids, and Fatty Acids with Emphasis on Extraction Techniques and Bioactive Properties.

Shrimp processing generates substantial waste, which is rich in valuable components such as polysaccharides, proteins, carotenoids, and fatty acids. This review provides a comprehensive overview of the valorization of shrimp waste, mainly shrimp shells, focusing on extraction methods, bioactivities, and potential applications of these bioactive compounds. Various extraction techniques, including chemical extraction, microbial fermentation, enzyme-assisted extraction, microwave-assisted extraction, ultrasound-assisted extraction, and pressurized techniques are discussed, highlighting their efficacy in isolating polysaccharides, proteins, carotenoids, and fatty acids from shrimp waste. Additionally, the bioactivities associated with these compounds, such as antioxidant, antimicrobial, anti-inflammatory, and antitumor properties, among others, are elucidated, underscoring their potential in pharmaceutical, nutraceutical, and cosmeceutical applications. Furthermore, the review explores current and potential utilization avenues for these bioactive compounds, emphasizing the importance of sustainable resource management and circular economy principles in maximizing the value of shrimp waste. Overall, this review paper aims to provide insights into the multifaceted aspects of shrimp waste valorization, offering valuable information for researchers, industries, and policymakers interested in sustainable resource utilization and waste-management strategies.

Anti-SARS-CoV-2 T-stem cell memory persists in ocrelizumab-treated MS patients.

BACKGROUND: Development of long-lasting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) T-cell responses in persons with multiple sclerosis (pwMS) treated with ocrelizumab is questioned. OBJECTIVE: Investigate antiviral T-cell responses after infection with SARS-CoV-2 in ocrelizumab-treated pwMS. Control groups included ocrelizumab-treated pwMS without SARS-CoV-2 infection, and non-MS individuals with and without SARS-CoV-2 infection. METHODS: Peripheral blood mononuclear cells were stimulated with SARS-CoV-2 peptide pools and T-cell reactivity was assessed by ELISPOT for interferon (IFN)-γ detection, and by multiparametric fluorescence-activated cell sorting (FACS) analyses for assessment and characterization of T-cell activation. RESULTS: ELISPOT assay against the spike and the N protein of SARS-CoV-2 displayed specific T-cell reactivity in 28/29 (96%) pwMS treated with ocrelizumab and infected by SARS-CoV-2, similar to infected persons without MS. This reactivity was present 1 year after infection and independent from the time of ocrelizumab infusion. FACS analysis following stimulation with SARS-CoV-2 peptide pools showed the presence of activation-induced markers (AIMs) in both CD4+ and CD8+ T-cell subsets in 96% and 92% of these individuals, respectively. Within naïve AIM+ CD4+ and CD8+ T-cells, we detected T memory stem cells, suggesting the acquisition of long-term memory. CONCLUSIONS: B-cell depletion using ocrelizumab does not impair the development of long-lasting anti-SARS-CoV-2 T-cell responses.

Partial Gastrectomy at the Time of Splenectomy in Two Dogs With Splenic Neoplasia and Gastric Involvement.

Splenic malignancies are reported in 30%-76% of dogs presenting with splenic masses, and splenectomy is the cornerstone in their management. However, long term prognosis is guarded due to the high rates of distant metastases reported both for HSA and nonangiogenic nonlymphomatous sarcomas. Metastases from splenic tumors usually occur to regional lymph nodes, liver, omentum, and lungs. These case series aim to describe 2 cases of splenic neoplasia with gastric involvement and report the surgical technique and outcomes associated with the condition. Two mixed-breed dogs were referred for a splenic mass and underwent explorative celiotomy. In both cases, the splenic mass was firmly attached to the gastric wall, and splenectomy with concurrent partial gastrectomy was thus performed. In case 1, liver lobectomy due to a hepatic mass was also performed. In case 2, the regional nodes were also excised due to lymphoadenomegaly. Both dogs recovered uneventfully from surgery and were discharged from the hospital at 72 and 96 hours. Histopathological examination was costent with splenic undifferentiated sarcoma and hepatic adenocarcinoma in one dog. The other dog had a diagnosis of malignant fibrous histiocytoma with nodal metastases. Neoplastic invasion of the stomach was histologically confirmed in both dogs. Adjuvant chemotherapy was refused, and both dogs were euthanized due to tumor progression at 71 and 58 days, respectively. According to our results, splenectomy with concurrent gastrectomy is feasible in dogs with splenic tumours involving the gastric wall. However, long term prognosis is poor, as previously reported for metastatic splenic sarcomas.

Switching to ocrelizumab in RRMS patients at risk of PML previously treated with extended interval dosing of natalizumab.

Discontinuation of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) at risk of progressive multifocal leukoencephalopathy (PML) is associated with disease reactivation. Forty-two RRMS patients, who switched from an extended interval dose (EID) of natalizumab to ocrelizumab, underwent magnetic resonance imaging (MRI) and clinical monitoring during washout and after ocrelizumab starting. During the first 3 months, disease reactivation was observed in five (12%) patients; 6 months after ocrelizumab starting, no further relapses were recorded, and Expanded Disability Status Scale (EDSS) remained stable in 38 (90%) patients. In conclusion, ocrelizumab could be considered a choice to mitigate the risk of disease reactivation in patients previously treated with natalizumab-EID.

Impact of natural menopause on multiple sclerosis: a multicentre study.

OBJECTIVE: To study the effect of natural menopause on multiple sclerosis clinical course. METHODS: This was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status. RESULTS: 148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059). CONCLUSION: Natural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

Four cases of natalizumab-related PML: a less severe course in extended interval dosing?

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe adverse event of natalizumab (NTZ). The administration of NTZ with extended interval dosing (EID) has been proposed as a strategy to potentially reduce the incidence of PML while maintaining its therapeutic efficacy. METHODS: In the current paper, we describe 4 cases of NTZ-PML in EID included in the Italian PML cohort. RESULTS: The patients developed PML after at least 38 NTZ infusions. Their John Cunningham virus (JCv) index was > 1.5, and patients had not previously used immunosuppressant. Two patients were asymptomatic at PML onset, while two had mild motor impairment of the right hand and anomia, respectively. All of them had undetectable viral load but one (37 JCv copies/ml). In all patients, MRI revealed unilobar lesions with deferred contrast enhancement suggestive of immune reconstitution. The clinical course ended with a favorable clinical outcome (ΔEDSS up to 1). CONCLUSIONS: Although PML in EID seems to occur less frequently than in conventional dosing regimen, strict monitoring of high-risk patients contributed to the indolent course observed in the four described cases, characterized by a prolonged pre-symptomatic phase, paucisymptomatic onset, low JCv load, less severe functional impairment during immune reconstitution, and a mild disability burden.

To do or not to do? plasma exchange and timing of steroid administration in progressive multifocal leukoencephalopathy.

OBJECTIVE: To retrospectively analyze the effect of plasma exchange (PLEX; yes = PLEX+ , no = PLEX- ) and steroids administration timing (prophylactically [proST] or therapeutically [therST]) on the longitudinal clinical course of patients with natalizumab-related progressive multifocal leukoencephalopathy (PML) and full-blown immune reconstitution inflammatory syndrome (PML-IRIS). METHODS: Clinical and radiological data of 42 Italian patients with PML were analyzed. Patient's data are available until 12 months after PML diagnosis. PLEX and steroids treatment as time-dependent covariates were entered in: (1) a Cox model to investigate their impact on full-blown PML-IRIS latency; (2) an analysis of variance ANOVA to investigate their impact on IRIS duration; and (3) a linear mixed model to assess their impact on the longitudinal clinical course (measured by means of Expanded Disability Status Scale [EDSS]). RESULTS: Treatment with PLEX was not associated to PML-IRIS latency (hazard ratio [HR] = 1.05; p = 0.92), but once IRIS emerged, its duration was significantly longer in patients who underwent PLEX (101 vs 54 days in PLEX+ and PLEX- patients; p = 0.028). Receiving proST versus therST was not associated to IRIS latency (HR = 0.67; p = 0.39) or duration (p = 0.95). Patients who underwent proST had a significantly higher EDSS increase during PML (0.09 EDSS points per month; p = 0.04) as compared to those who had therST. INTERPRETATION: This study highlights that: (1) caution on the use of PLEX should be considered as the current data do not support a beneficial effect of PLEX and (2) caution on the early use of steroids is suggested because their prophylactic use to prevent full-blown PML-IRIS seems to negatively impact on the longitudinal disability course. Ann Neurol 2017;82:697-705.

Association Between BKPyV Serotype I Antibody Level and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy.

To determine the association between BK polyomavirus (BKPyV) types 1 and 4 capsid antibody and natalizumab-associated progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS), serum samples were obtained from 10 natalizumab-associated PML cases and 130 control MS patients treated with natalizumab, and 82 control MS patients never exposed to natalizumab. In a sex- and age-adjusted regression model, BKPyV serotype 1 antibody levels were significantly higher in natalizumab-treated controls (p = 0.009) compared with cases, and were higher in controls never treated with natalizumab compared with cases, but the difference did not reach statistical significance (p = 0.158). There was no association between BKPyV serotype 4 antibody and PML. We hypothesize that a robust immune response to BKPyV may be protective against the development of PML.

Age as a risk factor for early onset of natalizumab-related progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare but potentially fatal opportunistic infection that arises almost exclusively in immunocompromised patients or in those treated with monoclonal antibodies, especially natalizumab. Here, we aimed at exploring if age at treatment start affects the time to onset of natalizumab-related PML. PubMed was searched for the terms "natalizumab and progressive multifocal leukoencephalopathy" in articles published from January 2005 to March 2017. We collected information on each identified PML case, including demographic and clinical variables at natalizumab start and at PML onset. The number of natalizumab infusions until PML onset was investigated in time-to-event analyses. We identified 238 cases who developed PML after a median number of 33 natalizumab infusions (range 6 to 103). Risk factors for an earlier onset of natalizumab-related PML were prior immunosuppressant exposure (hazard ratio [HR] = 1.43, p = 0.017) and older age at treatment start (HR = 1.02, p = 0.016). In particular, patients older than 50 years had a more than doubled-increased risk for an earlier PML onset (HR = 2.11, p = 0.006). Our findings suggest that the age at natalizumab start may represent a risk factor for an earlier PML onset, thus claiming further investigations about the interplay between immunosenescence and MS treatments.

Is maraviroc useful in multiple sclerosis patients with natalizumab-related progressive multifocal leukoencephalopathy?

BACKGROUND: Despite the recent advances in the understanding of natalizumab (NTZ) related progressive multifocal leukoencephalopathy (PML) and its associated immune reconstitution inflammatory syndrome (PML-IRIS), the therapeutic options are still under investigated. In this context, the beneficial use of maraviroc is still an anecdotal observation. OBJECTIVE: To evaluate the impact of maraviroc in modifying the course of PML preventing IRIS or blunting IRIS manifestations. METHODS: Three patients with NTZ PML included in the Italian dataset of PML were treated with maraviroc. Their longitudinal clinical and radiological course was described in detail. RESULTS: The three patients were characterized by a steady clinical worsening not controlled by maraviroc. All the three patients manifested PML-IRIS, which emerged, respectively, at 62, 64 and 90days post NTZ withdrawal. This is in accordance with the data of the Italian dataset. Clinical and radiological stabilization of PML-IRIS occurred only after corticosteroids administration. CONCLUSION: In these three cases, maraviroc did not show any clear effect in modulating the clinical course of PML preventing IRIS. Moreover, once PML-IRIS emerged, the clinical stabilization was achieved only with the use of corticosteroids. Thus, the use of maraviroc should be regarded with extreme caution due the potential adverse events associated with its use.

No evidence of beneficial effects of plasmapheresis in natalizumab-associated PML.

OBJECTIVE: To examine retrospectively the effects of plasmapheresis (PLEX) on the survival and clinical outcomes of patients with multiple sclerosis (MS) and natalizumab (NTZ)-associated progressive multifocal leukoencephalopathy (PML). METHODS: The medical literature was searched for the terms natalizumab and progressive multifocal leukoencephalopathy. A total of 193 international and 34 Italian NTZ-PML cases were included. Clinical outcome was determined by comparing the patients' clinical status at PML diagnosis with status after PML resolution. The effects on survival and clinical outcome of PLEX, sex, age, country, pre-PML Expanded Disability Status Scale score, NTZ infusion number, prior immunosuppressant exposure, PML symptoms, PML lesion location at diagnosis, CSF JC virus status and copies, additional PML treatments and steroids, and PML immune reconstitution inflammatory syndrome (IRIS) development were investigated with both univariate and multivariate analyses. RESULTS: A total of 219 NTZ-PML cases were analyzed, and 184 (84%) underwent PLEX, which did not reduce the mortality risk or the likelihood of poor vs favorable outcomes. Country was predictive of mortality and poor outcome, while PML-IRIS development was predictive of poor outcome. CONCLUSIONS: PLEX did not improve the survival or clinical outcomes of Italian or international patients with MS and NTZ-PML, suggesting that this treatment should be performed cautiously in the future. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with NTZ-PML, PLEX does not improve survival. The study lacks the statistical precision to exclude an important benefit or harm of PLEX.

Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry.

BACKGROUND: The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV). OBJECTIVE: To describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions. METHODS: An Italian independent collaborative repository initiative collected and analyzed socio-demographic, clinical, magnetic resonance imaging (MRI) data and number of JCV-DNA copies detected on cerebrospinal fluid (CSF) samples of patients diagnosed as affected by NTZ-related PML. The evolution of disability, measured by the Expanded Disability Status Scale, was assessed at NTZ start, at PML diagnosis and after 2, 6 and 12 months from PML diagnosis. The effect of clinical and paraclinical characteristics at PML diagnosis on the final outcome was also investigated. RESULTS: Ten patients (25.6%) were diagnosed before 24 NTZ infusions. In six cases (15.4%) the PML suspect was made on the basis of highly suggestive MRI findings in absence of any detectable change of clinical conditions (asymptomatic PML). In patients with symptomatic PML, the diagnosis was quicker for those who presented with cognitive symptoms (n = 12) rather than for those with other neurological pictures (n = 21) (p = 0.003). Three patients (7.7%) died during the 12-month observation period, resulting in a survival rate of 92.3%. Asymptomatic PML, more localized brain involvement and gadolinium-enhancement detected at MRI, as well as lower viral load were associated with a better disability outcome (p-values<0.01). CONCLUSION: Our findings support that early PML diagnosis, limited CNS involvement and initial signs of immune restoration are associated with a better outcome and higher survival rate, and confirm the utility of MRI as a surveillance tool for NTZ-treated patients.

Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS) Patients during Treatment with Natalizumab.

The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment.

Percutaneous distal metatarsal osteotomy for correction of hallux valgus. Surgical technique.

BACKGROUND: Distal osteotomy of the first metatarsal is indicated for the surgical treatment of mild-to-moderate hallux valgus deformity. The aim of this study was to evaluate the results of a subcapital distal osteotomy of the first metatarsal with use of a percutaneous technique. METHODS: From 1996 to 2001, 118 consecutive percutaneous distal osteotomies of the first metatarsal were performed for the treatment of painful mild-to-moderate hallux valgus in eighty-two patients. The patients were assessed with a clinical and radiographic protocol at a mean of 35.9 months postoperatively. The American Orthopaedic Foot and Ankle Society (AOFAS) hallux-metatarsophalangeal-interphalangeal scale was used for the clinical assessment. RESULTS: The patients were satisfied following 107 (91%) of the 118 procedures. The mean score on the AOFAS scale was 88.2 +/- 12.9 points. The postoperative radiographic assessments showed a significant change (p < 0.05), compared with the preoperative values, in the mean hallux valgus angle, first intermetatarsal angle, distal metatarsal articular angle, and sesamoid position. The valgus deformity recurred after three procedures (2.5%), the first metatarsophalangeal joint was stiff but not painful after eight (6.8%), and a deep infection developed after one (0.8%). The infection resolved with antibiotic therapy. CONCLUSIONS: The percutaneous technique proved to be reliable for the correct execution of a distal linear osteotomy of the first metatarsal for the correction of a painful mild-to-moderate hallux valgus deformity. The clinical results appear to be comparable with those obtainable with traditional open techniques, with the additional advantages of a minimally invasive procedure, a substantially shorter operating time, and a reduced risk of complications related to surgical exposure.

Percutaneous distal metatarsal osteotomy for correction of hallux valgus.

BACKGROUND: Distal osteotomy of the first metatarsal is indicated for the surgical treatment of mild-to-moderate hallux valgus deformity. The aim of this study was to evaluate the results of a subcapital distal osteotomy of the first metatarsal with use of a percutaneous technique. METHODS: From 1996 to 2001, 118 consecutive percutaneous distal osteotomies of the first metatarsal were performed for the treatment of painful mild-to-moderate hallux valgus in eighty-two patients. The patients were assessed with a clinical and radiographic protocol at a mean of 35.9 months postoperatively. The American Orthopaedic Foot and Ankle Society (AOFAS) hallux-metatarsophalangeal-interphalangeal scale was used for the clinical assessment. RESULTS: The patients were satisfied following 107 (91%) of the 118 procedures. The mean score on the AOFAS scale was 88.2 +/- 12.9 points. The postoperative radiographic assessments showed a significant change (p < 0.05), compared with the preoperative values, in the mean hallux valgus angle, first intermetatarsal angle, distal metatarsal articular angle, and sesamoid position. The valgus deformity recurred after three procedures (2.5%), the first metatarsophalangeal joint was stiff but not painful after eight (6.8%), and a deep infection developed after one (0.8%). The infection resolved with antibiotic therapy. CONCLUSIONS: The percutaneous technique proved to be reliable for the correct execution of a distal linear osteotomy of the first metatarsal for the correction of a painful mild-to-moderate hallux valgus deformity. The clinical results appear to be comparable with those obtainable with traditional open techniques, with the additional advantages of a minimally invasive procedure, a substantially shorter operating time, and a reduced risk of complications related to surgical exposure.