Particle-Hole Character of the Higgs and Goldstone Modes in Strongly Interacting Lattice Bosons.

We study the low-energy excitations of the Bose-Hubbard model in the strongly interacting superfluid phase using a Gutzwiller approach. We extract the single-particle and single-hole excitation amplitudes for each mode and report emergent mode-dependent particle-hole symmetry on specific arc-shaped lines in the phase diagram connecting the well-known Lorentz-invariant limits of the Bose-Hubbard model. By tracking the in-phase particle-hole symmetric oscillations of the order parameter, we provide an answer to the long-standing question about the fate of the pure amplitude Higgs mode away from the integer-density critical point. Furthermore, we point out that out-of-phase symmetric oscillations in the gapless Goldstone mode are responsible for a full suppression of the condensate density oscillations. Possible detection protocols are also discussed.

Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection.

Supplementary methods to identify acute rejection and to distinguish rejection from infection may improve clinical outcomes for lung allograft recipients. We hypothesized that distinct bronchoalveolar lavage (BAL) cell profiles are associated with rejection and infection. We retrospectively compared 2939 BAL cell counts and immunophenotypes against concomitantly obtained transbronchial biopsies and microbiologic studies. We randomly assigned 317 subjects to a derivation or validation cohort. BAL samples were classified into four groups: infection, rejection grade ≥A1, both or neither. We employed generalized estimating equation and survival modeling to identify clinical predictors of rejection and infection. We found that CD25(+) and natural killer cell percentages identified a twofold increased odds of rejection compared to either the infection or the neither infection nor rejection groups. Also, monocytes, lymphocytes and eosinophil percentages were independently associated with rejection. A four-predictor scoring system had high negative predictive value (96-98%) for grade ≥A2 rejection, predicted future rejection in the validation cohort and predicted increased risk of bronchiolitis obliterans syndrome in otherwise benign samples. In conclusion, BAL cell immunophenotyping discriminates between infection and acute rejection and predicts future outcomes in lung transplant recipients. Although it cannot replace histopathology, immunophenotyping may be a clinically useful adjunct.

A meta-analysis comparing the safety and efficacy of azithromycin over the alternate drugs used for treatment of uncomplicated enteric fever.

BACKGROUND: Drug-resistant typhoid fever is a major clinical problem globally. Emergence of multidrug-resistant (MDR) S. Typhi has complicated therapy by limiting treatment options. OBJECTIVES: A meta-analysis was planned to determine the strength of evidence supporting use of azithromycin over the alternate drugs available for treatment of uncomplicated typhoid fever. MATERIALS AND METHODS: Studies were identified using electronic database such as MEDLINE and other data at the National Library of Medicine assessed using PUBMED search engine as well as Cochrane Clinical Trial Register. Randomized control trials (RCTs) comparing azithromycin with chloramphenicol, fluoroquinolones and cephalosporins in culture-proven enteric fever were included. Data was extracted and methodological quality was assessed. Risk ratio (RR) with 95% confidence intervals was estimated for the dichotomous outcomes and mean difference (MD) with 95% confidence was estimated for continuous data. Primary outcomes studied were clinical failure (CF), microbiological failure, and relapse. RESULTS: A total of seven RCTs involving 773 patients met with our inclusion criteria. In comparison to older fluoroquinolones, azithromycin is marginally better in reducing the chance of CF with RR 0.46 (95% CI 0.25-0.82), while in comparison to ceftriaxone, it significantly reduced the chance of relapse with RR 0.1 (95% CI 0.01- 0.76). There were no serious adverse events reported in any of the trials. CONCLUSION: Azithromycin can be recommended as a second-line drug in MDR typhoid fever, however, large trials involving pediatric age group patients are recommended to arrive at a definite conclusion.

Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Origin of excess low-energy states in a disordered superconductor in a Zeeman field.

Tunneling density of states measurements of disordered superconducting Al films in high Zeeman fields reveal a significant population of subgap states which cannot be explained by standard BCS theory. We provide a natural explanation of these excess states in terms of a novel disordered Larkin-Ovchinnikov phase that occurs near the spin-paramagnetic transition at the Chandrasekhar-Clogston critical field. The disordered Larkin-Ovchinnikov superconductor is characterized by a pairing amplitude that changes sign at domain walls. These domain walls carry magnetization and support Andreev bound states that lead to distinct spectral signatures at low energy.

A meta-analysis of low-dose aspirin for prevention of preeclampsia.

BACKGROUND: Low-dose aspirin (LDA) is widely used for prevention of preeclampsia. However, conflicting results have been obtained from various studies. AIM: The aim of our study was to evaluate the effect of LDA in prevention of preeclampsia in high-risk and low-risk women. MATERIALS AND METHODS: A total of 19 randomized control trials were identified using PUBMED search engine and Cochrane Clinical Trial register. The study population was divided into high-risk and low-risk groups. The effect measured was incidence of preeclampsia in women taking either LDA or placebo where the relative risk (RR) and the 95% confidence interval (CI) were calculated for both groups. RESULTS: A total of 28237 women were studied, out of which 16550 were in the low-risk group while 11687 were in the high-risk group. The overall incidence of preeclampsia was 7.4%. With the aspirin group it was 6.9% while in the placebo group it was 7.8%. In the high-risk group there was 21% reduction in the risk of preeclampsia associated with the use of aspirin (RR 0.79, 95% CI 0.65-0.97). However, LDA is not effective in reducing the risk in low-risk population (RR 0.86, 95% CI 0.64-1.17). CONCLUSION: LDA has a small effect in the prevention of preeclampsia in women considered to be at high risk for the disease. However, it is not effective in reducing the risk in the low-risk group.

Addressing species specific metabolism and solubility issues in a quinoline series of oral PDE4 inhibitors.

Species specific conversion of the lead PDE4 inhibitor 1 to the quinolone 3 was identified as the major route of metabolism in the cynomolgus monkey. Modification of the template to give the cinnoline 9 retained potency and selectivity, and greatly improved the pharmacokinetic profile in the cynomolgus monkey compared with 1. Additional SAR studies aimed at improving the solubility of 9 are also described.

Possible treatment and strategies for COVID-19: review and assessment.

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.

Realization of a push-me-pull-you swimmer at low Reynolds numbers.

Locomotion at low Reynolds numbers encounters stringent physical constraints due to the dominance of viscous over inertial forces. A variety of swimming microorganisms have demonstrated diverse strategies to generate self-propulsion in the absence of inertia. In particular, ameboid and euglenoid movements exploit shape deformations of the cell body for locomotion. Inspired by these biological organisms, the 'push-me-pull-you' (PMPY) swimmer (Avron J Eet al2005New J. Phys.7234) represents an elegant artificial swimmer that can escape from the constraints of the scallop theorem and generate self-propulsion in highly viscous fluid environments. In this work, we present the first experimental realization of the PMPY swimmer, which consists of a pair of expandable spheres connected by an extensible link. We designed and constructed robotic PMPY swimmers and characterized their propulsion performance in highly viscous silicone oil in dynamically similar, macroscopic experiments. The proof-of-concept demonstrates the feasibility and robustness of the PMPY mechanism as a viable locomotion strategy at low Reynolds numbers.

Population-based stroke survey in Mumbai, India: incidence and 28-day case fatality.

OBJECTIVES: The aims of this study were (1) to establish a prospective community-based stroke registry in Mumbai of subjects having 'first-ever stroke' (FES) and (2) to collect standardized data on annual incidence, stroke subtypes, and case fatality rate at 28 days during the years 2005 and 2006. BACKGROUND: An estimated 5.8 million people died from stroke (cerebrovascular disease) in 2005, two thirds of them were from low-/middle-income countries but reliable population-based studies are scarce. METHODS: The manual on WHO STEPwise approach to stroke surveillance (STEPS Stroke; http://www.who.int/chp/steps/Manual pdf) was the operational protocol. We selected a well-defined community (H-district) having verifiable census data and being representative of the population structure of Mumbai (Bombay). Of 337,391 permanent residents, 156,861 persons between the age of 25 and 94+ years who were eligible for survey were screened. The responses to a predefined questionnaire (version 2.0) were entered in coded data sheets for analysis. RESULTS: During the 2-year study period (January 2005 to December 2006), 456 (238 males and 218 females) had FES, indicating an annual incidence in subjects of 25 years and above of 145/100,000 persons (CI 95%: 120-170); for males it is 149/100,000 persons (CI 95%: 120-170) and for females it is 141/100,000 persons (CI 95%: 120-160). The age-standardized rate for study population (both sexes) by the direct method using Segi's 1996 world population is 152/100,000/year (CI 95%: 132-172). Stroke diagnosis was supported by computed tomography in 407 (89.2%) of 456 FES cases: 366 (80.2%) had ischemic stroke, 81 (17.7%) had hemorrhagic stroke and 9 (1.9%) were in the unspecified category. The mean age was 66 +/- (SD) 13.60 years, women were older as compared to men (mean age 68.9 +/- 13.12 years vs. 63.4 +/- 13.53 years). Case fatality: at 28 days, 320 (70%) of 456 FES cases were still alive and 136 (29.8%) had died. Of the 320 surviving patients 38.5% had moderate to severe disability by the modified Rankin scale. CONCLUSIONS: The results of Mumbai stroke study, using uniform definitions and methodologies, show that the annual standardized incidence rates, stroke subtypes and case fatality rate are very similar to those reported from developed nations. To plan effective intervention and prevention strategies, standardized data in representative samples of regional populations are urgently needed.

Stomaplasty--anterior advancement flap and lateral splaying of trachea, a simple and effective technique.

BACKGROUND: Stomal stenosis after laryngectomy is a common and distressing complication. Once sets in, it is generally progressive, causes problems and needs active intervention. AIM: To evaluate effectiveness of new simple method of stomaplasty in solving troublesome complication of stoma stenosis. SETTINGS AND DESIGN: Charts of eight patients who underwent modified stomaplasty and completed 1 year were reviewed. MATERIALS AND METHODS: A modified anterior advancement flap and lateral splaying of trachea for stoma plasty are described. This involves excision of scar tissue of the anterior two-third of trachea and interposition of the defect with an inferiorly based triangular skin flap. The tracheo-esophageal-prosthesis (TEP) site is left untouched. STATISTICAL ANALYSIS: Outcome were measured in relation with need for further stenting or any other revision procedure required and ability to use TEP for speech production. RESULTS: Eight patients underwent stoma revision surgery. Median preprocedure stoma diameter was 10 mm vertically (range 8-12 mm) and 6 mm horizontally (range 5-10 mm). This could be improved to 25 mm (range 22-30 mm) vertically and 16 mm (range 14-20 mm) horizontally after stoma revision. At 1-year follow-up, the median measurements were 20 mm (range 16-26) vertically and 14 mm (range 12-18) horizontally. Postprocedure, one patient required intermittent stenting at nighttime. All patients could use the TEP effectively. One patient who underwent salvage laryngectomy following chemoradiotherapy developed flap dehiscence. CONCLUSIONS: This is a simple and effective technique for stomaplasty. All patients treated with this technique had adequately large stoma for breathing and use of TEP.

Coexistence of squamous cell carcinoma with dermoid cyst of ovary.

A 40-year-old female presented with pain and enlargement of abdomen since last 6 months. A mass was felt over right iliac fossa. Ultrasonography showed partly cystic and solid area in mass arising from ovary. A tooth-like structure was also seen. Dermoid cyst was the diagnosis offered. Laparotomy was performed. Ovarian mass with hair, a tooth and putty-like material was present. Solid white area with thickened wall was found. Histopathology confirmed the findings of dermoid cyst and the thickened area showed squamous cell carcinoma with areas showing keratinous material and giant cell reaction which was also seen at the periphery of tumor areas. Left ovary was normal and no deposits of tumor were seen. Postoperative period was uneventful.

Imaging quantum fluctuations near criticality.

A quantum phase transition (QPT) occurs between two competing phases of matter at zero temperature, driven by quantum fluctuations. Though the presence of these fluctuations is well established, they have not been locally imaged in space and their local dynamics has not been studied so far. We use a scanning superconducting quantum interference device to image quantum fluctuations in the vicinity of the QPT from a superconductor to an insulator. We find fluctuations of the diamagnetic response in both space and time that survive well below the transition temperature, demonstrating their quantum nature. The fluctuations appear as telegraph-like noise with a range of characteristic times and a non-monotonic temperature dependence, revealing unexpected quantum granularity. The lateral dimension of these fluctuations grows towards criticality, offering a new measurable length scale. Our results provide physical insight about the reorganization of phases across a QPT, with implications for any theoretical description. This paves a new route for future quantum information applications.

Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes.

Nucleic acid immunization is a novel vaccination technique to induce antigen-specific immune responses. We have developed expression cassettes for cell surface markers CD80 and CD86, two functionally related costimulatory molecules that play an important role in the induction of T cell-mediated immune responses. Coimmunization of these expression plasmids, along with plasmid DNA encoding for HIV-1 antigens, did not result in any significant change in the humoral response; however, we observed a dramatic increase in cytotoxic T-lymphocyte (CTL) induction as well as T-helper cell proliferation after the coadministration of CD86 genes. In contrast, coimmunization with a CD80 expression cassette resulted in a minor, but positive increase in T-helper cell or CTL responses. This strategy may be of value for the generation of rationally designed vaccines and immune therapeutics.

Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs.

The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.

Marine Microbes as a Potential Source of Cellulolytic Enzymes.

Marine environment hosts the wide range of habitats with remarkably high and diverse microbial populations. The ability of marine microorganisms to survive in extreme temperature, salinity, and pressure depends on the function of multivarious enzyme systems that in turn provide vast potential for biotechnological exploration studies. Therefore, the enzymes from marine microorganism represent novel bio catalytic potential with stable and reliable properties. Microbial cellulases constitute a major group of industrial enzymes that find applications in various industries. Majority of cellulases are of terrestrial origin, and very limited research has been carried out to explore marine microbes as a source of cellulases. This chapter presents an overview about the types of marine polysaccharases, classification and potential applications of cellulases, different sources of marine cellulases, and their future perspectives.

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine.

Nucleic acid immunization has been investigated as immunotherapy for infectious diseases as well as for treating specific types of cancers. In this approach, nucleic acid expression cassettes are directly inoculated into the host, whose transfected cells become the production source of novel and possibly immunologically foreign protein. We have developed a DNA vaccine construct which encodes for PSA by cloning a cDNA for PSA into a mammalian expression vector under control of a CMV promoter. We investigated and characterized the immunogenicity of PSA DNA expression cassettes in mice. PSA-specific immune responses induced in vivo by immunization were characterized by enzyme-linked immunosorbent assay (ELISA), T helper proliferation cytotoxic T lymphocyte (CTL), and flow cytometry assays. We observed a strong and persistent antibody response against PSA for at least 180 days following immunization. In addition, a significant T helper cell proliferation was observed against PSA protein. Using synthetic peptides spanning the PSA open frame, we identified four dominant T helper epitopes of PSA. Furthermore, immunization with PSA plasmid induced MHC Class I CD8+ T cell-restricted cytotoxic T lymphocyte response against tumor cell targets expressing PSA. The prostate represents a very specific functional organ critical for reproduction but not for the health and survival of the individual. Understanding the immunogenicity of PSA DNA immunization cassettes offers insight into the possible use of this tumor-associated antigen as a target for immunotherapy. These results demonstrate the ability of the genetic PSA to serve as a specific immune target capable of generating both humoral and cellular immune responses in vivo.

Pathology of advanced buccal mucosa cancer involving masticator space (T4b).

BACKGROUND: Buccal mucosa cancer involving masticator space is classified as very advanced local disease (T4b). The local recurrence rate is very high due to poor understanding of the extent of tumor spread in masticator space and technically difficult surgical clearance. The objective of this study is to understand the extent of tumor spread in masticator space to form basis for appropriate surgical resection. MATERIALS AND METHODS: All consecutive patients with T4b-buccal cancer underwent compartment resection, with complete anatomical removal of involved soft-tissue structures. Specimens were systematically studied to understand the extent of invasion of various structures. The findings of clinical history, imaging and pathologic evaluation were compared and the results were evaluated. RESULTS: A total of 45 patients with advanced buccal cancer (T4b) were included in this study. The skin, mandible and lymph nodes were involved in 30, 24 and 17 cases respectively. The pterygoid muscles were involved in 34 cases (medial-pterygoid in 12 and both pterygoids in 22 cases) and masseter-muscle in 32 cases. Average distance for soft-tissue margins after compartment surgery was 2 cm and the margins were positive in 3 cases. The group with involvement of medial pterygoid muscle had safest margin with compartment surgery while it was also possible to achieve negative margins for group involving lateral pterygoid muscle and plates.The involvement of pterygomaxillary fissure was area of concern and margin was positive in 2 cases with one patient developing local recurrence with intracranial extension. At 21 months median follow-up (13-35 months), 38 patients were alive without disease while two developed local recurrence at the skull base. CONCLUSIONS: T4b buccal cancers have significant soft-tissue involvement in the masticator space. En bloc removal of all soft-tissues in masticator space is advocated to remove tumor contained within space. The compartment surgery provides an opportunity to achieve negative margins for cancers actually contained within masticator space.It is inappropriate to club all patients with masticator space involvement in one group.

Emergence of coherence in the charge-density wave state of 2H-NbSe2.

A charge-density wave (CDW) state has a broken symmetry described by a complex order parameter with an amplitude and a phase. The conventional view, based on clean, weak-coupling systems, is that a finite amplitude and long-range phase coherence set in simultaneously at the CDW transition temperature T(cdw). Here we investigate, using photoemission, X-ray scattering and scanning tunnelling microscopy, the canonical CDW compound 2H-NbSe2 intercalated with Mn and Co, and show that the conventional view is untenable. We find that, either at high temperature or at large intercalation, CDW order becomes short-ranged with a well-defined amplitude, which has impacts on the electronic dispersion, giving rise to an energy gap. The phase transition at T(cdw) marks the onset of long-range order with global phase coherence, leading to sharp electronic excitations. Our observations emphasize the importance of phase fluctuations in strongly coupled CDW systems and provide insights into the significance of phase incoherence in 'pseudogap' states.