Schwangerschaft. Fehlgeburt. Geburt. Kindesmord

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Effects of a Brief Case Management Intervention Linking People With HIV to Oral Health Care: Project SMILE

Objectives. Although people with HIV experience significant oral health problems, many consistently identify oral health as an unmet health care need. We conducted a randomized controlled trial to evaluate the impact of a dental case management intervention on dental care use.Methods. We evaluated the intervention according to self-reported dental care use at 6-, 12-, and 18-month follow-ups. Multivariable logistic models with generalized estimating equations were used to assess the effects of the intervention over time.Results. The odds of having a dental care visit were about twice as high in the intervention group as in the standard care group at 6 months (adjusted odds ratio [OR] = 2.52; 95% confidence interval [CI] = 1.58, 4.08) and 12 months (adjusted OR = 1.98; 95% CI = 1.17, 3.35), but the odds were comparable in the 2 groups by 18 months (adjusted OR = 1.07; 95% CI = 0.62, 1.86). Factors significantly associated with having a dental care visit included frequent physician visits and dental care referrals.Conclusions. We demonstrated that a dental case management intervention targeting people with HIV was efficacious but not sustainable over time. Barriers not addressed in the intervention must be considered to sustain its use over time.In the era of antiretroviral therapy, people with HIV are living longer and the treatment of associated medical and oral manifestations of the disease has shifted to a chronic disease model.1 Previous studies have shown that a person living with HIV/AIDS is more likely than a person without the disease to experience oral health problems.2–5 Furthermore, the oral health problems of individuals with HIV can be more severe and difficult to treat than those of the general population and may also contribute to the onset of opportunistic infections.5The oral health complications associated with HIV are well documented,2–6 and oral manifestations are increasingly being recognized as markers for monitoring treatment efficacy and predicting treatment failure.7 Oral manifestations, including Kaposi’s sarcoma, necrotizing ulcerative periodontitis, oral hairy leukoplakia, and candidiasis, may be present in up to 50% of people with HIV and 80% of people diagnosed with AIDS,5,6 and may predict low CD4 counts.8 In addition, individuals living with HIV/AIDS may experience difficulty in maintaining adequate salivary flow, which affects chewing, swallowing, and the ability to take medication.4 Chronic use of highly active antiretroviral therapy can also contribute to diminished salivary flow as well as an increased risk of oral candidiasis and oral hairy leukoplakia.9Throughout the 1990s, a series of study findings highlighted the unmet needs for dental care among people with HIV infection.10–14 This gap in oral health care services was corroborated by findings from the oral health component of the HIV Cost and Services Utilization Study,15 which demonstrated that unmet dental needs were twice as common as unmet medical needs among HIV-positive adults16,17 and led to a national call to action to improve access to oral health care.18 That study also showed that approximately half of people living with HIV had dental insurance, and those without dental insurance had greater unmet needs for dental services.17,19,20Recently published findings suggest that an unmet need still persists. One example is an initiative, funded by the Health Resources and Services Administration, that included 2469 people living with HIV who had not received dental care during the preceding year. Nearly half of these individuals (48%) reported an unmet dental need since their HIV diagnosis, 52% had not seen a dentist in more than 2 years, and 63% rated the health of their teeth and gums as fair or poor.21,22 An earlier investigation involving baseline data from the study presented here showed that oral health problems and symptoms were very prevalent among our study population, with 63% of participants having experienced an oral health impact very often or fairly often in the preceding 4 weeks.23Barriers to dental care use among individuals living with HIV include fear of dental care, HIV-specific stigma, fear of disclosing their HIV status to health care providers, perceived cost barriers, and poor adherence to medical guidance.20,22,24–31 Compounding patient access barriers, dental care providers may be reluctant to treat patients with HIV owing to fears of HIV transmission and associated stigma.32–36Previous research conducted in Florida revealed that more than one third of people with HIV do not discuss oral health with their primary care providers.37 Although clinical guidelines recommend that HIV care providers examine the oral cavity during initial and interim physical examinations of people living with HIV, this still may not be a regular clinical practice.37 To address underuse of oral health care services among individuals with HIV, we evaluated the efficacy of an intervention that linked individuals to dental care. The sample comprised a population of HIV-positive individuals in south Florida who had received HIV primary care but had not received oral health services in the preceding 12 months.     

The potential of myocardial perfusion scintigraphy for risk stratification of asymptomatic patients with type 2 diabetes.

Patients with diabetes, in particular patients with type 2 diabetes, are at a 2- to 4-fold higher risk of cardiovascular mortality compared with their nondiabetic peers. Patients with diabetes are also more likely to have silent ischemia and less likely to survive a myocardial infarction than nondiabetic patients. Recent studies with electron beam computed tomography (EBCT) have shown that subclinical atherosclerosis is common in patients with diabetes, and studies with myocardial perfusion scintigraphy (with single-photon emission computed tomography) or stress echocardiography have demonstrated that between 25% and 50% of asymptomatic diabetic patients have ischemia during exercise or pharmacological stress and that a substantial proportion of these patients go on to develop major cardiovascular events within several years. Clearly, asymptomatic diabetic patients include a subset of individuals at high risk of cardiovascular disease who would benefit from improved risk stratification beyond that possible with risk factor scoring systems alone. Single-photon emission computed tomography, stress echocardiography, and possibly EBCT or multi-slice computed tomography, are emerging as valuable diagnostic tools for identifying asymptomatic diabetic patients who might require early and aggressive intervention to manage their cardiovascular risk.     

Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research

Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item “short” to 65-item “full” SRS scores. Results demonstrated highly overlapping distributions of short and full scores. Both scores separated case from non-case individuals by approximately two standard deviations. ASD prediction was nearly identical for short and full scores (area under the curve values of 0.87, 0.86 respectively). Findings support comparability of shortened and full scores, suggesting opportunities to increase efficiency. Future work should confirm additional psychometric properties of short scores.

     

Mobile hydrogen carbonate acts as proton acceptor in photosynthetic water oxidation

Cyanobacteria, algae, and plants oxidize water to the O₂ we breathe, and consume CO₂ during the synthesis of biomass. Although these vital processes are functionally and structurally well separated in photosynthetic organisms, there is a long-debated role for CO₂/ in water oxidation. Using membrane-inlet mass spectrometry we demonstrate that acts as a mobile proton acceptor that helps to transport the protons produced inside of photosystem II by water oxidation out into the chloroplast’s lumen, resulting in a light-driven production of O₂ and CO₂. Depletion of from the media leads, in the absence of added buffers, to a reversible down-regulation of O₂ production by about 20%. These findings add a previously unidentified component to the regulatory network of oxygenic photosynthesis and conclude the more than 50-y-long quest for the function of CO₂/ in photosynthetic water oxidation.Oxygenic photosynthesis in cyanobacteria, algae, and higher plants leads to the reduction of atmospheric CO₂ to energy-rich carbohydrates. The electrons needed for this process are extracted in a cyclic, light-driven process from water that is split into dioxygen (O₂) and protons. This reaction is catalyzed by a penta-µ-oxo bridged tetra-manganese calcium cluster (Mn₄CaO₅) within the oxygen-evolving complex (OEC) of photosystem II (PSII) (1–4). The possible roles of inorganic carbon, , in this process have been a controversial issue ever since Otto Warburg and Günter Krippahl (5) reported in 1958 that oxygen evolution by PSII strictly depends on CO₂ and therefore has to be based on the photolysis of H₂CO₃ (“Kohlensäure”) and not of water. These first experiments were indirect and, as became apparent later, were wrongly interpreted (6–8). Several research groups followed up on these initial results and identified two possible sites of C_i interaction within PSII (reviewed in refs. 9–12). Functional and spectroscopic studies showed that facilitates the reduction of the secondary plastoquinone electron acceptor (Q_B) of PSII by participating in the protonation of . Binding of (or ) to the nonheme Fe between the quinones Q_A and Q_B was recently confirmed by X-ray crystallography (3, 13, 14). Despite this functional role at the acceptor side, the very tight binding of to this site makes it impossible for the activity of PSII to be affected by changing the C_i level of the medium; instead inhibitors such as formate need to be added to induce the acceptor-side effect (15). Consequently, the water-splitting electron-donor side of PSII has also been studied intensively (for recent reviews, see refs. 11 and 12). Although a tight binding of C_i near the Mn₄CaO₅ cluster is excluded on the basis of X-ray crystallography (3, 14), FTIR spectroscopy (16), and mass spectrometry (17, 18), the possibility that a weakly bound affects the activity of PSII at the donor side remains a viable option (reviewed in refs. 10 and 19).In the present study using higher plant PSII membranes, we specifically evaluate a recently suggested role of weakly bound , namely, that it acts as an acceptor for, and transporter of, protons produced by water splitting in the OEC (20–22).     

13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence,Controversies, Consensus – Opinion of a German Team of Experts (Zurich 2013)

Zusammenfassung

Alle zwei Jahre findet in St. Gallen (Schweiz) die internationale Konsensuskonferenz zur Behandlung des primären Mammakarzinoms statt. Da sich das internationale Panel in St. Gallen aus Experten unterschiedlicher Länder zusammensetzt, spiegelt der Konsensus ein internationales Meinungsbild wider. Vor diesem Hintergrund erscheint es aus deutscher Sicht sinnvoll, die Abstimmungsergebnisse für den Therapiealltag in Deutschland zu konkretisieren. Eine deutsche Arbeitsgruppe mit acht Brustkrebsexperten, von denen zwei Mitglieder des internationalen St. Gallen-Panels sind, hat daher die Abstimmungsergebnisse der St. Gallen-Konsensuskonferenz (2013) für den Klinikalltag in Deutschland kommentiert. Inhaltliche Schwerpunkte der diesjährigen St. Gallen-Konferenz waren operative Fragestellungen der Brust und der Axilla, strahlentherapeutische und systemische Therapieoptionen sowie die klinische Relevanz der Tumorbiologie. Intensiv diskutiert wurde der klinische Einsatz von Multigen-Assays, inkl. ihrer Bedeutung für die individuelle Therapieentscheidung.     

Water oxidation by photosystem II is the primary source of electrons for sustained H2 photoproduction in nutrient-replete green algae

The unicellular green alga Chlamydomonas reinhardtii is capable of photosynthetic H₂ production. H₂ evolution occurs under anaerobic conditions and is difficult to sustain due to 1) competition between [FeFe]-hydrogenase (H₂ase), the key enzyme responsible for H₂ metabolism in algae, and the Calvin–Benson–Bassham (CBB) cycle for photosynthetic reductants and 2) inactivation of H₂ase by O₂ coevolved in photosynthesis. Recently, we achieved sustainable H₂ photoproduction by shifting algae from continuous illumination to a train of short (1 s) light pulses, interrupted by longer (9 s) dark periods. This illumination regime prevents activation of the CBB cycle and redirects photosynthetic electrons to H₂ase. Employing membrane-inlet mass spectrometry and H218O, we now present clear evidence that efficient H₂ photoproduction in pulse-illuminated algae depends primarily on direct water biophotolysis, where water oxidation at the donor side of photosystem II (PSII) provides electrons for the reduction of protons by H₂ase downstream of photosystem I. This occurs exclusively in the absence of CO₂ fixation, while with the activation of the CBB cycle by longer (8 s) light pulses the H₂ photoproduction ceases and instead a slow overall H₂ uptake is observed. We also demonstrate that the loss of PSII activity in DCMU-treated algae or in PSII-deficient mutant cells can be partly compensated for by the indirect (PSII-independent) H₂ photoproduction pathway, but only for a short (<1 h) period. Thus, PSII activity is indispensable for a sustained process, where it is responsible for more than 92% of the final H₂ yield.

Many species of green algae have [FeFe]-hydrogenases (H₂ases) (1) that catalyze the reversible reduction of protons to molecular hydrogen:2H++2e−⇄H2.[1]Since [FeFe]-H₂ases are extremely O₂-sensitive (2), reaction 1 typically proceeds under anoxic conditions. With respect to H₂ metabolism, Chlamydomonas reinhardtii is the most studied alga. This alga possesses two [FeFe]-H₂ases in the chloroplast, HYDA1 and HYDA2 (3, 4). In the light, they accept electrons from photosynthetically reduced ferredoxin (FDX1) (5), while in the dark electrons come from the activity of pyruvate ferredoxin oxidoreductase (PFR1) (6). PFR1 catalyzes the oxidation of pyruvate to acetyl-CoA, and its activity is linked to H₂ase via FDX1 (7). Since [FeFe]-H₂ases interact with the photosynthetic electron transport chain at the level of ferredoxin, they may accept electrons originating both from water oxidation via the photosystem II (PSII)-dependent pathway (“direct water biophotolysis”) and from the degradation of organic substrates via a PSII-independent mechanism (“indirect water biophotolysis” or “indirect pathway”) (8). In the latter case, the reductants are supplied to the plastoquinone (PQ) pool by the type II NADPH dehydrogenase (NDA2), thus bypassing PSII (9, 10).The release of H₂ leads to a loss of metabolic energy. In healthy, actively growing C. reinhardtii cultures, H₂ production is therefore only a temporal phenomenon observed during dark anoxia and upon subsequent onset of illumination (11). In contrast to dark fermentation, H₂ photoproduction is a very efficient process that proceeds for only a short period of time (from a few seconds to a few minutes). Two theories have been developed to explain the short duration. The first is based on the oxygen sensitivity of H₂ases (12, 13). In the light, algae accumulate O₂ that is produced by water oxidation at PSII (14). As a result, H₂ photoproduction may cease over time (14, 15), and the duration of this process is reported to shorten with increased light intensity (16). Because of the negative correlation between the rates of H₂ photoproduction and O₂ evolution, the inhibition of H₂ases by O₂ is frequently quoted as the primary reason for the rapid loss in H₂ photoproduction after the onset of illumination (17).Alternatively, the loss in the H₂ photoproduction efficiency during illumination could be explained by the light-induced induction of competitive pathways, which may drain reducing equivalents away from the [FeFe]-H₂ase enzyme (18, 19). Candidates for this role are the Mehler-like reaction driven by flavodiiron proteins (FDPs) (15, 20, 21) and the Calvin–Benson–Bassham (CBB) cycle (22). Compelling evidence for the competition between these two pathways and H₂ production has been accumulated in recent studies (23–25). As CO₂ fixation provides the strongest sink for photosynthetic reductants, it should play a major role in the cessation of H₂ photoproduction in algae when the CBB cycle is active (19, 22).For preventing competition between the [FeFe]-H₂ases and the CBB cycle, we recently devised a pulse-illumination protocol that allows H₂ production in nutrient-replete algal cultures for up to 3 d (23). To achieve this, we specifically selected the duration of light pulses in the light/dark sequence to avoid activation of the CBB cycle, thus allowing for the redirection of photosynthetic electrons toward the [FeFe]-H₂ases. Typically, a train of 1- to 6-s light pulses interrupted by 9-s dark periods is sufficient for sustained H₂ photoproduction in C. reinhardtii cultures (23, 25). Our protocol thus differs from earlier pulse-illumination approaches that aimed at preventing the accumulation of O₂ in the cultures (26).While we could demonstrate competition of [FeFe]-H₂ase with FDPs (25), the origin of reductants for H₂ photoproduction in the pulse-illuminated algae remained unclear. The relatively high efficiency of the process suggests the involvement of water oxidation by PSII, and consequently the simultaneous production of H₂ and O₂. Although widely proposed in the current literature (8, 24), the presence of the direct water biophotolysis in H₂-producing green algae has not yet been proven by direct experimental data.In the present study, we provide clear evidence for the presence of PSII-dependent oxidation of ¹⁸O-labeled water H218O with concomitant evolution of ¹⁶O₂ and ^16,18O₂ during H₂ photoproduction in the pulse-illuminated green alga C. reinhardtii under anoxic conditions. O₂ evolution is balanced by light-dependent and light-independent respiration that sustains the anoxic condition. We also demonstrate that the loss of PSII activity in algae can be partly compensated by the PSII-independent H₂ photoproduction pathway. Nevertheless, the activity of PSII is indispensable for the sustained process, where it contributes to more than 92% of the final H₂ yield.