Diagnostic evaluation of nested PCR and microscopy for Cryptosporidiosis in goats: can COWP gene based qRT-PCR be useful in assessment of active Cryptosporidial infections?

The present research delved into the transmission patterns, diagnostic methods, molecular traits, and phylogenetic analysis of Cryptosporidium species. The research was undertaken to enhance comprehension of the epidemiology and the potential for zoonotic transmission. A total of 80 goat-kid samples were tested, 7 were confirmed positive by mZN microscopy and 12 by nested-PCR. By PCR, 18SSUrRNA, HSP70, and GP60 amplicons were tested for Cryptosporidium. The restriction enzymes viz., SspI, VspI and MboII were used to genotype 12 Cryptosporidium positive samples by which C. parvum and C. bovis mixed infections were detected. Quantitative reverse transcription real-time PCR was used to transcriptionally screen the COWP-subunit genes to assess the severity of the infection in goat-kids, which showed upregulation of COWP6 and COWP4, while COWP9 and COWP3 genes were downregulated. A silent mutation was found at the codon CCA→CCC, which is being reported for the first time in goat field isolates. Phylogenetic and sequencing analyses confirmed the presence of the anthropozoonotic IIe subtype.

Utilization of Smartphones and Attitude Regarding Their Use at the Workplace by Nurses: A Cross-Sectional Study.

INTRODUCTION: The use of personal smartphones in healthcare settings is widespread, with nurses often integrating these devices into their profession's practices. This study addresses the utilization of and attitudes toward smartphone use among nurses in the workplace. METHODS: This study uses a descriptive cross-sectional design and includes 258 nurses from various departments in a tertiary care teaching and research hospital in India. Data was collected using Google Forms (Google LLC, Mountain View, California, United States) through a socio-demographic questionnaire and two scales: "Utilization of Smartphones at Workplace" and "Attitude Regarding Smartphone Use at Workplace." RESULTS:  The findings indicate that a significant proportion (64.3%) of participants use their smartphones for less than an hour at the workplace. Notably, a substantial majority (78.7%) agree that employers should implement a policy regarding smartphone use. Additionally, 34.1% use their smartphones for personal reasons for less than an hour, with 24.4% specifically engaging in social media use with a statistically significant difference (p <0.05). CONCLUSION: The study finds an enormous gap in nurses' smartphone use, with a greater emphasis on personal and social media activities than professional responsibilities. Establishing a collaborative regulatory framework is essential for aligning smartphone use with patient care obligations and ensuring a balance between possible benefits and risks.

Modified FOLFIRINOX (mFOLFIRINOX) as neoadjuvant therapy and 'salvage' in patients with high risk locally advanced rectal cancers - tolerance and early outcomes.

BACKGROUND: There is limited data with regard to the use of modified 5-fluoroural-leucovorin-irinotecan-oxaliplatin (mFOLFIRINOX) in terms of tolerance and enabling total mesorectal excision (TME) of locally advanced rectal adenocarcinomas (LARC) with high-risk characteristics (T4b status, signet ring histology etc) post standard neoadjuvant long course chemoradiation (NACTRT) or short course radiation (SCRT) and chemotherapy. MATERIALS AND METHODS: Patients with LARC from January 2018 to December 2020 receiving mFOLFIRINOX post NACTRT/SCRT to facilitate TME were evaluated. The primary endpoint was assessment of grade 3 and grade 4 treatment related toxicity and TME rates. Event free survival (EFS), where event was defined as disease progression or recurrence post resection after mFOLFIRINOX, was calculated by Kaplan Meier method. RESULTS: Forty-seven patients were evaluated with a median age of 33 years (Range:18-59), 45% T4b status, 96% radiological circumferential margin (CRM) involved (79% CRM positive post NACTRT/SCRT), 43% extramural venous invasion (n=33) and 36% signet ring histology. 62% had received prior NACTRT and 38% had received SCRT with chemotherapy before receiving mFOLFIRINOX. The most common grade 3 and grade 4 treatment related side effects included diarrhoea (7%), anaemia (4%) and infections (4%). Intended duration of mFOLFIRINOX or beyond was completed in 94% of patients. 60% of patients underwent curative local resection with R0 resection rates of 100% (n=28) and pathological complete response rates of 21%. The most common surgeries done were exenterations and abdominoperineal in 22% and 17% patients respectively. With a median follow up of 19 months, 24 patients had recurred or progressed for a median EFS of 20 months [95% confidence interval (CI): 15-24]. CONCLUSIONS: Locally advanced rectal cancers with high-risk characteristics are a niche group of cancers with less-than-optimal outcomes post standard neoadjuvant strategies. mFOLFIRINOX appears to be well tolerated and enables TME in a significant proportion of these patients.

Non-operative management in low-lying rectal cancers undergoing chemoradiation.

PURPOSE: To evaluate the outcomes of post-neoadjuvant chemoradiation (NACTRT) wait-and-watch Strategy (WWS) in distal rectal cancers. MATERIALS AND METHODS: All consecutive patients from December 2012 to 2019 diagnosed with distal rectal tumors (T2-T4 N0-N+) having a complete or near-complete response (cCR or nCR, respectively) post-NACTRT and wishing for the non-surgical treatment option of WWS were included in this study. Patients were observed with 3 monthly magnetic resonance imaging (MRIs), sigmoidoscopies, and digital rectal examination for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), non-regrowth recurrence-free survival (NR-RFS) and overall survival (OAS) were estimated using the Kaplan-Meier method, and factors associated with LRR were identified on univariate and multivariate analysis using the log-rank test (P < 0.05 significant). RESULTS: Sixty-one consecutive patients post-NACTRT achieving cCR[44 (72%)] and nCR[17 (28%)], respectively, were identified. All patients received pelvic radiotherapy at a dose of 45-50Gy conventional fractionation and concurrent capecitabine. An additional boost dose with either an external beam or brachytherapy was given to 39 patients. At a median follow-up of 39 months, 11 (18%) patients had local regrowth, of which seven were salvaged with surgery and the rest are alive with the disease, as they refused surgery. The overall OPR, NR-RFS, and OS were 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastatectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). CONCLUSION: The WWS is a safe non-operative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.

Status of Identification of Communication Disorder in Children in Current Scenario: A Survey from West Bengal.

To find the status of age of suspicion and identification availed for children with different communication disorders. This cross-sectional survey study was conducted on 2081 children aged 0.5 to 15 years (mean: 5.41; S.D.: ±3.77) who came to the speech-language diagnostic department of AYJNISHD(D), RC, Kolkata for availing rehabilitation service at the institute. The information was gathered from the parents and caregivers of the children. After detailed evaluation by the interdisciplinary team, the developed 14-item questionnaire was administered, and data were recorded and tabulated. Findings suggested that average age of suspicion of presence of communication problem is 2 years (SD: ±0.98). The suspicion rate increased with increasing age with a saturation in suspicion rate after 5 years. Consultation of a medical professional, primarily an ENT specialist was availed by 2.8 years (SD: ±1.89) of age and 32% of the doctors during the first visit assured the parents not to worry as the child would learn language with age and only 43.4% were referred for rehabilitation. Among them, 42.8% of children were found hearing loss, 24.5% found to have autism spectrum disorder, 20.66% of children were diagnosed with developmental delay, 6.4% were diagnosed with intellectual disability, 4.7% were diagnosed with late language emergence and 0.86% were diagnosed with cerebral palsy. From the findings we can conclude perceived cause of delay in identification is lack of awareness, lack of proper guidance from the primary consultants, and tendency to follow wait-and-watch policy.

Frequency-tuned selectivity enhancement of Mg@ZnO-TiO2 nanoflake-based heterojunction sensor devices.

Selectivity improvement by the frequency tuning of Mg@ZnO-TiO2 nanoflake-based heterojunction devices under exposure to different volatile organic compounds is the prime focus of the present paper. The synthesis of Mg@ZnO-TiO2 nanoflakes was carried out using a solution process followed by a low-cost hydrothermal method. A capacitive measurement approach was used to find the resonant frequencies of the device in 2-butanone, acetone, 2-propanol, ethanol, and methanol environments in the frequency range from 0.001 to 220 kHz. A Cole-Cole plot derived from impedance measurements suggested that the device impedance consisted of capacitance (Cz = 2.01 pF and CT = 2.17 pF) and resistance (Rz = 13 552.2 kΩ and RT = 3500.574 kΩ) from the ZnO nanoflake layer and TiO2 thin film layer, respectively. The maximum capacitive responses to 2-butanone (C4H8O), acetone (C3H6O), 2-propanol (C3H8O), ethanol (C2H5OH), and methanol (CH3OH) were recorded at resonant frequencies of 1.000 kHz, 0.791 kHz, 0.702 kHz, 0.319 kHz and 0.103 kHz, respectively, at the corresponding temperature of 125 °C, 100 °C, 100 °C, 75 °C, and 75 °C, respectively. The device offered optimum capacitive responses of 221.32%, 242.65%, 317.09%, 373.96%, and 401.24% to 100 ppm of 2-butanone, acetone, 2-propanol, ethanol, and methanol, respectively. Experimental observation confirmed that the capacitive response inversely varied with the resonant frequency. Such an inverse relation was correlated with the dielectric variation at the junction interface, change in the molecular weights of VOCs, and their sticking coefficient. An equivalent circuit diagram with the help of adsorption-desorption isotherms and an energy band model is illustrated to correlate the device optimum capacitive response at the tuned frequencies under different VOC media.

Salmonella enterica serovars linked with poultry in India: antibiotic resistance profiles and carriage of virulence genes.

Salmonella is an important poultry pathogen with zoonotic potential. Being a foodborne pathogen, Salmonella-contaminated poultry products can act as the major source of infection in humans. In India, limited studies have addressed the diversity of Salmonella strains of poultry origin. This study represented 26 strains belonging to Salmonella serovars Typhimurium, Infantis, Virchow, Kentucky, and Agona. The strains were tested for resistance to 14 different antimicrobial agents using the Kirby-Bauer disk-diffusion assay. The presence of the invA, hilA, agfA, lpfA, sopE, and spvC virulence genes was assessed by polymerase chain reaction (PCR), and the genetic diversity was assessed by Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR). The highest resistance to tetracycline (n = 17; 65.38%) followed by nalidixic acid (n = 16; 61.53%) was detected among the strains. Among the strains (n = 17) phenotypically resistant to tetracycline, 94% (n = 16) were also positive for the tetA gene. Based on the presence of virulence genes, the strains were characterized into three virulence profiles (PI, P2, and P3). Among the investigated virulence genes, invA, hilA, agfA, and lpfA were present in all strains. The sopE gene was mostly associated with serovars Virchow (n = 3; 100%) and Typhimurium (n = 8; 80%), whereas spvC gene was exclusive for two Typhimurium strains that lacked sopE gene. ERIC-PCR profiling indicated clusters correlating their serovar, geographical, and farm origins. These results demonstrate that Salmonella isolates with a wide genetic range, antibiotic resistance, and virulence characteristics can colonize poultry. The presence of such strains is crucial for both food safety and public health.

Clinicohistoradiological and surgical outcome in diffuse midline glioma.

PURPOSE: Diffuse Midline Glioma (DMG) with H3K27M mutation is a rare and aggressive midline high grade glioma with a predominant astrocytic differentiation and K27M mutation in either H3F3A or HIST1H3B/C. This tumor is more common in children than in adults. The current study was aimed to determine clinicohistoradiological and surgical outcome of patients who have undergone surgery for DMG and study disease severity of patients with DMG. METHODS: This is an observational study in which 29 DMG patients were evaluated for clinicohistoradiological and surgical outcomes by assessing the pre and postoperative neurological status. RESULT: Survival duration was significantly high in patients with age > 18 years (p = 0.02). Patients who had undergone Radiation Therapy showed higher survival rate (p = 0.05) and the cases with low levels of Ki 67 index had improved post operative outcome (p = 0.002). CONCLUSION: DMG with H3K27M mutation in newly classified Central Nervous System tumor are WHO grade IV Tumors, comprising H3K27M mutation as molecular marker for diagnosis and related with a poor prognosis.

Assessment of genetic diversity of Trypanosoma evansi in the domestic animal populations through ITS-1 gene sequence analysis.

Trypanosoma evansi infects domestic animals, causing a debilitating and occasionally fatal disease. The disease leads to significant economic losses to farmers and poses a substantial impediment to the growth of livestock production in developing nations, including India. Considering the challenges associated with managing this infection, there is an urgent need to enhance our understanding of the molecular and genetic diversity of T. evansi. Therefore, this study was planned to analyze the genetic diversity of T. evansi using available internal transcribed spacer-1 (ITS-1) gene sequences from India and compare them with sequences from around the globe. Blood samples used in this study were collected from naturally infected animals including dogs, cattle, and buffaloes in the Indian state of Madhya Pradesh. Using the ITS-1 gene, we amplified a 540 base pairs (bp) segment using polymerase chain reaction (PCR), sequenced it, and identified intra-specific variations. Phylogenetic analysis of 90 sequences, including 27 from India, revealed three distinct clusters with high bootstrap support values. A haplotype network analysis identified 34 haplotypes, with H7 being the most prevalent, indicating a complex evolutionary history involving multiple countries. The genetic analysis of the Indian population revealed distinct characteristics. Despite low nucleotide diversity, there was high haplotype diversity in comparison to other populations. Tajima's D, Fu and Li's D, and Fu and Li's F exhibited non-significant negative values, indicating potential stability. Additionally, the slightly positive values in Fu's Fs, Raggedness (r), and Ramos-Onsins and Rozas (R2) statistics suggested a lack of recent significant selective pressures or population expansions. Furthermore, the presence of genetic differentiation and gene flow among T. evansi populations highlighted ongoing evolutionary processes. These findings collectively depicted a complex genetic landscape, suggesting both stability and ongoing evolutionary dynamics within the Indian population of T. evansi. The findings of this study are important for understanding the evolutionary history and population dynamics of T. evansi, and they may help us develop effective control strategies.

Repurposing pantoprazole in combination with systemic therapy in advanced head and neck squamous cell carcinoma: a phase I/II randomized study.

Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / - intravenous (IV) pantoprazole. The primary endpoint in phase I was to determine the maximum safe dose of intravenous pantoprazole, whereas it was progression-free survival (PFS) in phase II. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov'18 and Oct'20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07-3.19) in the pantoprazole arm and 2.5 months (95% CI 2.04-3.81, HR, 1.14; 95% CI 0.78-1.66; P = 0.48) in the standard arm. Response rates were similar; pantoprazole arm 8.5%, standard arm 6.6%; P = 0.175. Overall survival was also similar; 5.6 months (95% CI 4.47-8.51) in the pantoprazole arm and 5.4 months (95% CI 3.48-8.54, HR 1.06; 95% CI 0.72-1.57; P = 0.75) in the standard arm. Grade ≥ 3 toxicities were similar. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.

Self-Reported Persistent Symptoms at 18 Months and Above Among COVID-19 Non-hospitalized Patients: A Prospective Cohort Study.

INTRODUCTION: Since the beginning of the pandemic in early 2020, there have been numerous reports of symptoms that have lingered due to COVID-19. However, there is a lack of data concerning these persistent symptoms in non-hospitalized patients. This study sought to examine the prevalence of persistent symptoms at 18 months and beyond following the diagnosis of COVID-19 non-hospitalized patients. METHODS: A prospective cohort study comprised 212 non-hospitalized adult patients consecutively assessed from data available at tertiary care institutions through telephone interviews. During the interview, participants were routinely questioned about whether they were still experiencing any post-infection symptoms at the time of the study. RESULTS: Total 212 took part in the 18-month or longer follow-up survey. The most commonly reported symptoms during the acute phase were fever (n=149, 70.3%), weakness (n=118, 55.7%), and sore throat (n=100, 47.2%). At the 18-month and above follow-up, 167 patients (78.7%) reported at least one symptom continuing. The most common symptom at this time point was fatigue (n=109, 51.4%), followed by joint pain (n=57, 26.8%), and exertional dyspnea (24.5%). The possibility of symptoms returning after an 18-month follow-up and beyond was significantly lower in patients who had taken the COVID-19 vaccine (OR=0.29; 95% CI: 0.112-0.749; p=0.011) and those did not infect a second time (OR=0.232; 95% CI: 0.057-0.93; p=0.04). CONCLUSION: The present study reveals that clinical complications persist even at 18 months and beyond during follow-up, with a prevalence similar to earlier follow-up periods, regardless of the severity of the initial COVID-19 infection.

Molecular investigation of bovine tropical theileriosis outbreak in an organized dairy cattle farm in Madhya Pradesh, India.

The present study aimed to investigate an outbreak of Theileria annulata (T. annulata) infection in an organized dairy cattle farm in Madhya Pradesh, India, using clinical and molecular techniques. Following the deaths of two crossbred cattle in March 2021, 43 blood samples were collected from infected and apparently healthy animals and examined by blood smear and polymerase chain reaction (PCR) techniques. The blood smear examination showed that 23.25% of samples were positive for Theileria organisms, while conventional PCR targeting the 18S ribosomal RNA (18S rRNA) and T. annulata merozoite surface antigen-1 (TAMS-1) genes revealed that 32.55% of samples were positive for T. annulata. PCR targeting cytochrome b (Cytb) gene showed 46.51% of samples were positive for T. annulata. Haematological analysis confirmed clinical signs of infection in affected animals, which were treated with buparvaquone @ 2.5 mg/kg body weight intramuscularly along with supportive medicine. Two 18S rRNA gene amplicons were sequenced and analysed in a phylogenetic tree and haplotype network with 54 Indian and 38 foreign sequences. The phylogenetic tree revealed two groups with a high posterior probability and bootstrap value, while the haplotype network revealed 35 haplotypes, with haplotype 1 (H1) being the most abundant and several single haplotypes clustering around it, indicating fast and widespread expansion. Genetic diversity indices and neutrality tests confirmed that the population was expanding. These studies highlight the significance of prompt and precise diagnosis and management of T. annulata outbreaks and provide insights into its evolutionary history and population dynamics of T. annulata in India, which could aid improving disease preventive and control strategies.

Traditional complementary and alternative medicine (TCAM) for diabetic foot ulcer management: A systematic review.

Diabetic Foot Ulcers (DFUs) are a devastating micro-vascular complication of diabetes with an increased prevalence and incidence and high rate of morbidity and mortality. Since antibiotics are frequently used to treat DFU, managing the condition has proven to be extremely challenging and may eventually lead to the development of antibiotic resistance. Scientists from around the world are working to develop an alternative solution to the problem of drug resistance by exploring complementary and alternative medicines that may be obtained from natural sources. Hence, the review aims to comprehensively report the information on the natural treatments and therapy used to manage DFU. All of the information described in the current study was gathered from electronic scientific resources, including Google Scholar, PubMed, Scopus, Science Direct, and Springer Link. Findings from the current review revealed the pre-clinical and clinical utility of 18 medicinal plants, 1 isolated compound, 7 polyherbal formulations including herbal creams, a few micronutrients including vitamins and minerals, insect products such as propolis, honey and, Maggot debridement therapy for the treatment and management of DFU. Natural therapies possess better efficacy, low cost, and shorter duration of treatment when compared with the conventional treatments; hence, all information made available about them is crucial to alter the direction of treatment. Furthermore, the data presented in this review are up to date on the potential efficacy of natural complementary medicines for alleviating DFU problems in in vitro and in vivo tests, as well as clinical studies.

Molecular and genetic diversity in isolates of Trypanosoma evansi from naturally infected horse and dogs by using RoTat 1.2 VSG gene in Madhya Pradesh, India.

BACKGROUND: Trypanosoma evansi is a protozoan parasite that can infect a wide range of animals and is widespread around the world. In this study, we analyzed four fatal cases of T. evansi infection using clinical, parasitological, and molecular approaches. We also explored the genetic diversity, demographic history, and population-genetic structure of T. evansi using available Rode Trypanozoon antigenic type (RoTat) 1.2 gene sequences. METHODS AND RESULTS: Clinical findings of infected animals revealed high fever, anemia, weakness, and anorexia. The animals were treated with diminazene aceturate, which was moderately effective, and hematobiochemical parameters showed changes in hemoglobin and glucose levels. The molecular and genetic diversity of T. evansi was analyzed using the RoTat 1.2 VSG gene. Phylogenetic and haplotype analysis revealed two distinct clusters of T. evansi circulating in India. The genetic diversity indices, neutrality tests, gene flow, and genetic differentiation outcomes confirmed the genetic diversity of the T. evansi population, with a lack of uniformity. The identification of two distinct clusters, exhibiting differential demographic histories and evolutionary forces, implies that the clusters may have undergone independent evolutionary trajectories or experienced different environmental pressures. CONCLUSION: The present findings underlined the need of an early and precise diagnosis in order to treat and control T. evansi infections, and the RoTat 1.2 VSG gene is an important genetic marker for understanding the genetic diversity and evolutionary history of T. evansi. This knowledge can be used to create tailored strategies to control and manage the infection in an endemic region.

National Cancer Grid Virtual Tumor Boards of Head and Neck Cancers: An Innovative Approach to Multidisciplinary Care.

PURPOSE: Virtual tumor board (VTB) via videoconference facility involving multiple specialists in the decision making for various tumors is well accepted, especially in high-income countries. Information on virtual tumor boards for head and neck cancers especially from low- and middle-income countries is sparse. In this study, we have audited the findings of the National Cancer Grid VTBs performed for head and neck cancers. METHODS: All patients discussed in the head and neck VTBs at our center between December 2016 and February 2022 were included in the study. Details such as the type of institute sending patients for discussion, its location, subsites within the head and neck region, histopathology, treatment setting or question for the VTB, and availability of guidelines for such patient scenarios were assessed. Also, a survey was sent to assess the usefulness of the VTBs. RESULTS: A total of 208 patients were discussed in 54 VTB sessions. The most common head and neck sites discussed in the VTBs were the oral cavity (n = 64, 30.7%) followed by skull base/nose and paranasal sinuses/eyelid-orbit tumors (n = 49, 23.5%). Nonsquamous cell carcinoma was the most common histopathology discussed; recurrent cancers/residual diseases were the most common treatment settings (n = 134, 64.4%) for which there were no existing guidelines. Survey results showed that most VTB decisions were implementable, and respondents felt that VTBs were a useful educational tool as well. CONCLUSION: Our study affirms the feasibility of VTBs in low- and middle-income countries' health care systems for managing uncommon malignancies and clinical situations, which act as an important educational platform.

Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation.

PURPOSE: There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS: This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS: The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION: The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].

An integrated computational approach towards the screening of active plant metabolites as potential inhibitors of SARS-CoV-2: an overview.

COVID-19 and its causative organism SARS-CoV-2 paralyzed the world and was designated a pandemic by the World Health Organization in March 2020. The worldwide health system is trying to discover an effective therapeutic measure since no clinically authorized medications are present. Screening of plant-derived pharmaceuticals may be a viable technique to fight COVID-19 in this vital situation. This review discusses the potential application of in silico approaches in developing new therapeutic molecules related to preventing SARS-CoV-2 infection. Also, it describes the binding affinity of various phytoconstituents with distinct SARS-CoV-2 target sites. In this perspective, an extensive literature survey was carried out to find the potential phytoconstituents to develop new therapeutic entities to treat COVID-19 in different online academic databases and books. Data retrieved from databases were analyzed and interpreted to conclude that many phytochemicals will bind with the 3-chymotrypsin-like (3CLpro) and papain-like proteases (PLpro), spike glycoprotein, ACE-2, NSP15-endoribonuclease, and E protein targets of SARS-CoV-2 main protease using in silico molecular docking approach. The present investigations reveal that phytoconstituents such as curcumin, apigenin, chrysophanol, and gingerol are significantly binding with spike glycoprotein; laurolistine, acetoside, etc. are bound with Mpro for anti-SARS-CoV-2 therapies. Using virtual applications of in silico studies, the current study constitutes a progressive data analysis on the mechanism of binding efficiency of distinct classes of plant metabolites against the active sites of SARS-CoV-2. Furthermore, the current review also demonstrates the fundamental necessity of the alternative and complementary medicine for future therapeutic uses of phytoconstituents by phytochemists in the fight against COVID-19.

Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study.

PURPOSE: The regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS). METHODS: This was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m2 once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS. RESULTS: One hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively (P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively (P = .744). CONCLUSION: To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.

Extramural vascular invasion as an independent prognostic marker in locally advanced rectal cancer: propensity score match pair analysis.

BACKGROUND: In rectal cancers, presence of extramural vascular invasion on MRI (mrEMVI) is associated with poor survival. The independent influence of mrEMVI in the presence of other prognostic factors has not been previously analyzed using match pair analysis. PATIENTS AND METHODS: Consecutive 92 patients having mrEMVI at presentation treated between January 2016 and December 2018 were matched with 92 patients (1:1) without mrEMVI. Matching parameters were T stage, mesorectal fascia involvement, and tumor differentiation. The presence and absence of mrEMVI were correlated to outcomes. An event was defined as locoregional failure or distant metastasis or poor response to chemoradiation rendering the rectal tumor as inoperable. RESULTS: At 3 years, in the mrEMVI-positive cohort, 59% had an event and in the mrEMVI-negative cohort, 45% had an event (p = 0.026). Local control was 90.2% (12recurrences in 122 who underwent surgery), two recurrences in the mrEMVI-positive cohort and ten patients in the mrEMVI-negative cohort, which missed statistical significance (p = 0.06). Distant metastasis-free survival was significantly worse in the mrEMVI-positive cohort versus the mrEMVI-negative cohort (58.2% vs. 69.4%) (p = 0.022). Similarly, Overall survival was significantly inferior in mrEMVI-positive cohort compared to the mrEMVI-negative cohort (57% vs. 72.4%) (p = 0.02). The multivariate regression analysis confirmed the independent predictive value of mrEMVI.  CONCLUSION: Extramural vascular invasion detected through MRI is an independent risk factor for distant metastasis in the locally advanced carcinoma rectum. Aggressive treatment regimens like total neoadjuvant treatment should be considered in these cases pending randomized control studies.

THERMOD: Development of a Cost Effective Solution for Integrated Sensing and Logging.

With the outbreak of the Covid-19 pandemic, vaccination has become mandatory. Further, for effective results, the vaccines should be stored within the recommended temperature range, typically between 2°C to 8°C, transported safely without any mishandling and temperature excursion. In order to assure vaccine potency, it is essential to have detailed information on the entire temperature data recorded at user-defined intervals. In this paper, we develop functionality interaction to bring different sensors, memory, and processing units to an integrated platform, providing a compact, power-efficient, and low-cost commercial TemperatuRE, Humidity, and MOvement Data-logger (THERMOD). Moreover, the THERMOD hardware is packed with interactive algorithms that address the aforementioned concerns and log the real-time temperature and jerks (3-dimensional movement) encountered throughout the journey, and the logged data can be retrieved by plugging THERMOD into the host computer/laptop. The THERMOD hardware formulation and algorithm embedding have been done in the institution lab, which enables end-to-end storage and monitoring. Also, the proposed design is built with the defined standards by health organizations, e.g., WHO. Further, to validate the proficiency of the proposed design, comparative analysis has been done; a) a cost analysis has been done to state the cost efficiency of the proposed solution, b) real-time power performance graphs have been plotted which depict that THERMOD outperforms the existing solutions. Moreover, a number of experiments were performed for the validation of the proposed design.