Dipole-dipole correlations in the nematic phases of symmetric cyanobiphenyl dimers and their binary mixtures with 5CB.

We report on the temperature dependence of birefringence and of the static dielectric permittivity tensor in a series of binary mixtures between the symmetric, bent-shaped, 1'',9''-bis(4-cyanobiphenyl-4'-yl)nonane (CB9CB) dimer and the monomeric nematogen 5CB. In the studied composition range the mixtures exhibit two nematic phases with distinct birefringence and dielectric features. Birefringence measurements are used to estimate the temperature dependence of the tilt between the axis defining the nanoscale helical modulation of the low temperature nematic phase with the (local) direction of the maximal alignment of the cyanobiphenyl units. Planar as well as magnetically and/or electrically aligned samples are used to measure the perpendicular and parallel components of the dielectric permittivity in both nematic phases. A self-consistent molecular field theory that takes into account flexibility and symmetry of the constituent mesogens is introduced for the calculation of order parameters and intra-molecular orientational dipolar correlations of the flexible dimers as a function of temperature/concentration. Utilising the tilt angle, as calculated from the birefringence measurements, and the predictions of the molecular theory, dielectric permittivity is modelled in the framework of the anisotropic version of the Kirkwood-Fröhlich theory. Using the inter-molecular Kirkwood correlation factors as adjustable parameters, excellent agreement between theory and permittivity measurements across the whole temperature range and composition of the mixtures is obtained. The importance of the orientational, intra- and inter-molecular, dipolar correlations, their relative impact on the static dielectric properties, as well as their connection with the local structure of the nematic phases of bent-shaped bimesogens, is discussed.

Clinical Impact of the Early Use of Monoclonal Antibody LY-CoV555 (Bamlanivimab) on Mortality and Hospitalization Among Elderly Nursing Home Patients: A Multicenter Retrospective Study.

Importance Coronavirus disease 2019 (COVID-19) outbreaks are frequent occurrences in nursing homes and long-term care facilities (LTCFs), resulting in subsequent hospitalization and death. Rationale Virus-neutralizing monoclonal antibodies demonstrate a significant decrease in both viral load and hospital transfer rate among patients with mild-to-moderate COVID-19 infection. Objective To assess the clinical outcomes of COVID-19 patients with mild-to-moderate symptoms in LTCFs who received LY-CoV555 as compared to those who did not receive this treatment. Design Retrospective case-control study and logistic regression analysis. Setting LTCFs in New York. Participants Two-hundred forty-six (246) LTCF patients diagnosed with mild-to-moderate COVID-19 infection with positive COVID-19 polymerase chain reaction (PCR) from November 15, 2020, to January 31, 2021. Methods Two-hundred forty-six (246) COVID-19 patients were identified from electronic medical records, out of which 160 cases were exposed to LY-CoV555 treatment (700 mg single dose, intravenous infusion). Eighty-six (86) patients were unexposed controls who did not receive monoclonal antibodies, LY-CoV555. Outcome We assessed the odds of death and hospitalization of exposed cases as compared to unexposed controls. Using logistic regression analysis, we also assessed the risk factors associated with these outcomes in the entire sample population. Results The mean age of the entire sample was 82.4 years. Fifty-two percent (52%) of patients (n = 129) were female and 48% (n = 117) were male. The mean ages of the exposed group and the unexposed group were 81 years and 84 years, respectively. At the end of the study, 92% (148/160) of the exposed group were alive or not transferred to the hospital as compared to 79% (68/86) patients of the unexposed group (OR 3.23, 95% CI: (1.48, 7.31), p-value = 0.0032). Three percent (3%; 5/160) of patients died in the exposed group compared to 10% (9/86) of patients who died in the unexposed group (OR = 0.25, 95% CI: (0.1, 0.85), p-value = 0.0257). Four point thirty-seven percent (4.37%; 7/160) of patients in the exposed group and 10.46% (9/86) of patients in the unexposed group were transferred to the hospital (OR = 0.35, 95% CI: (0.15, 1.08), p-value = 0.0793). Conclusion Early treatment with monoclonal antibody LY-CoV555 is associated with decreased mortality among high-risk patients with mild-to-moderate COVID-19 infection in LTCFs. Although not statistically significant, there was a trend towards a lower risk of hospitalization in patients treated with LY-CoV555.

Electrochemically Induced Mesomorphism Switching in a Chlorpromazine Hydrochloride Lyotropic Liquid Crystal.

The discovery of electrochemical switching of the Lα phase of chlorpromazine hydrochloride in water is reported. The phase is characterized using polarizing microscopy, X-ray scattering, rheological measurements, and microelectrode voltammetry. Fast, heterogeneous oxidation of the lyotropic liquid crystal is shown to cause a phase change resulting from the disordering of the structural order in a stepwise process. The underlying molecular dynamics is considered to be a cooperative effect of both increasing electrostatic interactions and an unfolding of the monomers from "butterfly"-shaped in the reduced form to planar in the oxidized form.

Clinical Outcomes of Early Treatment With Doxycycline for 89 High-Risk COVID-19 Patients in Long-Term Care Facilities in New York.

Rationale Due to the cluster and associated comorbidities in residents of long-term care facilities (LTCFs), COVID-19-associated morbidity and mortality are significantly increased. Multiple therapeutic options, including hydroxychloroquine (HCQ) and azithromycin (AZI), were tried initially to treat moderate to severe COVID-19 and high-risk patients in LTCFs, but they were abandoned due to unfavorable reports. As a less toxic option, we initiated treatment with doxycycline (DOXY) very early in the course of illness. DOXY has antiviral, cardioprotective, immunomodulatory, and anti-inflammatory properties, but the efficacy of early intervention with DOXY in high-risk COVID-19 patients in LTCFs is unknown. Objective The goal of this retrospective study is to describe the clinical outcomes of high-risk COVID-19 patients with moderate to severe symptoms in LTCFs after early intervention with DOXY. Design Case-series analysis Setting LTCFs in New York Participants This observational study examines 89 patients who were diagnosed with COVID-19 from March 18 to May 13, 2020. Exposure All patients who were diagnosed with COVID-19 received DOXY and regular standard of care within 12 hours of the onset of symptoms. Additionally, four patients received meropenem, three patients received Zosyn, two patients received linezolid, and two patients received Bactrim DS. Four patients were on chronic ventilator support. No patients received any steroids or any other antiviral or immunomodulatory agents. The majority of the patients received zinc and calcium supplements as well. Main outcomes and measures Assessed measures were patients' characteristics, fever, shortness of breath (SOB), cough, oxygen saturation/pulse oximetry (POX), radiologic improvements, laboratory tests, DOXY side effects, hospital transfers, and death. Results Eighty-nine (89) high-risk patients, who developed a sudden onset of fever, cough, SOB, and hypoxia and were diagnosed with COVID-19, were treated with DOXY (100 mg PO or intravenous (IV) for seven days) and regular standard of care. Eighty-five percent (85%) of patients (n=76) demonstrated clinical recovery that is defined as resolution of fever (average 3.7 days, Coeff = -0.96, p = 0.0001), resolution of SOB (average 4.2 days), and improvement of POX: average 84% before treatment and average 95% after treatment (84.7 ± 7% vs. 95 ± 2.6%, p = 0.0001). Higher pre- and post-treatment POX is associated with lower mortality (oxygen saturation (Spo2) vs. Death, Coeff = -0.01, p = 0.023; post-Spo2 vs. Death, Coeff = -0.05, p = 0.0002). Within 10 days of symptom onset, 3% of patients (n=3) were transferred to hospital due to clinical deterioration and 11% of patients (n=10) died. The result was followed for 30 days from the onset of symptoms in each patient. Conclusion Early treatment with DOXY for high-risk patients with moderate to severe COVID-19 infections in non-hospital settings, such as LTCFs, is associated with early clinical recovery, decreased hospitalization, and decreased mortality.

A Comparison between Kidney Allograft Biopsies Performed by Nephrologists and Surgeons Versus Interventional Radiologists.

INTRODUCTION: Renal biopsy is an integral part of clinical nephrology practice that helps in the diagnosis of various renal diseases. Across the globe, it is performed by nephrologists and/or surgeons under ultrasound guidance. Lately, this novel procedure has been performed more frequently by the interventional radiologist (IR) as compared to nephrologists and surgeons. METHODS: We completed a retrospective review of 378 consecutive renal biopsies performed at our university hospital in the city center of Philadelphia, Pennsylvania, between September 2008 and June 2011 for various indications. Baseline characteristics were comparable except systolic blood pressure (SBP), prothrombin time (PT), and international normalized ratio (INR) which was higher. Hemoglobin was lower in patients who underwent biopsy by the IR compared to those who were biopsied by nephrologists and/or surgeons. RESULTS: The primary outcome showed the average number of glomeruli obtained with each biopsy was significantly lower by nephrology or surgical teams, 9.09 ± 5.17 vs. 19.17 ± 11.11 obtained by the interventional radiology team, p-value <0.0001. The number of cores obtained with each biopsy was significantly lower by nephrologist or surgeon at the bedside, 1.57 ± 1.05 vs. 2.42 ± 1.26, p-value <0.0001. The average number of attempts to obtain one core was 2.00 ± 1.10 vs. 2.60 ± 1.17 by nephrologist and surgeon vs. IR, respectively, p-value <0.0001. CONCLUSION: Our study clearly shows the superior success of renal biopsy by the IR as compared to the nephrology and surgical teams. This calls for more robust training of nephrology fellows and surgery residents to obtain the renal biopsy to prevent the loss of this unique procedure skill by non-radiology clinicians.

Supramolecular organization of liquid-crystal dimers - bis-cyanobiphenyl alkanes on HOPG by scanning tunneling microscopy.

2D supramolecular organization of a series of six cyanobiphenyls bimesogens deposited on highly oriented pyrolytic graphite (HOPG) is studied by scanning tunneling microscopy (STM). The adsorbates are 1,ω-bis(4-cyanobiphenyl-4'-yl)alkanes (CBnCB) with different lengths of their flexible alkyl spacer (containing from 7 to 12 methylene groups). Microscopic investigations at the molecular resolution allow for detailed analysis of the effect of the alkyl spacer length on the type and the extent of the resulting 2D organization. It was demonstrated that bimesogens with shorter spacers (7 and 8 methylene units) organize in a similar manner characterized by the formation of two types of differently ordered monolayers: dense packed, wherein the molecules are oriented in one direction and ordered into parallel rows (layer structure), or less densely packed where they are organized into a chiral windmill-like structure. For derivatives with longer spacers (ranging from 9 to 12 methylene units) the additional effect of parity of carbon atoms in the spacer (even versus odd) is observed. In this range of the spacer lengths even membered bimesogens are also organized in a typical layer structure. However, odd-membered dimers exhibit a much more complex 2D supramolecular organization with a larger unit cell and a helical arrangement of the molecules. Careful comparison of this structure with the 3D structural data derived from the X-ray diffraction investigations of single crystals indicates that for these bimesogens a clear correlation exists between the observed complex 2D supramolecular organization in the monolayer and the organization in one of the crystallographic planes of the 3D nematic twist-bent phase.

Multiple medication (polypharmacy) and chronic kidney disease in patients aged 60 and older: a pharmacoepidemiologic perspective.

BACKGROUND: Few studies have examined whether there was an independent association between multiple medication use and risk of chronic kidney disease (CKD), with adjustment for cardiometabolic factors. In the study, we aimed to examine this association using a nationally representative sample in CKD patients aged 60 and older. METHODS: In the study, subjects aged ⩾60 years (n = 1306) who participated in the 2011-2012 National Health and Nutrition Examination Survey were analyzed cross-sectionally. CKD was defined using the CKD Epidemiology Collaboration (CKD-EPI) equation i.e. estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2). Patients with multiple medications were classified as those having five or more prescription medications per day. All data analysis was performed using SAS 9.3 version. RESULTS: The prevalence of CKD among age group ⩾80 years, age group 70-79 years and age group 60-69 years were 73.26%, 55.76% and 27.03% respectively (p < 0.001). About half of hypertension (HTN) and diabetic patients aged ⩾60 years had CKD. The prevalence of CKD in patients with cardiovascular disease (CVD) was 60.57%. The logistic regression model without adjustment reflects that those on multiple medications (⩾5 medications/day) had 1.53 (1.02-2.31) times as likely (53% increase) to have CKD compared with those on <5 medications/day. After adjustment for age, CVD, HTN and diabetes mellitus (DM), the odds of CKD for multiple medications appeared to have a protective effect, although it did not reach statistical significance. The adjusted odds ratio [95% confidence interval (CI)] was 0.89 (95% CI: 0.60-1.34); it showed an 11% decreased odds of CKD in patients who were taking multiple medications. The adjusted odds ratio for patients with CVD was 1.38 (95% CI: 0.97-1.98), HTN 1.13 (95% CI: 0.80-1.6), DM 1.78 (95% CI: 1.26-2.51) in age group 70-79 years 3.2 (95% CI: 2.1-4.87) and in age ⩾80 years 6.98 (95% CI: 4.02-12.11) compared with age group 60-69 years old, respectively. CONCLUSION: We did not find significant independent association between use of multiple medications and CKD. The switchover of odds for multiple medication suggested a confounding effect of covariates; further prospective studies are required to find the individualized effect of multiple medications on CKD.

Abdominal compartment syndrome and acute kidney injury due to excessive auto-positive end-expiratory pressure.

Abdominal compartment syndrome is an under-recognized cause of acute kidney injury in critically ill patients. We report a case of a patient with severe obstructive lung disease who, while intubated for respiratory failure, developed abdominal compartment syndrome and oliguric acute kidney injury due to air-trapping and excessive auto-positive end-expiratory pressure (auto-PEEP; also known as intrinsic PEEP). When chemical paralysis was initiated and the auto-PEEP resolved, the patient's intra-abdominal hypertension rapidly improved and kidney function recovered immediately. Abdominal compartment syndrome secondary to excessive auto-PEEP appears to be unreported in the literature; however, any process that significantly increases intrathoracic pressure conceivably could cause increased pressure to be transmitted to the abdominal compartment, resulting in organ failure. Patients undergoing mechanical ventilation, which puts them at risk of airflow obstruction and the development of intra-abdominal hypertension, should be evaluated for air-trapping and excessive auto-PEEP.

Five-year (January 2004-December 2008) surveillance on animal bite and rabies vaccine utilization in the Infectious Disease Hospital, Dhaka, Bangladesh.

The magnitude of animal bite and utilization of rabies vaccine was determined at the Infectious Disease Hospital, Dhaka, Bangladesh. From January 2004 to December 2008, 150,068 patients with animal bite visited the hospital, 86.2% and 13.8% of them received nerve tissue and tissue culture vaccine (TCV), respectively. Dog bite was most frequent, found in 90.7% cases. In 794 rabies cases only 24.4% had a history of post-exposure vaccination. Only a negligible number of patients received rabies immunoglobulin (RIG). To prevent further human deaths and economic losses intra-dermal TCV regime and equine RIG should be immediately introduced in Bangladesh.

Chemotherapy-associated renal dysfunction.

The presence of renal dysfunction in a patient receiving chemotherapy can be devastating. Although many patients with cancer have underlying compromised renal function, some chemotherapeutic agents can actually induce renal abnormalities. An understanding of which traditional and newer chemotherapy agents can affect renal function is useful for physicians so that they can monitor patients for renal abnormalities and initiate preventive strategies to minimize renal complications. This Review highlights renal abnormalities associated with current chemotherapy agents and provides suggestions for preventive measures.

Management of diabetes in patients with chronic kidney disease.

Management of patients with diabetes mellitus and chronic kidney disease (CKD) is a challenging task because multiple factors in each condition may impact the other. Glycemic control offers significant benefits in the prevention of diabetic kidney disease (DKD), but other associated morbidities are also important to address. Patients with diabetes with insufficient glycemic and blood pressure control are at a high risk for developing both cardiovascular disease and progression of nephropathy. This article discusses proper screening, identification, and management in the different stages of DKD, with special considerations for dialysis and transplant patients. We also review information on altered metabolism of medications and the appropriate use of diabetic agents, including recommendations for management of glucose control in CKD.

Angiotensin converting enzyme inhibitors maintain polytetrafluroethylene graft patency.

BACKGROUND: A patent vascular access is crucial for hemodialysis patients. Stenosis and thrombosis lead to access failure. Endothelial injury via angiotensin II may mediate a hyperplastic and prothrombotic response. Thus angiotensin II inhibition with angiotensin-converting enzyme inhibitors (ACEI) may prolong vascular access patency. This study determines the impact of ACEI use on access patency in both polytetrafluroethylene (PTFE) grafts and fistulas. METHODS: Demographics, access history and medication use were reviewed in 266 accesses from four dialysis centres. Primary patency, date of surgery to date of first access failure, was determined. Excluded accesses had incomplete history or <30 day patency. Groups divided into ACEI and non-ACEI based on patient use of ACEI during access patency. Statistical methods included: unpaired Student t to compare continuous variables, Chi-square and Fisher's Exact test to compare proportions and evaluate for risk estimation, univariate and multivariate Cox regression to investigate variables associated with duration of access patency. Cox-adjusted survival and Hazard curves were obtained for significant variables. RESULTS: Non-ACEI (PTFE) graft group included more males and older patients; however, when these covariates were adjusted during both univariate and multivariate regression, suggested, only ACEI use was associated with greater access patency duration, 671.7 days (ACEI) vs 460.0 days (non-ACEI), p=0.012. ACEI group had fewer clotting events, 55% versus 71% (non-ACEI) group, p=0.042. ACEI use had little effect on primary patency of the fistula however male gender increased time to fistula failure, p=0.002. CONCLUSIONS: Retrospective evaluation suggests ACEI use in patients with PTFE grafts may prolong and maintain patency. Fistula patency is affected by gender with longer patency noted in males. Further prospective studies are necessary to confirm the role of ACEI in maintaining vascular access patency.

Drug-associated renal dysfunction and injury.

Renal dysfunction and injury secondary to medications are common, and can present as subtle injury and/or overt renal failure. Some drugs perturb renal perfusion and induce loss of filtration capacity. Others directly injure vascular, tubular, glomerular and interstitial cells, such that specific loss of renal function leads to clinical findings, including microangiopathy, Fanconi syndrome, acute tubular necrosis, acute interstitial nephritis, nephrotic syndrome, obstruction, nephrogenic diabetes insipidus, electrolyte abnormalities and chronic renal failure. Understanding the mechanisms involved, and recognizing the clinical presentations of renal dysfunction arising from use of commonly prescribed medications, are important if injury is to be detected early and prevented. This article reviews the clinical features and basic processes underlying renal injury related to the use of common drugs.