Increasing global accessibility to high-level treatments for cervical cancers.

Human papillomaviruses (HPV)-related gynecological cancers are a major health care issue, and a leading cause of cancer death in low- and middle-income countries (LMIC). In 2020, the World Health Organization launched a program aimed at cervical cancer elimination, by screening and vaccination strategies. Offering the best possible care to women diagnosed with invasive cancer is a complementary objective. Treatment of cervical cancer as per modern standards is complex and multimodal, mainly relying on surgery, external-beam radiotherapy (+/-chemotherapy) and brachytherapy. In parallel with the pivotal role of multidisciplinary discussion, international societies provide guidance to define the most effective and least toxic anti-cancer strategy, homogenize treatment protocols and provide benchmark quality indicators as a basis for accreditation processes. The challenge is to offer the appropriate diagnostic workup and treatment upfront and to avoid non- evidence-based treatment that consumes resources, impairs quality of life (QoL), and compromises oncological outcome. Various strategies may be applied for improving treatment quality: development of surgical mentorship, companion-training programs and international cooperation. The lack of radiotherapy/brachytherapy facilities is a major concern in LMIC. Reinforcing international support in terms of education, training, research and development and technical cooperation with national projects is required to increase access to minimum requirements but also introduce modern techniques, upgrade radiotherapy/brachytherapy services, and expand access to modern systemic treatments. In countries with robust economies, compliance to standards should also be increased. Integrative cancer care and multidisciplinary approaches are needed to tackle the dual challenge of increasing cure rates while minimizing QoL impairment. Appropriate dimensioning of the resources to avoid harmful treatment delays and access to expert referral centers is also a priority.

Effects of triple-drug therapy with nitazoxanide, high-dose ribavirin and peginterferon-α-2a in patients with chronic hepatitis C.

AIM: The historical standard of care for patients with chronic hepatitis C virus (HCV) was peginterferon (PEG IFN) and ribavirin combination therapy, yielding sustained virological response (SVR) rates of 38-52% in HCV genotype 1 patients. This study evaluated a novel three-drug regimen of nitazoxanide and high-dose ribavirin as lead-in therapy, followed by PEG IFN-α-2a in triple therapy. METHODS: A prospective, open-label pilot study was conducted in treatment-naive patients with HCV genotype 1. Patients received nitazoxanide 500 mg twice a day for 2 weeks, then nitazoxanide plus ribavirin 1400 mg/day for 2 weeks, then nitazoxanide plus ribavirin plus PEG IFN-α-2a 180 µg weekly for 12 weeks, followed by ribavirin plus PEG IFN-α-2a for 12 weeks (48 weeks if HCV RNA negative after week 24). Primary outcome was SVR. Other outcomes included very rapid virological response (VRVR), rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and safety and tolerability. RESULTS: Thirty-three patients with a mean age of 46 years, detectable HCV RNA (64% with <600 000 IU/mL), and METAVIR fibrosis scores (F1:F2:F3) of 15%:49%:36% were enrolled. Outcomes were as follows: SVR, 67% (22/33); VRVR, 39% (13/33); RVR, 48% (16/33); EVR, 70% (23/33); and ETR, 67% (22/33). Most patients required at least one growth factor. Two patients discontinued because of adverse events. CONCLUSION: This three-drug regimen was effective in achieving SVR in patients with HCV genotype 1. No patients relapsed, and the toxicity profile was favorable. Further studies on the role of nitazoxanide in the treatment of chronic HCV are warranted.

Global taxonomic, functional, and phylogenetic diversity of bees in apple orchards.

An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators and identification of the drivers of pollinator community changes across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated diversity drivers for 644 bee species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographical biomes. Our findings reveal significant taxonomic dissimilarity among biogeographical zones. Interestingly, despite this dissimilarity, species from different zones share similar higher-level phylogenetic groups and similar ecological and behavioural traits (i.e. functional traits), likely due to habitat filtering caused by perennial monoculture systems managed intensively for crop production. Honey bee species dominated orchard communities, while other managed/manageable and wild species were collected in lower numbers. Moreover, the presence of herbaceous, uncultivated open areas and organic management practices were associated with increased wild bee diversity. Overall, our study sheds light on the importance of large-scale analyses contributing to the emerging fields of functional and phylogenetic diversity, which can be related to ecosystem function to promote biodiversity as a key asset in agroecosystems in the face of global change pressures.

Novel endoscopic delivery modality of infrared coagulation therapy for internal hemorrhoids.

BACKGROUND: A novel endoscopic delivery system for infrared coagulation therapy (IRC) has been designed recently. IRC is a well-established treatment for symptomatic internal hemorrhoids. Patients frequently undergo lower endoscopy before hemorrhoid treatment to eliminate other sources of bleeding. Current treatment options are difficult to perform without an anal retractor, adequate lighting, and specialized instruments. Endoscopic IRC is an attractive alternative to standard IRC, because it can be performed during the lower endoscopy. TECHNIQUE: Endoscopic IRC utilizes infrared radiation generated by a control box, which is applied to the tissue through a flexible, fiber optic light guide (Precision Endoscopic Infrared Coagulator™). The light guide is placed through the colonoscope or flexible sigmoidoscope in the same chamber as other endoscopic instruments. METHODS: A retrospective review was performed using a prospectively collected database. A standardized protocol was utilized in all patients. Patients graded their symptoms before and after therapy by using the visual analog symptom severity scoring system (range, 0-10). These results were analyzed by using the nonparametric Wilcoxon signed-rank test. Exact P values were computed by using the R function wilcox.exact. RESULTS: A total of 55 patients underwent endoscopic IRC for predominately grade II and grade III symptomatic internal hemorrhoids (71 %). There were 22 (40 %) female patients. Posttherapy results indicated a significant improvement in global symptoms (pretreatment average global score = 2.24 vs. posttreatment average global score = 0.28; P < 0.0001). There have been no adverse events reported to date. CONCLUSIONS: Endoscopic IRC provides improved visibility and efficiency, allowing simultaneous treatment of symptomatic internal hemorrhoids at the time of lower endoscopy. Patients experienced significant improvement in their symptoms after a single session of endoscopic IRC. There are a variety of additional endoscopic IRC therapeutic utilities: endoscopic management of angiodysplasia, inflammation, hemostasis, and NOTES applications.

A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori.

OBJECTIVES: Resistance to standard Helicobacter pylori (HP) treatment regimens has led to unsatisfactory cure rates in HP-infected patients. This study was designed to evaluate a novel four-drug regimen (three antibiotics and a proton pump inhibitor (PPI)) for eradication of HP infection in treatment-naive patients. METHODS: Patients with a diagnosis of HP gastritis or peptic ulcer disease confirmed using endoscopy and stool antigen testing were eligible for inclusion in this study. All patients underwent a washout period of 6 weeks from any prior antibiotic or PPI usage. Patients were then randomized to either levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD) therapy for 7 days (LOAD-7) or 10 days (LOAD-10), including levofloxacin 250 mg with breakfast, omeprazole 40 mg before breakfast, nitazoxanide (Alina) 500 mg twice daily with meals and doxycycline 100 mg at dinner, or lansoprozole, amoxicillin, and clarithromycin (LAC) therapy for 10 days, which included lansoprozole 30 mg, amoxicillin 1 g with breakfast and dinner, and clarithromycin 500 mg with breakfast and dinner. HP eradication was confirmed by stool antigen testing at least 4 weeks after cessation of therapy. RESULTS: Intention-to-treat analysis revealed significant differences (P<0.05) in the respective eradication rates of the LOAD therapies (88.9% (80/90) LOAD-10, 90% (81/90) LOAD-7, 89.4% (161/180) for combined LOAD) compared with those receiving LAC, 73.3% (66/90). There were no differences in adverse effects between the groups. CONCLUSIONS: This open-label, prospective trial demonstrates that LOAD is a highly active regimen for the treatment of HP in treatment-naive patients. A large randomized controlled trial is warranted to further evaluate the efficacy of this regimen.

Changing epidemiology of SARS-CoV in the context of COVID-19 pandemic.

SARS-CoV-2 is a new form of ß-coronavirus that has been recently discovered and is responsible for COVID 19 pandemic. The earliest infection can be traced back to Wuhan, China. From there it has spread all over the world. Keeping in view the above perspective, an attempt is made in order to find out the epidemiological pattern of COVID 19 pandemic, if any, in different geo-climatological regions of the world in terms of case incidence and mortality. This study is also an endeavor to review and analyze the gradual changes of the genetic makeup of SARS-CoV from evolutionary and epidemiological perspectives. The raw data of COVID-19 cases and death incidences were collected from the World Health Organization (WHO) website from the time period: 1st April to 6th April, 2020. The data that are utilized here for general and Case fatality rate (CFR) based analysis. Western pacific region, European region and Americas have the greatest number of infected cases (P < 0.001); whereas deaths have been found to be significantly higher in Europe (P < 0.001). Total number of confirmed cases and deaths in south-east Asia are comparatively lower (P < 0.001). Case fatality rate (CFR) has also found significant for European region. SARS-CoV-2 is considered to be a strain of SARS-CoV that has a high rate of pathogenicity and transmissibility. Result indicated that the European region has been affected mostly for both cases and death incidences. The novel mutations in SARS-CoV-2 possibly increase the virus infectivity. Genetic heterogeneity of this virus within the human population might originate as the representatives of naturally selected virus quasispecies. In this context, the presence of the asymptomatic individuals could be a significant concern for SARS-CoV-2 epidemiology. Further studies are required to understand its genetic evolution and epidemiological significance.

Knowledge transfer as a tool towards improvement of cancer care in low- and middle-income countries. 6th European Roundtable Meeting (ERTM), June 14th, 2019, Berlin, Germany.

PURPOSE: To identify key factors for the best practice of knowledge transfer from high-income settings to low- and middle-income settings. RESULTS: Interactive sessions led to the identification of European learnings that can and should be shared beyond Europe. Furthermore, methods were characterised which may lead to successful knowledge transfer with subsequent quality improvement. CONCLUSION: To ensure successful implementation of knowledge and new methods, political support is extremely important. A strong focus should be an improvement of collaboration and network development. Rehabilitation, early and late pallative care, cost effectiveness and long-term follow-up are priorities. Limitations are budget constraints which limit the execution of NCCPs.

Clinical utility of the interaction between lectin and serum prostate specific antigen in prostate cancer.

The present investigation was a lectin-based diagnosis of malignant prostate cancer (PC) by the interaction of phytohemagglutinin (PHA lectin) from Phaseolus vulgaris with the glycan part of serum prostate specific antigen (PSA) of patients with prostatic disorder. This was confirmed by the interaction between PHA and purified PSA obtained from serum by electrophoretic separation and finally by HPLC chromatography. The precipitate of carbohydrate content after binding of PHA with purified PSA of PC was significantly higher than that of benign prostate hyperplasia (BPH) and/or normal serum PSA. The results suggest that there may be a striking difference in glycosylation pattern of PSA between BPH and PC. The cut off value > or = 10 microg/ml of the carbohydrate content of PHA-PSA precipitate indicates strong suspicion for PC irrespective of total serum PSA cut off level > or = 4.0 ng/ml by conventional immunoassay method and this may be taken as a guideline in differentiating PC and BPH. Key words: prostate cancer, BPH, PSA, lectin.

Lactose mother liquor as an alternative nutrient source for microbial concrete production by Sporosarcina pasteurii.

Microbiologically induced calcite precipitation by the bacterium Sporosarcina pasteurii (NCIM 2477) using the industrial effluent of the dairy industry, lactose mother liquor (LML) as growth medium was demonstrated for the first time in this study. The urease activity and the calcite precipitation by the bacterium was tested in LML and compared with the standard media like nutrient media and yeast extract media. Calcite constituted 24.0% of the total weight of the sand samples plugged by S. pasteurii and urease production was found to be 353 U/ml in LML medium. The compressive strength of cement mortar was increased by S. pasteurii in all the media used compared to control. No significant difference in the growth, urease production and compressive strength of mortar among the media suggesting LML as an alternative source for standard media. This study demonstrates that microbial calcite acts as a sealing agent for filling the gaps or cracks and fissures in constructed facilities and natural formations alike.

Strain improvement of Sporosarcina pasteurii for enhanced urease and calcite production.

Phenotypic mutants of Sporosarcina pasteurii (previously known as Bacillus pasteurii) (MTCC 1761) were developed by UV irradiation to test their ability to enhance urease activity and calcite production. Among the mutants, Bp M-3 was found to be more efficient compared to other mutants and wild-type strain. It produced the highest urease activity and calcite production compared to other isolates. The production of extracellular polymeric substances and biofilm was also higher in this mutant than other isolates. Microbial sand plugging results showed the highest calcite precipitation by Bp M-3 mutant. Scanning electron micrography, energy-dispersive X-ray and X-ray diffraction analyses evidenced the direct involvement of bacteria in CaCO3 precipitation. This study suggests that calcite production by the mutant through biomineralization processes is highly effective and may provide a useful strategy as a sealing agent for filling the gaps or cracks and fissures in any construction structures.

Study of 'patterns of care' of ovarian cancer patients in a specialized cancer institute in Kolkata, eastern India.

BACKGROUND: Ovarian cancer is one of the leading cancers in Indian women. The current standard of care is a combination of surgical staging, maximal surgical effort to achieve cytoreduction, and judicious use of chemotherapy. Multimodality therapy can reduce mortality, but the practice and uptake of such therapy in Indian Institutions are not up to the desired level. OBJECTIVES: To study the protocol adherence for ovarian cancer management along with patient compliance and evaluate their effects on survival. MATERIALS AND METHODS: The retrospective study obtained and analyzed data from records of patients operated for ovarian cancer at a Regional Cancer Center in eastern India between January 2002 and December 2006. RESULTS: The records of 202 patients were evaluable. None of the patients who had primary surgery outside the institute had staging information. A substantial number of patients operated at the institute had incomplete surgical staging, inadequate information on residual disease after surgery, and incomplete histology report. Only 20.3% patients could have optimal cytoreduction after surgery. Compliance to chemotherapy was poor. The median overall survival time and disease-free survival time were 24 months and 5 months, respectively. The residual disease after surgery significantly affected the overall survival, but not the disease-free survival. Incomplete chemotherapy was found to adversely affect survival after adjusting for advanced stage and bulky residual disease. CONCLUSION: Management of ovarian cancer is suboptimal even in the specialized cancer institute. Poor patient compliance to chemotherapy is one of the major factors adversely affecting survival from advanced ovarian cancer.

Osmotic adjustment increases water uptake, remobilization of assimilates and maintains photosynthesis in chickpea under drought.

Eight chickpea advanced breeding lines (ABLs) and their parents were evaluated for osmotic adjustment (OA), leaf carbohydrates and gas exchange under dryland field . These (ABLs) were derived from crosses between CTS 60543 x Kaniva and Tyson x Kaniva. Mean leaf water potential (LWP) fell down from -1.00 MPa at pre-stress level to about -2.25 MPa during terminal stress. Relative water content (RWC) showed periodic changes with alternate decrease or increase at certain interval, which also influenced the values of OA (low or high) in number of genotypes e.g. Kaniva, CTS 60543, Tyson and M 75. Significant variation in OA ranging 0.45 to 0.88 MPa was observed at high level of stress at -2.5 MPa. However, none of the genotypes showed stability of OA over the period of stress. Leaf starch declined even at mild stress (LWP, -1.6 MPa) resulting in an increase in hexose sugars and activation state of sucrose-phosphate synthase (SPS) that led to accumulation of sucrose. Both photosynthesis (Pmax) and transpiration decreased concurrently in two chickpea lines M 129 and Tyson with increasing water stress. However, rate of decline in the photosynthesis slowed down even drought was further intensified. The observed periodic changes in OA, RWC and photosynthesis appeared to be associated with drought-induced changes in SPS and carbohydrates which modify water uptake of the leaves.

Production and metabolism of indole acetic acid in roots and root nodules of Phaseolus mungo.

The mature root nodules of Phaseolus mungo (L.), a leguminous pulse, contain higher amount of indole acetic acid (IAA) than non-nodulated roots. The tryptophan pool present in the mature nodule and young roots might serve as a precursor for the IAA production. Presence of IAA metabolising enzymes - IAA oxidase and peroxidase - indicate the metabolism of IAA in the nodules and roots. In culture, the symbiont, isolated from the nodules, produced a high amount of IAA, when tryptophan was supplied in the medium as a precursor. The symbiont preferred l-isomer over the dl- or d-isomer of tryptophan for IAA production. The important physiological implication of the IAA production in the legume-Rhizobium symbiosis is discussed.

Is interferon-alpha and retinoic acid combination along with radiation superior to chemo-radiation in the treatment of advanced carcinoma of cervix?

Locally advanced cervical cancers comprise a large majority of the gynecologic cancers in India and other developing countries. Concurrent chemo-radiation has improved the survival of high risk stage I and stage II cervical cancers. There is no evidence that the same survival benefit has been achieved with chemo-radiation in stage III and stage IV disease. Interferon-alpha and Retinoic acid have synergistic anti-proliferative activity. In combination with radiation, they substantially enhance the sensitivity of the squamous carcinoma cells to radiation. Based on these observations from the in vitro studies, a few clinical trials have evaluated the combination of interferon-alpha and Retinoic acid, concomitant with radiation, to treat cervical cancers. The results from these early trials were encouraging and the combination had minimal toxicities. However, till date, no phase III randomized controlled trial has been done to evaluate this therapeutic modality.

Enhancement of lectin-erythrocyte agglutination by gums.

The erythroagglutinating activity of purified Vicia faba lectin was enhanced in the presence of gums; gum guar caused the highest enhancement. Circular dichroism probe demonstrated 40-57% beta-conformation and 4-23% alpha-conformation of the lectin at pH 7.2 depending upon the analytical methods used. The beta-conformations of untreated and modified V. faba lectins were increased in the presence of gums. The mixing of gum guar with lectin and with modified lectin, respectively, led to the highest values of beta-conformational change in the protein molecule, thereby increasing the number of receptor sites of the lectin molecule. The enhancement of the activity of V. faba lectin in the presence of gum guar might be due to the conformational change of the protein molecule.

Least-squares finite-element scheme for the lattice Boltzmann method on an unstructured mesh.

A numerical model of the lattice Boltzmann method (LBM) utilizing least-squares finite-element method in space and the Crank-Nicolson method in time is developed. This method is able to solve fluid flow in domains that contain complex or irregular geometric boundaries by using the flexibility and numerical stability of a finite-element method, while employing accurate least-squares optimization. Fourth-order accuracy in space and second-order accuracy in time are derived for a pure advection equation on a uniform mesh; while high stability is implied from a von Neumann linearized stability analysis. Implemented on unstructured mesh through an innovative element-by-element approach, the proposed method requires fewer grid points and less memory compared to traditional LBM. Accurate numerical results are presented through two-dimensional incompressible Poiseuille flow, Couette flow, and flow past a circular cylinder. Finally, the proposed method is applied to estimate the permeability of a randomly generated porous media, which further demonstrates its inherent geometric flexibility.

Clinical and Neurologic Manifestation of Minimal Hepatic Encephalopathy and Overt Hepatic Encephalopathy.

Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric manifestations. A combined effort with neuropsychological and psychometric evaluation has to be performed to recognize the syndrome, whereas minimal HE (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed through specialized neuropsychiatric testing. Early diagnosis and treatment may drastically improve the quality of life for many cirrhotic patients. Further research to gain better insight into the pathophysiology and diagnostic accuracy of HE will help determine future management strategies.

Molecular anatomy of CTG expansion in myotonin protein kinase gene among myotonic dystrophy patients from eastern India.

We have studied the CTG repeat sizes in the DMPK gene and six biallelic markers which are in complete linkage disequlibrium with Caucasian DM patients, to identify any common founder haplotype in 30 clinically diagnosed unrelated DM patients from eastern India. Our results revealed that in 27 patients (90%), CTG expansion took place on a DraIII(-) - HhaI(-) - Alu(+) - HinfI(+) - Fnu4H I(-) - TaqI(+) haplotype (haplotype I), similar to what have been published for Caucasoid and other DM patients. However, in three patients (10%), the expansion of CTG repeat was on DraIII(+) - HhaI(+) - Alu(+) - HinfI(-) - Fnu4H I(+) - TaqI(-) background (haplotype II), indicating a new haplotype. The distribution of haplotypes in 52 normal individuals of eastern India revealed that percentage of haplotypes I and II were 23.1% and 7.7% respectively in normal chromosomes. Haplotype II is absent among Caucasian DM patients as well as normal individuals indicating that this particular haplotype may be characteristic of the Indian population. Hum Mutat 16:372, 2000.