Dental Students’ Perceived Value of Peer‐Mentoring Clinical Leadership Experiences

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153637/1/jddj002203372016803tb06086x.pd

Carbon turnover in the water-soluble protein of the adult human lens.

PurposeHuman eye lenses contain cells that persist from embryonic development. These unique, highly specialized fiber cells located at the core (nucleus) of the lens undergo pseudo-apoptosis to become devoid of cell nuclei and most organelles. Ostensibly lacking in protein transcriptional capabilities, it is currently believed that these nuclear fiber cells owe their extreme longevity to the perseverance of highly stable and densely packed crystallin proteins. Maintaining the structural and functional integrity of lenticular proteins is necessary to sustain cellular transparency and proper vision, yet the means by which the lens actually copes with a lifetime of oxidative stress, seemingly without any capacity for protein turnover and repair, is not completely understood. Although many years of research have been predicated upon the assumption that there is no protein turnover or renewal in nuclear fiber cells, we investigated whether or not different protein fractions possess protein of different ages by using the (14)C bomb pulse.MethodsAdult human lenses were concentrically dissected by gently removing the cell layers in water or shaving to the nucleus with a curved micrometer-controlled blade. The cells were lysed, and the proteins were separated into water-soluble and water-insoluble fractions. The small molecules were removed using 3 kDa spin filters. The (14)C/C was measured in paired protein fractions by accelerator mass spectrometry, and an average age for the material within the sample was assigned using the (14)C bomb pulse.ResultsThe water-insoluble fractions possessed (14)C/C ratios consistent with the age of the cells. In all cases, the water-soluble fractions contained carbon that was younger than the paired water-insoluble fraction.ConclusionsAs the first direct evidence of carbon turnover in protein from adult human nuclear fiber cells, this discovery supports the emerging view of the lens nucleus as a dynamic system capable of maintaining homeostasis in part due to intricate protein transport mechanisms and possibly protein repair. This finding implies that the lens plays an active role in the aversion of age-related nuclear (ARN) cataract

An Optimal Linear Time Algorithm for Quasi-Monotonic Segmentation

Monotonicity is a simple yet significant qualitative characteristic. We consider the problem of segmenting a sequence in up to K segments. We want segments to be as monotonic as possible and to alternate signs. We propose a quality metric for this problem using the l_inf norm, and we present an optimal linear time algorithm based on novel formalism. Moreover, given a precomputation in time O(n log n) consisting of a labeling of all extrema, we compute any optimal segmentation in constant time. We compare experimentally its performance to two piecewise linear segmentation heuristics (top-down and bottom-up). We show that our algorithm is faster and more accurate. Applications include pattern recognition and qualitative modeling.Comment: This is the extended version of our ICDM'05 paper (arXiv:cs/0702142

Examining the Relationship between Urogenital Schistosomiasis and HIV Infection

Urogenital schistosomiasis is a parasitic infection caused by a worm, Schistosoma haematobium, which lives in the bloodstream of infected individuals. It affects at least 112 million people, mostly in sub-Saharan Africa, and has been suggested to be a risk factor for becoming infected with HIV. We reviewed publications in order to examine whether it seems likely that this parasitic infection could be a risk factor for HIV. Evidence from many types of studies supports the hypothesis that urogenital schistosomiasis does increase a person's risk of becoming infected with HIV. Studies also suggest that individuals who have both urogenital schistosomiasis and HIV have a more aggressive HIV infection and can more easily transmit HIV to their sexual partners. Praziquantel is an oral, nontoxic, inexpensive medication that is safe in pregnancy and is recommended for treatment of schistosomiasis. In areas where both infections co-exist, regular administration of praziquantel both to young girls and to sexually-active women may be an important approach to reducing HIV transmission. Our findings support the importance of making praziquantel more available to people who live in areas of the world where both urogenital schistosomiasis and HIV infection are widespread

Traffic of Kv4 K+ channels mediated by KChIP1 is via a novel post-ER vesicular pathway

The traffic of Kv4 K+ channels is regulated by the potassium channel interacting proteins (KChIPs). Kv4.2 expressed alone was not retained within the ER, but reached the Golgi complex. Coexpression of KChIP1 resulted in traffic of the channel to the plasma membrane, and traffic was abolished when mutations were introduced into the EF-hands with channel captured on vesicular structures that colocalized with KChIP1(2–4)-EYFP. The EF-hand mutant had no effect on general exocytic traffic. Traffic of Kv4.2 was coat protein complex I (COPI)–dependent, but KChIP1-containing vesicles were not COPII-coated, and expression of a GTP-loaded Sar1 mutant to block COPII function more effectively inhibited traffic of vesicular stomatitis virus glycoprotein (VSVG) than did KChIP1/Kv4.2 through the secretory pathway. Therefore, KChIP1seems to be targeted to post-ER transport vesicles, different from COPII-coated vesicles and those involved in traffic of VSVG. When expressed in hippocampal neurons, KChIP1 co-distributed with dendritic Golgi outposts; therefore, the KChIP1 pathway could play an important role in local vesicular traffic in neurons

Universal screening of Tanzanian HIV-infected adult inpatients with the serum cryptococcal antigen to improve diagnosis and reduce mortality: an operational study

Cryptococcal meningitis is a leading cause of death among HIV-infected individuals in sub-Saharan Africa. Recent developments include the availability of intravenous fluconazole, cryptococcal antigen assays and new data to support fluconazole pre-emptive treatment. In this study, we describe the impact of screening HIV-positive adult inpatients with serum cryptococcal antigen (CRAG) at a Tanzanian referral hospital. All adults admitted to the medical ward of Bugando Medical Centre are counseled and tested for HIV. In this prospective cohort study, we consecutively enrolled HIV-positive patients admitted between September 2009 and January 2010. All patients were interviewed, examined and screened with serum CRAG. Patients with positive serum CRAG or signs of meningitis underwent lumbar puncture. Patients were managed according to standard World Health Organization treatment guidelines. Discharge diagnoses and in-hospital mortality were recorded.\ud Of 333 HIV-infected adults enrolled in our study, 15 (4.4%) had confirmed cryptococcal meningitis and 10 of these 15 (66%) died. All patients with cryptococcal meningitis had at least two of four classic symptoms and signs of meningitis: fever, headache, neck stiffness and altered mental status. Cryptococcal meningitis accounted for a quarter of all in-hospital deaths. Despite screening of all HIV-positive adult inpatients with the serum CRAG at the time of admission and prompt treatment with high-dose intravenous fluconazole in those with confirmed cryptococcal meningitis, the in-hospital mortality rate remained unacceptably high. Improved strategies for earlier diagnosis and treatment of HIV, implementation of fluconazole pre-emptive treatment for high-risk patients and acquisition of better resources for treatment of cryptococcal meningitis are needed

Quantum Computing in Molecular Magnets

Shor and Grover demonstrated that a quantum computer can outperform any classical computer in factoring numbers and in searching a database by exploiting the parallelism of quantum mechanics. Whereas Shor's algorithm requires both superposition and entanglement of a many-particle system, the superposition of single-particle quantum states is sufficient for Grover's algorithm. Recently, the latter has been successfully implemented using Rydberg atoms. Here we propose an implementation of Grover's algorithm that uses molecular magnets, which are solid-state systems with a large spin; their spin eigenstates make them natural candidates for single-particle systems. We show theoretically that molecular magnets can be used to build dense and efficient memory devices based on the Grover algorithm. In particular, one single crystal can serve as a storage unit of a dynamic random access memory device. Fast electron spin resonance pulses can be used to decode and read out stored numbers of up to 10^5, with access times as short as 10^{-10} seconds. We show that our proposal should be feasible using the molecular magnets Fe8 and Mn12.Comment: 13 pages, 2 figures, PDF, version published in Nature, typos correcte

LPS-TLR4 Signaling to IRF-3/7 and NF-κB Involves the Toll Adapters TRAM and TRIF

Toll–IL-1–resistance (TIR) domain–containing adaptor-inducing IFN-β (TRIF)–related adaptor molecule (TRAM) is the fourth TIR domain–containing adaptor protein to be described that participates in Toll receptor signaling. Like TRIF, TRAM activates interferon regulatory factor (IRF)-3, IRF-7, and NF-κB-dependent signaling pathways. Toll-like receptor (TLR)3 and 4 activate these pathways to induce IFN-α/β, regulated on activation, normal T cell expressed and secreted (RANTES), and γ interferon–inducible protein 10 (IP-10) expression independently of the adaptor protein myeloid differentiation factor 88 (MyD88). Dominant negative and siRNA studies performed here demonstrate that TRIF functions downstream of both the TLR3 (dsRNA) and TLR4 (LPS) signaling pathways, whereas the function of TRAM is restricted to the TLR4 pathway. TRAM interacts with TRIF, MyD88 adaptor–like protein (Mal)/TIRAP, and TLR4 but not with TLR3. These studies suggest that TRIF and TRAM both function in LPS-TLR4 signaling to regulate the MyD88-independent pathway during the innate immune response to LPS

Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian adults: a cross-sectional study.

BACKGROUND: The epidemics of HIV and hypertension are converging in sub-Saharan Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living longer and gaining weight, putting them at greater risk for hypertension and kidney disease. The relationship between hypertension, kidney disease and long-term ART among African adults, though, remains poorly defined. Therefore, we determined the prevalences of hypertension and kidney disease in HIV-infected adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We hypothesized that there would be a higher hypertension prevalence among HIV-infected adults on ART, even after adjusting for age and adiposity. METHODS: In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years old) attending an HIV clinic in Tanzania were enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive, and 3) HIV-infected on ART for >2 years. The main study outcomes were hypertension and kidney disease (both defined by international guidelines). We compared hypertension prevalence between each HIV group versus the control group by Fisher's exact test. Logistic regression was used to determine if differences in hypertension prevalence were fully explained by confounding. RESULTS: Among HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community survey data). HIV-infected adults on ART had a higher prevalence of hypertension (43/150 (28.7%), P = 0.01) and a higher odds of hypertension even after adjustment (odds ratio (OR) = 2.19 (1.18 to 4.05), P = 0.01 in the best model). HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151 (5.3%), P = 0.003) and a lower odds of hypertension after adjustment (OR= 0.35 (0.15 to 0.84), P = 0.02 in the best model). Awareness of hypertension was ≤ 25% among hypertensive adults in all three groups. Kidney disease was common in all three groups (25.6% to 41.3%) and strongly associated with hypertension (P 2 years had two-fold greater odds of hypertension than HIV-negative controls. HIV-infected adults with hypertension were rarely aware of their diagnosis but often have evidence of kidney disease. Intensive hypertension screening and education are needed in HIV-clinics in sub-Saharan Africa. Further studies should determine if chronic, dysregulated inflammation may accelerate hypertension in this population