Sub-ppm Nanomechanical Absorption Spectroscopy of Silicon Nitride.

Material absorption is a key limitation in nanophotonic systems; however, its characterization is often obscured by scattering and diffraction. Here we show that nanomechanical frequency spectroscopy can be used to characterize material absorption at the parts per million level and use it to characterize the extinction coefficient κ of stoichiometric silicon nitride (Si3N4). Specifically, we track the frequency shift of a high-Q Si3N4 trampoline in response to laser photothermal heating and infer κ from a model including stress relaxation and both conductive and radiative heat transfer. A key insight is the presence of two thermalization time scales: rapid radiative cooling of the Si3N4 film and slow parasitic heating of the Si chip. We infer κ ∼ 0.1-1 ppm for Si3N4 in the 532-1550 nm wavelength range, matching bounds set by waveguide resonators. Our approach is applicable to diverse photonic materials and may offer new insights into their potential.

Towards cavity-free ground-state cooling of an acoustic-frequency silicon nitride membrane.

We demonstrate feedback cooling of a millimeter-scale, 40 kHz SiN membrane from room temperature to 5 mK (3000 phonons) using a Michelson interferometer, and discuss the challenges to ground-state cooling without an optical cavity. This advance appears within reach of current membrane technology, positioning it as a compelling alternative to levitated systems for quantum sensing and fundamental weak force measurements.

Association between potentially inappropriate medications prescription and health-related quality of life among US older adults.

BACKGROUND: Potentially inappropriate medications (PIMs) are associated with worse health outcomes among older adults. Our objective was to examine the association between PIM prescription and health-related quality of life (HRQoL) among older adults in the United States using nationally representative data. METHODS: This was a retrospective study utilizing 2011-2015 Medical Expenditure Panel Survey (MEPS) data. Community dwelling US adults aged 65 years or older were included. A qualified definition operationalized from the 2019 American Geriatrics Society Beers Criteria® was used to define exposure to PIMs during the study period. The Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) were used to measure HRQoL. Survey-weighted linear regression models were constructed to investigate the association between PIM exposure and participants' PCS and MCS scores. Analyses were stratified across three age cohorts (65-74, 75-85, and ≥85 years). RESULTS: Unadjusted analysis showed poorer scores in the PIM exposed group for both PCS and MCS (all p < 0.001). PIM exposure was associated with poorer PCS scores across all age groups with those aged 65-74 years (adjusted regression coefficient = -1.60 [95% CI = -2.27, -0.93; p < 0.001]), those 75-84 years (adjusted regression coefficient: -1.49 [95% CI = -2.45, -0.53; p = 0.003]), and those 85 years and older (adjusted regression coefficient = -1.65 [95% CI = -3.03, -0.27; p = 0.02]). PIM exposure was also associated with poorer MCS scores in participants aged 65-74 years (adjusted regression coefficient = -0.69 [95% CI = -1.16, -0.22; p = 0.004]) and 85 years and older (adjusted regression coefficient = -2.01 [95% CI = -3.25, -0.78; p = 0.002]). CONCLUSIONS: Our results suggest that patients' exposure to PIMs is associated with poorer HRQoL. Further work is needed to assess whether interventions to deprescribe PIMs may help to improve patients' HRQoL.

Impact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study.

The mortality impact of COVID-19 in Africa remains controversial because most countries lack vital registration. We analysed excess mortality in Kilifi Health and Demographic Surveillance System, Kenya, using 9 years of baseline data. SARS-CoV-2 seroprevalence studies suggest most adults here were infected before May 2022. During 5 waves of COVID-19 (April 2020-May 2022) an overall excess mortality of 4.8% (95% PI 1.2%, 9.4%) concealed a significant excess (11.6%, 95% PI 5.9%, 18.9%) among older adults ( ≥ 65 years) and a deficit among children aged 1-14 years (-7.7%, 95% PI -20.9%, 6.9%). The excess mortality rate for January 2020-December 2021, age-standardised to the Kenyan population, was 27.4/100,000 person-years (95% CI 23.2-31.6). In Coastal Kenya, excess mortality during the pandemic was substantially lower than in most high-income countries but the significant excess mortality in older adults emphasizes the value of achieving high vaccine coverage in this risk group.

HIV testing in jails: Comparing strategies to maximize engagement in HIV treatment and prevention.

Despite 15,000 people enter US jails yearly with undiagnosed HIV infection, routine HIV testing is not standard. Maximizing the yield and speed of HIV testing in short-term detention facilities could promote rapid entry or re-entry of people living with HIV (PLWH) into care. The goal of this study was to evaluate the impact of third generation, rapid point-of-care (rPOC) vs. fourth generation, laboratory-based antigen/antibody (LBAg/Ab) testing on the HIV care cascade in a large urban jail during a planned transition. We used aggregate historical data to compare rPOC testing and LBAg/Ab testing in the D.C. Department of Corrections. We examined two time periods, January to August 2019 when rPOC testing was performed, and October 2019 to January 2020 after LBAg/Ab testing began. We calculated monthly rates of HIV tests performed, HIV test results received, HIV test results received among those tested, antiretroviral therapy (ART) initiation, and proportion of PLWH receiving discharge planning prior to release. We then conducted an interrupted time series analysis to assess the differences between testing periods. There were 14,237 entrants during the first time period and 7,569 entrants during the second. Transitioning from rPOC to LBAg/Ab testing increased the rate of test uptake by 38.5% (95% CI: 14.0, 68.3), decreased the rate of test results received among those tested by 13.1% (95% CI: -14.0, -12.1), and increased the combined rate of HIV tests performed and results received by 20.4% (95% CI: 1.5, 42.8). Although the rate of HIV testing was greater under LBAg/Ab, PLWH received results immediately through rPOC testing, which is critically important in short-stay enviroments. Increasing rPOC uptake would increase its value and combined testing may maximize the detection of HIV and receipt of results among persons passing through jails.

Patient Safety Friendly Hospital Initiative: from evidence to action in seven developing country hospitals.

QUALITY PROBLEM: Recent evidence in the level of patient safety from hospitals in six developing countries in the Eastern Mediterranean Region has demonstrated the high prevalence of adverse events, the excessive rate of death and permanent disability and their high preventability. The Patient Safety Friendly Hospital Initiative (PSFHI) has been launched to respond to these challenges. INITIAL ASSESSMENT: The principal approach of the PSFHI has been to develop an assessment manual that has 140 patient safety standards across five domains--leadership and management, patients and public involvement, safe evidence-based clinical practices, safe environment and lifelong learning. CHOICE OF SOLUTION AND IMPLEMENTATION: Ministries of health of seven countries--Egypt, Jordan, Morocco, Pakistan, Sudan, Tunisia and Yemen were asked to nominate one hospital for assessment and then follow-up with an improvement plan. EVALUATION: The standards are divided into critical (20), core (90) and developmental (30). The range of critical standards, the compulsory standards with which a hospital has to comply, achieved by participating hospitals was 8-78%. Overall, in the domain of leadership and management the highest compliance was 47%, for patients and public involvement 25%, for safe evidence-based clinical practice 53%, for safe environment 64% and for lifelong learning 27%. LESSONS LEARNED: This is the first systematic multi-country initiative in the Eastern Mediterranean Region, which provides compelling evidence that assessment of patient safety standards is feasible and applicable in resource-poor settings and there are significant opportunities for improving the level of patient safety in these hospitals.

Identification of two integral glycosomal membrane proteins in Trypanosoma brucei.

Glycosomal membranes of bloodstream form Trypanosoma brucei were purified to apparent homogeneity by sodium carbonate treatment and found to contain two major integral membrane proteins of 26 kDa (band 10) and 24 kDa (band 11). The procyclic-form glycosomal membranes isolated by the same procedure also resulted in a homogeneous preparation, but each piece of membrane thus purified was associated with an electron-dense granule. Procyclic membranes also contained primarily bands 10 and 11. These two proteins were selectively reduced by protease treatment of intact glycosomes, suggesting surface exposed domain(s) of the two proteins accessible to proteolytic digestion. They and band 8 protein also vanished in glycosomal lysates by apparent proteolysis, implying the presence of a specific protease which degrades the integral membrane proteins upon the loss of membrane integrity. The two proteins, hydrophobic in nature and apparently unglycosylated, have no known biological functions, but their possible involvement in translocating precursor proteins from the cytoplasm into the glycosome of T. brucei is postulated.

Absence of substrate channeling in the glycosome of Trypanosoma brucei.

Glycolytic enzymes in the purified glycosomes of Trypanosoma brucei brucei bloodstream forms were crosslinked to form a large protein complex by the bifunctional reagent dimethyl suberimidate [Aman, R.A., Kenyon, G.L. and Wang, C.C. (1985) J. Biol. Chem. 260, 6966-6973]. The crosslinked enzyme complex was found capable of catalyzing the chain reactions leading from glucose to the formation of alpha-glycerophosphate in the presence of ATP and NADH. To determine whether the crosslinked enzyme complex exhibits multiple substrate channelings, these chain reactions were investigated in the crosslinked complex as well as in a preparation of solubilized native glycosomes. When glucose was present at a relatively high concentration (20 mM), production of alpha-glycerophosphate by the crosslinked complex had no apparent lag phase whereas the free enzyme mixture did. However, when the glucose level was lower (0.5-5.0 mM) the difference between the two enzyme preparations disappeared, a lag phase was found in both cases. Formation of sugar phosphates from radiolabeled glucose, followed by high performance liquid chromatographic analysis, showed no significant difference in the diluting powers of exogenous, unlabeled sugar phosphates added to the crosslinked complex or free enzymes. Exogenous fructose 1,6-diphosphatase demonstrated the same effectiveness in disrupting the chain reactions catalyzed by the crosslinked complex and the free enzyme mixture. In situ generation of 2-deoxyglucose-6-phosphate from 2-deoxyglucose and ATP was observed in the crosslinked complex, but the product had no amplified inhibitory effect on the phosphoglucose isomerase activity in the complex. All results suggest an absence of substrate channelings among the glycolytic enzymes in the glycosome of T. b. brucei bloodstream form.

An improved purification of glycosomes from the procyclic trypomastigotes of Trypanosoma brucei.

The glycosomes of in vitro grown procyclic trypomastigote forms of Trypanosoma brucei were purified by three different procedures and the results compared by electron microscopy, enzyme assays and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Centrifugation on a self-forming Percoll gradient followed by a sucrose gradient centrifugation resulted in the least enriched glycosomal preparation. Centrifugation on a pre-formed Nycodenz gradient gave an improved preparation but the most homogeneous preparation of intact glycosomes was obtained after centrifugation on two successive sucrose gradients. Glycosomes purified by both the Nycodenz and double sucrose gradient procedures appeared larger than in situ glycosomes presumably due to an osmotic effect resulting from disruption of the granular matrix of the organelles. Nevertheless, there appears to be no loss of cisternal contents due to the swelling of the organelles. The glycosomes of the bloodstream form trypomastigotes purified by the same procedures show, however, no sign of swelling. A comparison of glycosomes purified from procyclic trypomastigotes and bloodstream form trypomastigotes prepared by the same double sucrose procedure demonstrated that in the glycosome of procyclic trypomastigotes: activities of hexokinase, phosphoglucose isomerase, phosphofructose kinase, aldolase and phosphoglycerate kinase and diminished by 80-100%; activities of glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase and glycerol-3-phosphate dehydrogenase remain unchanged or are only slightly reduced; there is an appearance of four major new proteins, among which could be phosphoenol pyruvate carboxykinase and malate dehydrogenase. These observations are in basic agreement with those by Hart et al. (Mol. Biochem. Parasitol. 12, 25-35, 1984).

Inhibition of protein synthesis results in super-induction of procyclin (PARP) RNA levels.

Procyclin is an abundant surface antigen found exclusively on the procyclic forms of African trypanosomes. We are interested in the induction of procyclin gene expression during differentiation from bloodstream forms. We find that increased levels of procyclin RNA are evident as early as 15 min after triggering differentiation. The increase in procyclin RNA levels requires the temperature shift from 37 degrees C to 27 degrees C and is aided by addition of the tricarboxylic acid cycle intermediate cis-aconitate. Maximal induction is observed with a combination of three triggers of differentiation: citrate, cis-aconitate and the temperature shift. Protein synthesis does not appear to be required for induction of procyclin RNA during differentiation. In fact, addition of protein synthesis inhibitors results in super-induction of procyclin RNA levels, even under conditions where no induction is normally observed (i.e., at 37 degrees C in the absence of citrate and cis-aconitate). This super-induction was observed with four different protein synthesis inhibitors that affect different stages of translation. Thus, the accumulation of procyclin transcripts may be under the control of a negative regulator whose effective levels are reduced during differentiation from bloodstream to procyclic forms.

Characterization of a native and recombinant Schistosoma haematobium serine protease inhibitor gene product.

Immunologic screening of a Schistosoma haematobium cDNA library with species-specific human antisera identified a clone whose predicted amino acid sequence encodes a member of the serine protease inhibitor (serpin) gene family. This cDNA consists of 1397 bp with a single open reading frame that can encode a 409-amino acid protein of 46,261 Da. The native antigen is a 54-58-kDa glycoprotein and is located on the surface of adult worms. Sequence comparison with other serpins predicts the amino acid Phe at the putative reactive center of the protein. Phenylalanine is also found at the corresponding site of a vaccinia serpin that may contribute to the hemorrhagic phenotype of some strains of cowpox virus. Though the human parasites S. haematobium and Schistosoma mansoni demonstrate a close antigenic relationship, the S. haematobium serpin gene product demonstrates marked species-specific immunogenicity. By Northern blot hybridization, however, both species express a 1700-nucleotide mRNA that hybridizes with the S. haematobium serpin cDNA. The intensity of cross hybridization for the S. mansoni mRNA is 10-fold lower than that for S. haematobium. Southern blots of genomic DNA and gene titration experiments indicate that the S. haematobium gene is present in approximately 4-5 copies per haploid genome.

Efficacy of double gloving technique in major and minor oral surgical procedures: A prospective study.

BACKGROUND: A prospective analysis was carried out over a 1-year period to assess gloves used during 100 major and 100 minor oral surgical procedures to test for efficacy of double gloving in oral surgical procedures. PURPOSE: The purpose of this study was to assess the efficacy of double gloving technique in preventing cross infection in both major and minor oral surgical procedures. MATERIALS AND METHODS: Gloves used during 100 major and 100 minor oral surgical procedures were analyzed to check for glove perforations and skin punctures. 100 sterile gloves were tested as control. STATISTICAL ANALYSIS USED: Chi-square test was used to determine whether there was any difference between the expected and observed values in various categories. RESULTS: A higher number of glove perforations was seen in minor oral surgical procedures compared with major surgeries, dominant hand compared with the nondominant, outer gloves compared with the inner, in procedures which took a longer duration of time to complete, in procedures involving wiring and in the index finger followed by the thumb and the palm. CONCLUSION: Double gloving technique using sterile gloves can be used as an effective means of infection control for all major and minor surgical procedures, especially high-risk procedures involving patients who maybe suffering from or carriers of blood-borne infections.

Effects of cooling and rewarming on the meiotic spindle and chromosomes of in vitro-matured bovine oocytes.

The purpose of this study was to evaluate effects of cooling and rewarming on the meiotic spindle apparatus of bovine oocytes. In experiment 1, in vitro-matured bovine oocytes were either maintained at 39 degrees C or cooled abruptly to 4 degrees C or approximately 25 degrees C. Immunohistochemical and DNA staining for visualization of microtubules and chromosomes, respectively, revealed an anastral, barrel-shaped spindle in bovine oocytes. Exposure to 4 degrees C for 10-20 min caused complete disappearance of the spindle. Some chromosome dispersion occurred after 60 min at 4 degrees C. After exposure to approximately 25 degrees C for 30 min, 90% of oocytes appeared abnormal, having either an abnormal spindle or no spindle. In experiment 2, oocytes cooled to either approximately 25 degrees C or 4 degrees C for 30 min were rewarmed directly or in steps for 15 or 60 min. Spindles did not return to normal in most oocytes regardless of cooling temperature or rewarming scheme. Step-wise rewarming was no more beneficial than direct rewarming. More of the oocytes rewarmed directly contained dispersed chromosomes as time at 39 degrees C increased.

Cross-linking of the enzymes in the glycosome of Trypanosoma brucei.

Glycosomes, the microbody-like organelles containing mainly glycolytic enzymes, were purified from the long slender bloodstream form of Trypanosoma brucei EATRO 110 monomorphic strain by an improved method in which the protozoa were frozen and thawed in 15% glycerol to free, from the plasma membrane, much of the variant surface glycoprotein which used to constitute the major contaminant of our purified glycosomes. The purified glycosomes have 11 major proteins, 6 of which, tentatively identified as phosphofructose kinase, hexokinase, 3-phosphoglycerate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, and alpha-glycerophosphate dehydrogenase, constitute 87% of the total glycosomal protein. The bifunctional cross-linking reagents dimethyl suberimidate and dimethyl-3,3'-dithiobispropionimidate can penetrate the glycosomal membrane and cause extensive cross-linking of all the major glycosomal proteins. The cross-linked complex, insoluble in 0.1% Triton X-100 plus 0.15 M NaCl, contains all the glycosomal enzyme activities with only partial inactivations. All the enzymes are probably cross-linked into one large complex since they all sediment rapidly to the bottom of a 5-20% (v/v) sucrose density gradient. This successful cross-linking with reagents of span lengths of 11-12 A suggests close proximities among the glycosomal enzymes which may explain the extraordinarily high rate of glycolysis in T. brucei. Whether such a close association represents specific spatial arrangement required for genuine substrate channeling among the enzymes will be verified by future kinetic studies of the cross-linked enzyme complex.

The role of compartmentation and glycerol kinase in the synthesis of ATP within the glycosome of Trypanosoma brucei.

Glycosomes, purified from trypomastigote forms of Trypanosoma brucei, contained all the enzymes necessary to convert glucose to alpha-glycerophosphate and 3-phosphoglycerate. The multienzyme reaction which produces 2 alpha-glycerophosphate, 2 ADP, and 2 NAD+ from 1 glucose, 2 ATP, and 2 NADH was studied spectrophotometrically. Intact glycosomes, suspended with 5.6 mM alpha-glycerophosphate and 2 mM ADP, produced ATP inside the glycosomes for glucose phosphorylation at a rate of 0.7 mumol/min/mg protein, so confirming the feasibility of producing ATP from alpha-glycerophosphate and ADP catalyzed by glycosomal glycerol kinase, and coupling this ATP production to the ATP-requiring stages of glycolysis. No evidence was found for direct channeling of the ATP generated by glycerol kinase and either hexokinase or phosphofructose kinase in glycosomal enzyme complexes cross-linked by dimethyl suberimidate treatment of intact glycosomes prior to solubilization of their membrane. Compartmentation of glycolytic intermediates, enzymes, and ATP inside isolated glycosomes was demonstrated by their inaccessibility to exogenous enzymes. We conclude that the compartmentation of the glycosome and the efficient production of ATP in the glycosome from whole cell concentrations of sn-glycerol 3-phosphate and ADP account for the observed whole cell production of equimolar glycerol from glucose with net ATP synthesis by T. brucei under anaerobic conditions.

Corticosteroid use and abuse by medical practitioners for arthritis and related disorders in Pakistan.

A total of 256 consecutive patients attending our out-patient clinic in Islamabad, Pakistan, with complaints of pain in or around the joints were evaluated for use of corticosteroids prescribed by medical practitioners they had seen earlier. The appropriateness of such prescriptions and their consequent effects were assessed. Of the 256 patients, 110 (i.e. 42.5%) were identified as steroid users; some of them were suffering from conditions known to be unresponsive to this form of therapy. One hundred and one of the 256 patients had rheumatoid arthritis and 67% of these had been using steroids, mostly in an irrational manner. The general practitioners and consultants (all non-rheumatologists) were responsible for the majority of steroid prescriptions. Steroid side-effects were observed in 42/110 (38.2%) cases. This prevalent practice in Pakistan is a reflection of the state of affairs in developing countries, and indicates a need for improvement and better regulation of health care in such countries.

Characterization of indigenous fat-tailed and fat-rumped hair sheep in Kenya: diversity in blood proteins.

This paper reports the variation in five blood proteins from five populations of sheep found in Kenya. Blood samples were collected from a total of 309 adult sheep of both sexes in Kwale, Makueni and Kakamega districts for the fat-tailed sheep and in Isiolo district for the fat-rumped hair sheep. Fine-wooled Merino sheep were used in this study as the reference population. Transferrin, esterase-A and esterase-C were polymorphic in all the populations investigated, while albumin was monomorphic for the S allele in the fat-tailed sheep and haemoglobin was fixed for the B allele in the Kwale, Makueni and Isiolo populations. Phylogenies derived from the pairwise genetic distance estimates showed a clear separation between the indigenous sheep populations and the exotic Merino. However, the topology of the former showed rather poor consistency with their morphological classification based on the localization of their fat deposits, namely fat-tailed or fat-rumped hair sheep.