Sciatic Neuropathy: Case Report and Discussion of the Literature on Postoperative Sciatic Neuropathy and Sciatic Nerve Tumors

Sciatic nerve injury and dysfunction is not an uncommon cause of lower extremity symptoms in a musculoskeletal practice. We present the case of a man who presented with lower extremity weakness, pain, and cramps, and was initially diagnosed at an outside institution with bilateral S1 radiculopathies and recommended for spine surgery. He came to us for a second opinion. Electrodiagnostic testing revealed an isolated sciatic neuropathy and the patient was referred for imaging, which showed a sciatic nerve sheath tumor. Review of the literature on sciatic neuropathies shows that there can be many possible etiologies of sciatic nerve dysfunction, but that hip arthroplasty continues to be the leading risk factor. Sciatic nerve tumors are not commonly described in the literature and their definitive management remains unclear.     

School nurses' support for bereaved students: a pilot study.

Children may have difficulty with schoolwork because of grief over the death of an important person in their lives. School nurses provide support to these children. This pilot study consisted of a Web-based survey completed by 6 school nurses in a 3-county area in Washington state. The purpose of this pilot study was to assess the need for additional support for bereaved children and the extent to which school nurses meet the needs of these students. Results indicated that many school nurses have large caseloads that preclude spending as much time with bereaved students as the nurses feel is necessary. Bereaved students exhibit a wide variety of grief symptoms that may interfere with learning. In addition, rural areas do not have adequate community bereavement resources that nurses can use to refer students who need help beyond that offered at school. Nurses must be more active in supporting students within the school setting despite limited resources.     

Inverted terminal repeat sequences of adeno-associated virus enhance the antibody and CD8(+) responses to a HIV-1 p55Gag/LAMP DNA vaccine chimera

The immune responses to an HIV-1 p55Gag vaccine encoded as a DNA chimera with the lysosomal associated membrane protein-1 (LAMP) have been examined for the effect of the addition of the inverted terminal repeat (ITR) sequences of the adeno-associated virus (AAV) to the DNA plasmid construct, and of packaging the LAMP/gag gene as a recombinant AAV vector (rAAV). DNA plasmids encoding Gag and the LAMP/Gag protein chimera were constructed in two vectors, the pcDNA3.1 and a corresponding plasmid containing the ITR sequences (pITR) flanking the expression elements of the plasmid, and the pITR LAMP/gag DNA plasmid was encapsidated in the rAAV vector. Human 293 cells transfected in vitro with LAMP/gag plasmids either in pcDNA3.1 or pITR produced much Gag protein in cell extracts (1.6 and 2.2 ng of Gag/mg of protein, respectively). The immune responses of mice to immunization with these constructs were examined under three protocols: DNA prime/DNA boost, DNA prime/rAAV boost, and a single rAAV immunization. The results demonstrated that under DNA prime/DNA boost protocol, the "naked" DNA vaccines encoding the LAMP/gag chimera, either as pcDNA3.1 or pITR DNA plasmid constructs, elicited strong CD4(+) T cell responses. In contrast, significantly higher levels of CD8(+) and antibody responses were observed with the pITR-DNA constructs. Immunization with the rAAV vector under the DNA prime/rAAV boost protocol resulted in sustained T cell responses and a markedly increased antibody response, predominantly of the IgG(1) isotype resulting from the activation of the Th2 subset of CD4(+) T cells, that was sustained for at least 5 months after immunization.     

Novel twelve-generation kindred of fatal familial insomnia from germany representing the entire spectrum of disease expression

We present a novel large German kindred of fatal familial insomnia (FFI) consisting of three branches and comprising more than 800 individuals of 12 generations, the largest pedigree of any familial prion disease known today. There is a wide spectrum of clinical presentations leading to misdiagnoses of Olivo-Ponto-Cerebellar Atrophy (OPCA), Parkinson's or Alzheimer's disease in addition to Creutzfeldt-Jakob disease (CJD) and Gerstmann-Str?ussler-Scheinker (GSS) syndrome. Molecular genetic analysis of the prion protein gene (PRNP) confirmed the mutation D178N segregating with methionine at the polymorphic codon 129 of PRNP in all 7 patients examined. This polymorphism at codon 129 is supposed to discriminate between familial CJD (fCJD) and FFI; the 129M allele determines FFI and 129V fCJD. Furthermore, heterozygosity at this site appears to induce prolonged disease duration as compared to the homozygous condition. The variability of the clinical and pathological findings documented for our patients indicates the difficulty in establishing the diagnosis of FFI on clinical and on pathological grounds alone. In three cases (IX-97, XI-21, V-2) followed up by us prospectively insomnia was an early and severe symptom; however, in case notes analyzed retrospectively this symptom was frequently missed. In contrast to previous reports and in agreement with recent studies we cannot confirm a clear relationship between the status of the M/V polymorphism at codon 129 and the age-of-onset of this disease.     

Immune regulation during allergic bronchopulmonary mycosis

Allergic bronchopulmonary mycosis (ABPM) is a devastating pulmonary disease that results from an aggressive allergic response to fungal colonization in the airways. Animal models using either fungal antigen or live infection reproduce most of the clinical features seen during ABPM in humans. Results from these studies have facilitated a detailed analysis of the key factors involved in the afferent as well as efferent phase of the disease. This review focuses on allergic bronchopulmonary disease caused by two different fungi (Aspergillus fumigatus and Cryptococcus neoformans): allergic bronchopulmonary aspergillosis and allergic bronchopulmonary cryptococcosis. Observations from both models underline the importance of initial innate immune responses and their translation into appropriate adaptive responses. In addition, data derived from knockout studies give emphasis to targeting cytokines and chemokines as a therapeutic strategy in the treatment of ABPM.     

Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F,EA- 2R) along with Epstein–Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis

Introduction:Worldwide, breast cancer (BC) is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world’s population. Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India. Methodology:In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)– EBV PCR and Epstein–Barr virus latent membrane protein 1 (LMP1) IHC. Results:Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection. Conclusion:The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.Key Words: EBV, breast cancer, clinico-pathological variables, LMP1, viral oncogenesis     

Mesenteric panniculitis does not confer an increased risk for cancers: A systematic review and meta-analysis

Background:Mesenteric panniculitis (MP) is a non-specific, localized inflammation at the mesentery of small intestines which often gets detected on computed tomography. An association with malignant neoplasms remains unclear. We performed a systematic review and meta-analysis to examine the association of malignancy with MP.Methods:MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for articles published from inception to 2020 that evaluated the association of malignant neoplasms with MP in comparison with control groups. Using random-effects method, a summary odds ratio (OR) estimate with 95% confidence intervals for malignant neoplasms in MP was estimated.Results:Four case-control studies reporting data on 415 MP patients against 1132 matched-controls met inclusion criteria and were analyzed. The pooled OR for finding a malignant neoplasm in patients with MP was 0.907 (95% CI: 0.688–1.196; P = .489). The heterogeneity was mild and non-significant. Also, there was no heightened risk of any specific type of malignancy with MP. Three more case-series with unmatched-control groups (MP: 282, unmatched-controls: 17,691) were included in a separate analysis where the pooled OR of finding a malignant neoplasm was 2.963 (95% CI: 1.434–6.121; P = .003). There was substantial heterogeneity in this group.Conclusion:This meta-analysis of matched controlled studies proves absence of any significant association of malignant neoplasms with MP. Our study also demonstrates that the putative association of malignancy with MP is mainly driven by uncontrolled studies or case-series.     

Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.     

Singlet oxygen-mediated synthesis of malarial chemotherapeutic agents

Malaria is the leading infectious disease found in humans, affecting third-world countries. Worldwide, more than two billion people are at risk of malaria, with about 500 million clinical cases of malaria each year and one million deaths. In this focused review, an effort has been made to summarize the reactions of singlet oxygen with organic substrates, their stereoselectivity, stereospecificity and utilization in generating dioxetanes and endoperoxides. The study of production and reactivity indications of this exceptional molecule has emerged as a rich and diverse area in the synthesis of antimalarials like artemisinin and its semisynthetic derivatives, structurally simple 1,2,4-trioxanes, sesquiterpene isonitriles, synthetic cyclic, and other acyclic peroxides. Artermisinin, a mainstay in antimalarial drug therapy, meets the dual challenge posed by drug-resistant parasites and rapid advancement of lethal malarial threat. The cardinal mechanism of peroxidation and ring closure in its production are induced by singlet oxygen and acid. Moreover, its complex structure restricts the complete chemical synthesis of artemisinin. Consequently, the limited availability coupled with increasing demand for artemisinin has paved the way for the preparation of synthetic alternatives of artemisinin and its derivatives. Likewise, past evidence of the structure–activity relationship indicate the importance of singlet oxygen in antimalarial drug synthesis. It is anticipated that this compendium on the chemistry of singlet oxygen will be of use to organic/medicinal chemists and pharmacologists working on antimalarial drug development.