Survival patterns in treated cases of carcinoma larynx in North India: A 10-year follow-up study

Carcinoma of larynx is a common disease in North Indian population. It is seen commonly in smokers and alcoholics. It poses a serious health problem due to its tendency to cause airway obstruction and to make the patient aphonic if total larynxgectomy is done for curing this cancer. We conducted a retrospective analysis in 690 cases of carcinoma larynx presenting to Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh. Various aspects of this disease like predisposing factors, patterns of spread, histological types, various treatment modalities, their complications and response of this disease to these therapeutic options were studied in detail.     

Pure Sertoli cell tumor of the ovary: A case report

Pure Sertoli cell tumors are an uncommon variant of rare ovarian Sertoli‐Leydig cell tumors. Due to nonspecific clinical and imaging features, diagnosis is often made after histopathological examination. The prognosis is excellent as most are detected in the early stages and surgical resection is often curative in most cases.     

Psychosocial Correlates of Monocyte Activation and HIV Persistence in Methamphetamine Users

This cross-sectional study investigated the associations of psychosocial factors relevant to recovery from substance use disorders with monocyte activation and HIV persistence in a sample of 84 HIV-positive, methamphetamine-using sexual minority men with undetectable HIV viral load (<40 copies/mL). We examined if psychosocial factors were associated with decreased soluble CD14 (sCD14) and lower proviral HIV DNA. Multiple linear regression models adjusted for age, anti-retroviral therapy regimen, and CD4+ T-cell count. Time on ART was also included in models examining proviral HIV DNA. Greater self-efficacy for managing methamphetamine triggers and higher social support for abstinence were independently associated with lower sCD14. Greater social support for abstinence was also independently associated with lower proviral HIV DNA. Psychosocial factors relevant to recovery from substance use disorders are associated with lower monocyte activation and decreased proviral HIV DNA. Findings underscore the need for longitudinal research to identify plausible mechanisms linking psychosocial factors and substance use with biological processes relevant to HIV pathogenesis.

     

Overview for various aspects of the health benefits of Piper longum linn. fruit

Herbal remedies have become popular, due in part to the lower risk of adverse reactions. Thousands of plants have been used traditionally to treat various diseases. Among them, species of the genus Piper are important medicinal plants used in various systems of medicine. The Piper longum fruit has been used in traditional medicine, including the Ayurvedic system of medicine. Although there are numerous indications for its use, controlled trials are needed to determine its efficacy. The primary constituents isolated from various parts of P. longum are piperine, piperlongumine, sylvatin, sesamin, diaeudesmin piperlonguminine, pipermonaline, and piperundecalidine. It is most commonly used to treat chronic bronchitis, asthma, constipation, gonorrhea, paralysis of the tongue, diarrhea, cholera, chronic malaria, viral hepatitis, respiratory infections, stomachache, bronchitis, diseases of the spleen, cough, and tumors. This study provides detailed information about the P. longum fruit, including phytochemistry, pharmacological profile and safety profile. In view of the commercial, economic, and medicinal importance of the P. longum plant, it is useful for researchers to study the plant in detail.     

Bispecific MAb aided liposomal drug delivery

We have developed a new method for specifically delivering liposomal model drugs to tumor cells. Bispecific monoclonal antibodies (bsMAb) (174H.64 x anti-biotin) which can bind tumor-specific antigen and biotin were developed and characterized. Biotinylated stealth liposome loaded with model drug 99mTc-DTPA can bind to the biotin-binding arm of bsMAb. This targeted liposomal delivery strategy was tested in mouse KLN-205 squamous carcinoma model. bsMAbs were administered 24h in advance into tumor allograft bearing mice, which allow them to bind to tumor cells through the anti-tumor binding arm. After clearance of circulating bsMAb, biotinylated stealth liposomes were introduced to specifically bind to the tumor sites where bsMAb localized earlier. The results show that pretargeted bsMAb can enhance liposomal drug targeting by four times, 3.61% dose/g vs. 0.89% dose/g. This bsMAb/liposome strategy show the broad possibilities of selective delivery of cytotoxic drugs or genes to the specific targets.     

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.     

Nanomagnet-facilitated pharmaco-compatibility for cancer diagnostics: Underlying risks and the emergence of ultrasmall nanomagnets

Cancer therapy is a fast-emerging biomedical paradigm that elevates the diagnostic and therapeutic potential of a nanovector for identification, monitoring, targeting, and post-treatment response analysis. Nanovectors of superparamagnetic iron oxide nanoparticles (SPION) are of tremendous significance in cancer therapy because of their inherited high surface area, high reactivity, biocompatibility, superior contrast, and magnetic and photo-inducibility properties. In addition to a brief introduction, we summarize various progressive aspects of nanomagnets pertaining to their production with an emphasis on sustainable biomimetic approaches. Post-synthesis particulate and surface alterations in terms of pharmaco-affinity, liquid accessibility, and biocompatibility to facilitate cancer therapy are highlighted. SPION parameters including particle contrast, core-fusions, surface area, reactivity, photosensitivity, photodynamics, and photothermal properties, which facilitate diverse cancer diagnostics, are discussed. We also elaborate on the concept of magnetism to selectively focus chemotherapeutics on tumors, cell sorting, purification of bioentities, and elimination of toxins. Finally, while addressing the toxicity of nanomaterials, the advent of ultrasmall nanomagnets as a healthier alternative with superior properties and compatible cellular interactions is reviewed. In summary, these discussions spotlight the versatility and integration of multi-tasking nanomagnets and ultrasmall nanomagnets for diverse cancer theragnostics.     

Retinal detachment in eyes treated with Aurolab aqueous drainage implant for refractory glaucoma - Incidence and outcomes

Purpose:To analyze the incidence of rhegmatogenous retinal detachment (RRD) in patients who have undergone prior Aurolab aqueous drainage implant (AADI) surgery and report outcomes in terms of anatomic, visual acuity, and intraocular pressure (IOP) findings.Methods:Case records of all patients who underwent RRD repair after AADI surgery from 2013 to 2019 were retrospectively analyzed. Data collected included patient demographics, ocular examination findings at all visits including IOP and best-corrected visual acuity (BCVA) and clinical findings related to RRD both at baseline and postoperatively.Results:Ten eyes of nine patients were included in study. The mean age of patients was 28.2 years (median: 15 years, range: 6–83 years). Mean duration between AADI and RRD was 14 months (median 2.5 months; range 2 days-72 months). All eyes underwent pars plana vitrectomy with silicon oil injection. The preoperative LogMAR BCVA (logarithm of the minimum angle of resolution) was 2.52 ± 0.15 which improved to 2.29 ± 0.58 at final follow-up; however, only one eye had vision ≥ 20/400 largely due to recurrent RRD and advanced glaucomatous disc damage. Postoperatively retina was attached in 6 eyes (60%) and IOP was ≤ 21 mmHg in 5 out of 6 eyes with anatomic successConclusion:The incidence of RRD following AADI was found to be 0.86% in our study. Pars plana vitrectomy (PPV) with silicon oil tamponade was the preferred approach in the management of these eyes with IOP being well controlled post PPV. However, visual acuity outcomes were largely unsatisfactory due to recurrent RRD and preexisting advanced glaucoma.     

Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants

The first-generation COVID-19 vaccines have been effective in mitigating severe illness and hospitalization, but recurring waves of infections are associated with the emergence of SARS-CoV-2 variants that display progressive abilities to evade antibodies, leading to diminished vaccine effectiveness. The lack of clarity on the extent to which vaccine-elicited mucosal or systemic memory T cells protect against such antibody-evasive SARS-CoV-2 variants remains a critical knowledge gap in our quest for broadly protective vaccines. Using adjuvanted spike protein–based vaccines that elicit potent T cell responses, we assessed whether systemic or lung-resident CD4 and CD8 T cells protected against SARS-CoV-2 variants in the presence or absence of virus-neutralizing antibodies. We found that 1) mucosal or parenteral immunization led to effective viral control and protected against lung pathology with or without neutralizing antibodies, 2) protection afforded by mucosal memory CD8 T cells was largely redundant in the presence of antibodies that effectively neutralized the challenge virus, and 3) “unhelped” mucosal memory CD8 T cells provided no protection against the homologous SARS-CoV-2 without CD4 T cells and neutralizing antibodies. Significantly, however, in the absence of detectable virus-neutralizing antibodies, systemic or lung-resident memory CD4 and “helped” CD8 T cells provided effective protection against the relatively antibody-resistant B1.351 (β) variant, without lung immunopathology. Thus, induction of systemic and mucosal memory T cells directed against conserved epitopes might be an effective strategy to protect against SARS-CoV-2 variants that evade neutralizing antibodies. Mechanistic insights from this work have significant implications in the development of T cell–targeted immunomodulation or broadly protective SARS-CoV-2 vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to exert devastating impacts on the human life, with >280 million infections and over 5.4 million deaths to date. Although there are millions of convalescent people with some measure of immunity and 8.8 billion doses of vaccine administered to date, further threats of widespread severe COVID-19 disease looms heavily as immunity induced by infection or the first-generation vaccines may not provide effective and durable protection, either due to waning immunity or due to poor antibody cross-reactivity to new variants (1–5).It is clear that virus-neutralizing antibodies provide the most effective protection to SARS-CoV-2, following vaccination or recovery from infection (6). However, T cell–based protection against SARS-CoV-2 has become a central focus because T cells recognize short amino acid sequences that can be conserved across viral variants (7–9). Indeed, T cells in convalescent COVID-19 patients have shown robust responses that are directed at multiple viral proteins, and depletion of these T cells delayed SARS-CoV-2 control in mice (10–12). These data suggest a protective role for T cells in COVID-19 infection. In effect, what constitutes an effective, an ineffective, or a perilous T cell response to SARS-CoV-2 in lungs remains poorly defined. Controlled studies in laboratory animals are of critical importance to elucidate the role and nature of T cells in lungs during SARS-CoV-2 virus infection and in protective immunity.Based on the differentiation state, anatomical localization and traffic patterns, memory T cells are classified into effector memory (T_EM), central memory (T_CM), and tissue-resident memory (T_RM) (13, 14). There is accumulating evidence that airway/lung-resident T_RMs, and not migratory memory T cells (T_EMs) are critical for protective immunity to respiratory mucosal infections with viruses, such as influenza A virus (IAV) and respiratory syncytial virus (15–21). Development of T_RMs from effector T cells in the respiratory tract requires local antigen recognition and exposure to critical factors, such as transforming growth factor (TGF)-β and interleukin (IL)-15 (15). Therefore, mucosal vaccines are more likely to elicit T_RMs in lungs than parenteral vaccines (22, 23). A subset of effector T cells in airways of COVID-19 patients display T_RM-like features (24), but the development of T_RMs or their importance in protective immunity to reinfection are yet to be determined. Furthermore, all SARS-CoV-2 vaccines in use are administered parenterally and less likely to induce lung T_RMs. While depletion of CD8 T cells compromised protection against COVID-19 in vaccinated rhesus macaques (25), the relative effectiveness of vaccine-induced systemic/migratory CD8 T cell memory vs. lung/airway T_RMs in protective immunity to COVID-19 is yet to be defined.In this study, using the K18-hACE2 transgenic (tg) mouse model of SARS-CoV-2 infection, we have interrogated two key aspects of T cell immunity: 1) the requirements for lung-resident vs. migratory T cell memory in vaccine-induced immunity to SARS-CoV-2; and 2) the role of lung-resident memory CD4 vs. CD8 T cells in protection against viral variants in the presence or absence of virus-neutralizing antibodies. Studies of mucosal versus systemic T cell–based vaccine immunity using a subunit protein-based adjuvant system that elicits neutralizing antibodies and T cell immunity, demonstrated that: 1) both mucosal and parenteral vaccinations provide effective immunity to SARS-CoV-2 variants; 2) CD4 T cell–dependent immune mechanisms exert primacy in protection against homologous SARS-CoV-2 strain; and 3) the development of spike (S) protein-specific “unhelped” memory CD8 T cells in the respiratory mucosa are insufficient to protect against a lethal challenge with the homologous Washington (WA) strain of SARS-CoV-2. Unexpectedly, we found that systemic or mucosal lung-resident memory CD4 and “helped” CD8 T cells engendered effective immunity to the South African B1.351 β-variant in the apparent absence of detectable mucosal or circulating virus-neutralizing antibodies. Taken together, mechanistic insights from this study have advanced our understanding of viral pathogenesis and might drive rational development of next-generation broadly protective SARS-CoV-2 vaccines that induce humoral and T cell memory.