An Investigation into the In Vitro Targeted Killing of CD44-Expressing Triple-Negative Breast Cancer Cells Using Recombinant Photoimmunotherapeutics Compared to Auristatin-F-Based Antibody-Drug Conjugates.

Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer with limited treatment options. The persistence of highly tumorigenic CD44-expressing subpopulation referred to as cancer stem cells (CSCs), endowed with the self-renewal capacity, has been associated with therapeutic resistance, hence clinical relapses. To mitigate these undesired events, targeted immunotherapies using antibody-photoconjugate (APC) or antibody-drug conjugate (ADC), were developed to specifically release cytotoxic payloads within targeted cells overexpressing cognate antigen receptors. Therefore, an αCD44(scFv)-SNAP-tag antibody fusion protein was engineered through genetic fusion of a single-chain antibody fragment (scFv) to a SNAPf-tag fusion protein, capable of self-conjugating with benzylguanine-modified light-sensitive near-infrared (NIR) phthalocyanine dye IRDye700DX (BG-IR700) or the small molecule toxin auristatin-F (BG-AURIF). Binding of the αCD44(scFv)-SNAPf-IR700 photoimmunoconjugate to antigen-positive cells was demonstrated by confocal microscopy and flow cytometry. By switching to NIR irradiation, CD44-expressing TNBC was selectively killed through induced phototoxic activities. Likewise, the αCD44(scFv)-SNAPf-AURIF immunoconjugate was able to selectively accumulate within targeted cells and significantly reduced cell viability through antimitotic activities at nano- to micromolar drug concentrations. This study provides an in vitro proof-of-concept for a future strategy to selectively destroy light-accessible superficial CD44-expressing TNBC tumors and their metastatic lesions which are inaccessible to therapeutic light.

Efficacy and safety of antiparasitic therapy for neurocysticercosis in rural Tanzania: a prospective cohort study.

PURPOSE: Neurocysticercosis is common in regions endemic for Taenia solium. Active-stage neurocysticercosis can be treated with antiparasitic medication, but so far no study on efficacy and safety has been conducted in Africa. METHODS: We conducted a prospective cohort study on treatment of neurocysticercosis in Tanzania between August 2018 and January 2022. Patients were initially treated with albendazole (15 mg/kg/d) for 10 days and followed up for 6 months. Additionally in July 2021, all participants who then still had cysts were offered a combination therapy consisting of albendazole (15 mg/kg/d) and praziquantel (50 mg/kg/d). Antiparasitic treatment was accompanied by corticosteroid medication and anti-seizure medication if the patient had experienced epileptic seizures before treatment. RESULTS: Sixty-three patients were recruited for this study, of whom 17 had a complete follow-up after albendazole monotherapy. These patients had a total of 138 cysts at baseline, of which 58 (42%) had disappeared or calcified by the end of follow-up. The median cyst reduction was 40% (interquartile range 11-63%). Frequency of epileptic seizures reduced considerably (p < 0.001). Three patients had all active cysts resolved or calcified and of the remaining 14, eight received the combination therapy which resolved 63 of 66 cysts (95%). Adverse events were infrequent and mild to moderate during both treatment cycles. CONCLUSION: Cyst resolution was unsatisfactory with albendazole monotherapy but was very high when it was followed by a combination of albendazole and praziquantel.

Bio-economic evaluation of a reduced phosphorus supplementation strategy for a cow-calf system in Brazil: a case study.

Fertility, weight of calves at weaning, and the economic aspects of a breeding herd receiving mineral supplements containing 75 or 12.5 g of phosphorus (P)/kg were measured from 2013 to 2016. No differences in reproduction parameters or weight at weaning were found before and after the adoption of the new scheme of mineral supplementation. Before the study, the annual cost with the formula containing more P was equivalent to 29.3 weaned beef calves; after the P reduction, the annual cost was equivalent to 2.2 to 6.8 weaned calves. After 3 years of supplementation with 12.5 g P/kg no signs of P deficiency were observed. The clinical-nutritional diagnosis of the herd indicated no cause-effect of P content of mineral supplements upon fertility or performance of healthy cows, demonstranting that the adequate forage allowance was enough to meet most P required by the cows.

Intranasal delivery of dexamethasone efficiently controls LPS-induced murine neuroinflammation.

Neuroinflammation is the hallmark of several infectious and neurodegenerative diseases. Synthetic glucocorticoids (GCs) are the first-line immunosuppressive drugs used for controlling neuroinflammation. A delayed diffusion of GCs molecules and the high systemic doses required for brain-specific targeting lead to severe undesirable effects, particularly when lifelong treatment is required. Therefore, there is an urgent need for improving this current therapeutic approach. The intranasal (i.n.) route is being employed increasingly for drug delivery to the brain via the olfactory system. In this study, the i.n. route is compared to the intravenous (i.v.) administration of GCs with respect to their effectiveness in controlling neuroinflammation induced experimentally by systemic lipopolysaccharide (LPS) injection. A statistically significant reduction in interleukin (IL)-6 levels in the central nervous system (CNS) in the percentage of CD45+ /CD11b+ /lymphocyte antigen 6 complex locus G6D [Ly6G+ and in glial fibrillary acidic protein (GFAP) immunostaining was observed in mice from the i.n.-dexamethasone (DX] group compared to control and i.v.-DX-treated animals. DX treatment did not modify the percentage of microglia and perivascular macrophages as determined by ionized calcium binding adaptor molecule 1 (Iba1) immunostaining of the cortex and hippocampus. The increased accumulation of DX in brain microvasculature in DX-i.n.-treated mice compared with controls and DX-IV-treated animals may underlie the higher effectiveness in controlling neuroinflammation. Altogether, these results indicate that IN-DX administration may offer a more efficient alternative than systemic administration to control neuroinflammation in different neuropathologies.

Interleukin 10 and dendritic cells are the main suppression mediators of regulatory T cells in human neurocysticercosis.

Neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. It is considered that, during co-evolution, the parasite developed strategies to modulate the host's immune response. The action mechanisms of regulatory T cells in controlling the immune response in neurocysticercosis are studied in this work. Higher blood levels of regulatory T cells with CD4(+) CD45RO(+) forkhead box protein 3 (FoxP3)(high) and CD4(+) CD25(high) FoxP3(+) CD95(high) phenotype and of non-regulatory CD4(+) CD45RO(+) FoxP3(med) T cells were found in neurocysticercosis patients with respect to controls. Interestingly, regulatory T cells express higher levels of cytotoxic T lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor (GITR), suggesting a cell-to-cell contact mechanism with dendritic cells. Furthermore, higher IL-10 and regulatory T cell type 1 (Tr1) levels were found in neurocysticercosis patients' peripheral blood, suggesting that the action mechanism of regulatory T cells involves the release of immunomodulatory cytokines. No evidence was found of the regulatory T cell role in inhibiting the proliferative response. Suppressive regulatory T cells from neurocysticercosis patients correlated negatively with late activated lymphocytes (CD4(+) CD38(+) ). Our results suggest that, during neurocysticercosis, regulatory T cells could control the immune response, probably by a cell-to-cell contact with dendritic cells and interleukin (IL)-10 release by Tr1, to create an immunomodulatory environment that may favour the development of T. solium cysticerci and their permanence in the central nervous system.

Immunopathology in Taenia solium neurocysticercosis.

Neurocysticercosis is a clinically and radiologically heterogeneous disease, ranging from asymptomatic infection to a severe, potentially fatal clinical picture. The intensity and extension of the parasite-elicited inflammatory reaction is a key factor for such variability. The main features of the inflammatory process found in the brain and in the peripheral blood of neurocysticercosis patients will be discussed in this review, and the factors involved in its modulation will be herein presented.

Report of three patients with extensive neurocysticercosis in rural southern Tanzania: neurological, serological and neuroradiological findings.

BACKGROUND: Neurocysticercosis (NCC) is common in eastern Africa, but disease presentation varies considerably. Most patients have single or few NCC-typical lesions in their brain but some present with a large number of lesions. We present three patients with positive antibody-based serology for Taenia solium cysticercosis screened at the Vwawa district hospital, Mbozi district, southern Tanzania, in whom extensive NCC was confirmed by neuroimaging. CASE PRESENTATIONS: Patient 1 was a 55-year-old female from the tribe Malila smallholder farmer who has had four generalized tonic-clonic epileptic seizures over a period of 11 years and one episode of transient left hemiparesis one year before seizure onset. The patient also reported monthly to weekly episodes of severe, progressive, unilateral headache. The computed tomography (CT) scan of the brain showed 25 NCC lesions of which 15 were in the vesicular stage. Patient 2 was a 30-year-old male from tribe Nyha mechanic who reported monthly episodes of moderate to severe, progressive, bilateral headache, but no epileptic seizures. The CT scan showed 63 NCC lesions of which 50 were in the vesicular stage. Patient 3 was a 54-year-old female from the tribe Malila smallholder farmer who suffered from frequent generalized tonic-clonic epileptic seizures with potential signs of focal seizure onset. She also reported weekly to daily episodes of severe, progressive, unilateral headache. The CT scan showed 29 NCC lesions of which 28 were in the vesicular stage. CONCLUSIONS: Clinical presentation of NCC with multiple brain lesions varies considerably ranging from few epileptic seizures and severe headache to severe epilepsy with frequent epileptic seizures. Individuals with neurological signs/symptoms that may be due to NCC, based for example on epidemiological criteria or serological evidence of cysticercosis, are recommended to undergo neuroimaging before anthelminthic treatment is considered.

CSPG4 as a target for the specific killing of triple-negative breast cancer cells by a recombinant SNAP-tag-based antibody-auristatin F drug conjugate.

PURPOSE: Triple-negative breast cancer (TNBC) is phenotypic of breast tumors lacking expression of the estrogen receptor (ER), the progesterone receptor (PgR), and the human epidermal growth factor receptor 2 (HER2). The paucity of well-defined molecular targets in TNBC, coupled with the increasing burden of breast cancer-related mortality, emphasizes the need to develop targeted diagnostics and therapeutics. While antibody-drug conjugates (ADCs) have emerged as revolutionary tools in the selective delivery of drugs to malignant cells, their widespread clinical use has been hampered by traditional strategies which often give rise to heterogeneous mixtures of ADC products. METHODS: Utilizing SNAP-tag technology as a cutting-edge site-specific conjugation method, a chondroitin sulfate proteoglycan 4 (CSPG4)-targeting ADC was engineered, encompassing a single-chain antibody fragment (scFv) conjugated to auristatin F (AURIF) via a click chemistry strategy. RESULTS: After showcasing the self-labeling potential of the SNAP-tag component, surface binding and internalization of the fluorescently labeled product were demonstrated on CSPG4-positive TNBC cell lines through confocal microscopy and flow cytometry. The cell-killing ability of the novel AURIF-based recombinant ADC was illustrated by the induction of a 50% reduction in cell viability at nanomolar to micromolar concentrations on target cell lines. CONCLUSION: This research underscores the applicability of SNAP-tag in the unambiguous generation of homogeneous and pharmaceutically relevant immunoconjugates that could potentially be instrumental in the management of a daunting disease like TNBC.

Click Chemistry-Generated Auristatin F-Linker-Benzylguanine for a SNAP-Tag-Based Recombinant Antibody-Drug Conjugate Demonstrating Selective Cytotoxicity toward EGFR-Overexpressing Tumor Cells.

Antibody-drug conjugates (ADCs) are bifunctional molecules combining the targeting potential of monoclonal antibodies with the cancer-killing ability of cytotoxic drugs. This simple yet intelligently designed system directly addresses the lack of specificity encountered with conventional anti-cancer treatment regimes. However, despite their initial success, the generation of clinically sustainable and effective ADCs has been plagued by poor tumor penetration, undefined chemical linkages, unpredictable pharmacokinetic profiles, and heterogeneous mixtures of products. To this end, we generated a SNAP-tag-based fusion protein targeting the epidermal growth factor receptor (EGFR)-a biomarker of aggressive and drug-resistant cancers. Here, we demonstrate the use of a novel click coupling strategy to engineer a benzylguanine (BG)-linker-auristatin F (AuriF) piece that can be covalently tethered to the EGFR-targeting SNAP-tag-based fusion protein in an irreversible 1:1 stoichiometric reaction to form a homogeneous product. Furthermore, using these recombinant ADCs to target EGFR-overexpressing tumor cells, we provide a proof-of-principle for generating biologically active antimitotic therapeutic proteins capable of inducing cell death in a dose-dependent manner, thus alleviating some of the challenges of early ADC development.

Upper abdominal cytoreduction and thoracoscopy for advanced epithelial ovarian cancer: unanswered questions and the impact on treatment.

Gynaecological oncologists, by conducting Phase II and III chemotherapy trials, have sought to improve survival in women with epithelial ovarian cancer. The greatest impact on survival has been the use of intraperitoneal chemotherapy in women who have had all visible disease removed. No change in drug regimen has had an impact on survival equivalent to that associated with complete cytoreduction or the use of intraperitoneal chemotherapy. Interestingly, these two treatment modalities (complete cytoreduction and intraperitoneal chemotherapy) have not been universally adopted. Most often it is the inability to achieve optimal cytoreduction in the upper abdomen that defines the limit of the cytoreductive effort, and ultimately the integration of intraperitoneal chemotherapy. The importance of identifying disease outside the abdominal cavity, along with achieving complete cytoreduction, is paramount, if the use of intraperitoneal chemotherapy is to be logically integrated in treatment algorithms for women with advanced-stage epithelial ovarian cancer. This report summarises pertinent literature on upper abdominal cytoreduction, discusses surgical techniques and introduces new data on women with epithelial ovarian cancer undergoing thoracoscopy, suggesting consideration of its incorporation into the surgical management of advanced epithelial ovarian cancer.

Management of the abnormal Papanicolaou smear and colposcopy in pregnancy: an evidenced-based review.

Women diagnosed with abnormal Papanicolau smears or cervical abnormalities during pregnancy present a challenge to health care providers, as conventional management guidelines appropriate for the non-pregnant population may be contraindicated. The physiologic effects of pregnancy that may result in greater difficulty with the colposcopic examination include increased cervical mucus production that may obscure visualization, cervical hyperemia, gland prominence, and eversion of the columnar epithelium. The squamo-columnar junction may also be difficult to visualize in early pregnancy, but will often evert as the pregnancy continues. Because of these changes, cervical dysplasia may have a more prominent appearance in the gravid patient. Therefore, colposcopy should be performed by a skilled examiner with expertise in the cervical changes of pregnancy. The primary goal of colposcopy during pregnancy is to exclude the presence of invasive cancer, and thus, many cervical lesions may be followed with serial cytology and colposcopy during pregnancy or by deferring further colposcopic examination until the postpartum period. Cervical biopsy should be avoided unless a malignancy is suspected and endocervical sampling is contraindicated. Herein, we present a contemporary, evidence-based review of the colposcopic examination and guidelines for triaging and evaluating abnormal cervical cytology and lesions that are diagnosed during pregnancy.

Can COVID-19 pandemic worsen previous neurological/psychiatric diseases?

Introduction: The SARS-CoV-2 pandemic has been affecting the world since January 2020. Although its pathogenesis is primarily directed to the respiratory tract, other organs may be affected, including the nervous system. It has also been shown that the social context (confinement, lack of treatment) has affected neurological patients during this period. The aim of the study it was to assess the subjective worsening of neurological/psychiatric diseases in the context of the SARS-Cov-2 pandemic. Methods: Three groups of neurological/psychiatric patients were included: Patients who had symptomatic COVID-19 (n = 89), patients who had asymptomatic COVID-19 (n = 40), and a control group (n = 47), consisting of neurological/psychiatric patients without a history of SARS-Cov-2 infection. Results: 30.7% of the included individuals considered that their basal pathology had worsened during the study period. This feeling was significantly more frequent (P = 0.01) in patients with symptomatic COVID-19 (39.3%) than in patients of the other 2 groups (21.8%). Worsening was not related to the severity of COVID-19. The neurological conditions that significantly worsened after COVID-19, comparing symptomatic COVID-19 with the other 2 groups, were demyelinating and degenerative diseases. Conclusions: These results confirmed the impact of the SARS-Cov-2 pandemic on patients with neurological/psychiatric diseases. Confinement, lack of medical care, and the threat of diagnosis are surely contributing factors. Although the finding of a higher frequency of worsening in symptomatic COVID-19 patients may be related to greater anxiety/depression in this group of patients, we cannot exclude the role of direct affectation of the nervous system by the virus or damage due to neuroinflammation.

Introducción: La pandemia por SARS-CoV-2 afecta al mundo desde enero de 2020. Aunque su patogenia se dirige principalmente a las vías respiratorias, otros órganos pueden verse afectados, incluido el sistema nervioso. También se ha demostrado que el contexto social (confinamiento, falta de tratamiento) ha afectado a los pacientes neurológicos durante este periodo. El objetivo del estudio fue evaluar el empeoramiento subjetivo de enfermedades neurológicas/psiquiátricas en el contexto de la pandemia por SARS-Cov-2. Métodos: Se incluyeron tres grupos de pacientes neurológicos/psiquiátricos: pacientes que tenían COVID-19 sintomático (n = 89), pacientes que tenían COVID-19 asintomático (n = 40) y un grupo control (n = 47), formado por pacientes neurológicos/psiquiátricos sin antecedentes de infección por SARS-Cov-2. Resultados: El 30,7% de los individuos incluidos consideró que su patología basal había empeorado durante el período de estudio. Este sentimiento fue significativamente más frecuente (p = 0,01) en pacientes con COVID-19 sintomático (39,3%) que en pacientes de los otros 2 grupos (21,8%). El empeoramiento no estuvo relacionado con la gravedad de COVID-19. Las condiciones neurológicas que empeoraron significativamente después de la COVID-19, comparando la COVID-19 sintomática con los otros 2 grupos, fueron las enfermedades desmielinizantes y degenerativas. Conclusiones: estos resultados confirmaron el impacto de la pandemia del SARS-Cov-2 en pacientes con enfermedades neurológicas/psiquiátricas. El encierro, la falta de atención médica y la amenaza del diagnóstico son seguramente factores contribuyentes. Aunque el hallazgo de una mayor frecuencia de empeoramiento en pacientes sintomáticos de COVID-19 puede estar relacionado con una mayor ansiedad/depresión en este grupo de pacientes, no podemos excluir el papel de la afectación directa del sistema nervioso por el virus o el daño por neuroinflamación.

Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Racial disparities in surgical care for uterine cancer.

OBJECTIVE: To evaluate the association of race and surgical approach for women who underwent surgical treatment for uterine cancer. METHODS: The design was a retrospective cohort study of discharge data from nonfederal acute care hospitals in Maryland from 2000 to 2009. Women aged 18 and older who underwent hysterectomy for uterine cancer were included in the study population. The main outcome measure was receipt of lymphadenectomy. Secondary outcomes included receipt of minimally-invasive surgical approach, in-hospital mortality and individual surgeon and individual hospital annual uterine cancer case volume. The independent variable was race. We used logistic regression to calculate odds ratios and confidence intervals for each outcome of interest. Caucasians were the reference group. RESULTS: Among 5470 women who underwent hysterectomy, 2727 (49.9%) underwent lymphadenectomy and 512 (9.4%) underwent surgery through a minimally-invasive approach. After adjusting for age, payer status and APR-DRG mortality risk score, African-Americans were more likely to be operated on by high-volume surgeons (adjusted OR=1.27, 95% CI: 1.09-1.49) yet were less likely to undergo minimally-invasive surgery (adjusted OR=0.60, 95% CI: 0.45-0.80). For the outcome of lymphadenectomy, there was no significant difference between Caucasians and African-Americans (OR=1.13, 95% CI: 0.98-1.30). There was no association between race and in-hospital mortality or between race and the odds of undergoing surgery at a high-volume hospital. CONCLUSION: In this retrospective analysis of uterine cancer patients, race is associated with likelihood of undergoing surgery through a minimally-invasive approach. Further analysis using prospectively collected data with more detail regarding peri-operative parameters is needed to further clarify possible reasons for this disparity.

Antibody-Based Targeted Interventions for the Diagnosis and Treatment of Skin Cancers.

BACKGROUND: Cutaneous malignancies most commonly arise from skin epidermal cells. These cancers may rapidly progress from benign to a metastatic phase. Surgical resection represents the gold standard therapeutic treatment of non-metastatic skin cancer while chemo- and/or radiotherapy are often used against metastatic tumors. However, these therapeutic treatments are limited by the development of resistance and toxic side effects, resulting from the passive accumulation of cytotoxic drugs within healthy cells. OBJECTIVE: This review aims to elucidate how the use of monoclonal Antibodies (mAbs) targeting specific Tumor Associated Antigens (TAAs) is paving the way to improved treatment. These mAbs are used as therapeutic or diagnostic carriers that can specifically deliver cytotoxic molecules, fluorophores or radiolabels to cancer cells that overexpress specific target antigens. RESULTS: mAbs raised against TAAs are widely in use for e.g. differential diagnosis, prognosis and therapy of skin cancers. Antibody-Drug Conjugates (ADCs) particularly show remarkable potential. The safest ADCs reported to date use non-toxic photo-activatable Photosensitizers (PSs), allowing targeted Photodynamic Therapy (PDT) resulting in targeted delivery of PS into cancer cells and selective killing after light activation without harming the normal cell population. The use of near-infrared-emitting PSs enables both diagnostic and therapeutic applications upon light activation at the specific wavelengths. CONCLUSION: Antibody-based approaches are presenting an array of opportunities to complement and improve current methods employed for skin cancer diagnosis and treatment.

Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases. / Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Can a plantar pressure-based tongue-placed electrotactile biofeedback improve postural control under altered vestibular and neck proprioceptive conditions?

We investigated the effects of a plantar pressure-based tongue-placed electrotactile biofeedback on postural control during quiet standing under normal and altered vestibular and neck proprioceptive conditions. To achieve this goal, 14 young healthy adults were asked to stand upright as immobile as possible with their eyes closed in two Neutral and Extended head postures and two conditions of No-biofeedback and Biofeedback. The underlying principle of the biofeedback consisted of providing supplementary information related to foot sole pressure distribution through a wireless embedded tongue-placed tactile output device. Center of foot pressure (CoP) displacements were recorded using a plantar pressure data acquisition system. Results showed that (1) the Extended head posture yielded increased CoP displacements relative to the Neutral head posture in the No-biofeedback condition, with a greater effect along the anteroposterior than mediolateral axis, whereas (2) no significant difference between the two Neutral and Extended head postures was observed in the Biofeedback condition. The present findings suggested that the availability of the plantar pressure-based tongue-placed electrotactile biofeedback allowed the subjects to suppress the destabilizing effect induced by the disruption of vestibular and neck proprioceptive inputs associated with the head extended posture. These results are discussed according to the sensory re-weighting hypothesis, whereby the CNS would dynamically and selectively adjust the relative contributions of sensory inputs (i.e. the sensory weights) to maintain upright stance depending on the sensory contexts and the neuromuscular constraints acting on the subject.

Human and porcine neurocysticercosis: differences in the distribution and developmental stages of cysticerci.

OBJECTIVE: To describe and compare the clinical impacts of neurocysticercosis (NC) caused by Taenia solium in humans and pigs. METHODS: Comparative study of the brains of 16 asymptomatic pigs and 35 human NC cases (15 asymptomatic and 20 symptomatic). RESULTS: In humans, cysticerci were more frequently located in the ventricles and subarachnoid space at the base of the brain (11.8%vs. 1.6%; P = 0.001 and 25.9%vs. 0%; P < 0.0001, respectively) while in pigs, cysticerci were more frequently found in the parenchyma (44.4%vs. 7.6%; P < 0.0001). In human brains, 75.9% of the cysticerci were calcified, while in pigs all cysticerci were in the vesicular stage. CONCLUSION: The duration of infection and the host-parasite relationship (such as immune reactivity and brain haemodynamics) differ between humans and pigs. This may account for the different distribution and stage of the cysticerci among humans and pigs.

Parasite contamination of soil in households of a Mexican rural community endemic for neurocysticercosis.

High neurocysticercosis (NC) prevalence was recently determined by a computed tomography (CT) scan study in the community of Tepetzitzintla, State of Puebla, Mexico. The aim of the present work was to evaluate the magnitude of fecal and parasite contamination by Taenia spp. in the soil of households of this community during the four seasons of the year. The toilet, backyard, kitchen, washboard, water containers and corrals of 14 to 26 households were sampled during each season. High Taenia spp. egg intensity was found in 24.2% of the sampled areas. The highest percentage was detected in Spring and the lowest in Summer. Significantly higher levels of Taenia spp. eggs were present in kitchen soil samples. A significant correlation was found between the presence of Taenia spp. eggs in household soil during the Summer, and NC diagnoses of the inhabitants by CT scan. Coproparasitological examinations and anti-cysticercal antibodies were determined in a cohort of inhabitants of the sampled households. Antibody levels and coproparasitological results were not associated with NC. Overall, these results illustrate the high degree of fecal contamination of potential risk to human health in rural communities and could be of use for control programmes.

Preferential growth of Taenia crassiceps cysticerci in female mice holds across several laboratory mice strains and parasite lines.

A retrospective study of our 14-yr records on experimental Taenia crassiceps (ORF(fast) line) cysticercosis (n = 1,198) shows that in 16 of 17 different mice strains, female mice are more frequently infected and carry larger individual parasite loads than males. However, sexual differences in parasite loads significantly varies between strains in relation to their different genetic backgrounds (BALB > C57Bl = OTHERS > C3H). The coefficient of variation in all female mice is significantly smaller than that of all males, an indication of males' more potent, but erratically effective, restraint of cysticercus growth. Similar positive growth bias for female mice is shown by other lines of cysticerci, i.e., HYG(slow) and WFU(slow). These results contravene the usual expectation of female hosts being more resistant than males to parasite infections, and they point to the multiple factors that combined determine sex related differences of mice to experimental cysticercosis infection.