The impact of antenatal and postnatal indoor air pollution or tobacco smoke exposure on lung function at 3 years in an African birth cohort.

BACKGROUND AND OBJECTIVE: Indoor air pollution (IAP) and tobacco smoke exposure (ETS) are global health concerns contributing to the burden of childhood respiratory disease. Studies assessing the effects of IAP and ETS in preschool children are limited. We assessed the impact of antenatal and postnatal IAP and ETS exposure on lung function in a South African birth cohort, the Drakenstein Child Health Study. METHODS: Antenatally enrolled mother-child pairs were followed from birth. Lung function measurements (oscillometry, multiple breath washout and tidal breathing) were performed at 6 weeks and 3 years. Quantitative antenatal and postnatal IAP (particulate matter [PM10 ], volatile organic compounds [VOC]) and ETS exposures were measured. Linear regression models explored the effects of antenatal and postnatal exposures on lung function at 3 years. RESULTS: Five hundred eighty-four children had successful lung function testing, mean (SD) age of 37.3 (0.7) months. Exposure to antenatal PM10 was associated with a decreased lung clearance index (p < 0.01) and postnatally an increase in the difference between resistance at end expiration (ReE) and inspiration (p = 0.05) and decrease in tidal volume (p = 0.06). Exposure to antenatal VOC was associated with an increase in functional residual capacity (p = 0.04) and a decrease in time of expiration over total breath time (tE /tTOT ) (p = 0.03) and postnatally an increase in respiratory rate (p = 0.05). High ETS exposure postnatally was associated with an increase in ReE (p = 0.03). CONCLUSION: Antenatal and postnatal IAP and ETS exposures were associated with impairment in lung function at 3 years. Strengthened efforts to reduce IAP and ETS exposure are needed.

Position statement for adult and paediatric spirometry in South Africa: 2022 update.

Spirometry is required as part of the comprehensive evaluation of both adult and paediatric individuals with suspected or confirmed respiratory diseases and occupational assessments. It is used in the categorisation of impairment, grading of severity, assessment of potential progression and response to interventions. Guidelines for spirometry in South Africa are required to improve the quality, standardisation and usefulness in local respiratory practice. The broad principles of spirometry have remained largely unchanged from previous versions of the South African Spirometry Guidelines; however, minor adjustments have been incorporated from more comprehensive international guidelines, including adoption of the Global Lung Function Initiative 2012 (GLI 2012) spirometry reference equations for the South African population. All equipment should have proof of validation regarding resolution and consistency of the system. Daily calibration must be performed, and equipment quality control processes adhered to. It is important to have standard operating procedures to ensure consistency and quality and, additionally, strict infection control as highlighted during the COVID-19 pandemic. Adequate spirometry relies on a competent, trained operator, accurate equipment, standardised operating procedures, quality control and patient co-operation. All manoeuvres must be performed strictly according to guidelines, and strict quality assurance methods should be in place, including acceptability criteria (for any given effort) and repeatability (between efforts). Results must be categorised and graded according to current guidelines, taking into consideration the indication for the test.

Post-tuberculosis lung health: perspectives from the First International Symposium.

ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1st International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on a toolkit for future PTLD measurement and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.

Maternal HIV and Paediatric Lung Health.

With improved prevention of mother to child transmission of HIV, paediatric HIV disease is less common. However, the number of HIV exposed but uninfected infants is growing. Exposure to maternal HIV impacts infant respiratory health through an increase in known risk factors such as increased preterm birth and low birth weight, suboptimal breastfeeding, increased psychosocial stressors and increased exposure to infective pathogens. Exposure to the HIV virus and altered maternal immune environment result in immunologic changes in the infant that may contribute to respiratory disease risk. HIV exposed infants are at increased risk for severe pneumonia with poorer outcomes compared to unexposed infants. Maternal ART and optimal nutrition, including breastfeeding in high infective disease burden settings, reduce morbidity and mortality in HIV exposed infants and should be prioritized. The impact of exposure to maternal HIV on normal lung growth and risk for chronic respiratory disease is unknown and warrants further investigation.

Lung function in African infants: a pilot study.

BACKGROUND: The burden of childhood respiratory illness is large in low and middle income countries (LMICs). Infant lung function (ILF) testing may provide useful information about lung growth and susceptibility to respiratory disease. However, ILF has not been widely available in LMICs settings where the greatest burden of childhood respiratory disease occurs. AIM: To implement and evaluate a pilot study of ILF testing in a semi-rural setting in South Africa. METHOD: Infant lung function testing was established at a community hospital in South Africa. All measures were done in unsedated infants during sleep. Measurements, made with the infant quietly breathing through a face mask and bacterial filter, included tidal breathing (TBFVL), exhaled nitric oxide (eNO), and sulphur hexafluoride multiple breath washout (MBW) measures using an ultrasonic flow meter and chemoluminescent NO analyzer. RESULTS: Twenty infants, mean age of 7.7 (SD 2.9) weeks were tested; 8 (40%) were Black African and 12 (60%) were mixed race. Five (25%) infants were preterm. There were 19 (95%) successful TBFVL and NO tests and 18 (90%) successful MBW tests. The mean tidal volume was 30.5 ml (SD 5.9), respiratory rate 50.2 breaths per minute (SD 8.7), and eNO 10.4 ppb (SD 7.3). The mean MBW measures were: functional residual capacity 71 ml (SD 13) and the lung clearance index 7.6 (SD 0.5). The intra-subject coefficient of variations (CV) of lung function measures were similar to published normative data for Caucasian European infants. CONCLUSION: In this study we demonstrate that unsedated infant lung function measures of tidal breathing, MBW, and eNO are feasible in a semi-rural African setting with rates comparable to those reported from high income countries.

Cameron lesions in patients with hiatal hernias: prevalence, presentation, and treatment outcome.

Cameron lesions, as defined by erosions and ulcerations at the diaphragmatic hiatus, are found in the setting of gastrointestinal (GI) bleeding in patients with a hiatus hernia (HH). The study aim was to determine the epidemiology and clinical manifestations of Cameron lesions. We performed a retrospective cohort study evaluating consecutive patients undergoing upper endoscopy over a 2-year period. Endoscopy reports were systematically reviewed to determine the presence or absence of Cameron lesions and HH. Inpatient and outpatient records were reviewed to determine prevalence, risk factors, and outcome of medical treatment of Cameron lesions. Of 8260 upper endoscopic examinations, 1306 (20.2%) reported an HH. When categorized by size, 65.6% of HH were small (<3 cm), 23.0% moderate (3-4.9 cm), and 11.4% were large (≥5 cm). Of these, 43 patients (mean age 65.2 years, 49% female) had Cameron lesions, with a prevalence of 3.3% in the presence of HH. Prevalence was highest with large HH (12.8%). On univariate analysis, large HH, frequent non-steroidal anti-inflammatory drug (NSAID) use, GI bleeding (both occult and overt), and nadir hemoglobin level were significantly greater with Cameron lesions compared with HH without Cameron lesions (P ≤ 0.03). Large HH size and NSAID use were identified as independent risk factors for Cameron lesions on multivariate logistic regression analysis. Cameron lesions are more prevalent in the setting of large HH and NSAID use, can be associated with GI bleeding, and can respond to medical management.

Isoniazid preventive therapy in HIV-infected children on antiretroviral therapy: a pilot study.

SETTING: Tuberculosis (TB) is a common cause of mortality and morbidity in children infected with the human immunodeficiency virus (HIV). Data on isoniazid preventive therapy (IPT) efficacy in HIV-infected children receiving antiretroviral therapy (ART) are inconclusive. OBJECTIVE: To assess the efficacy, tolerability and safety of isoniazid (INH) in HIV-infected children on ART. DESIGN: A pilot randomised controlled study of INH was undertaken in HIV-infected children on ART. The primary outcome measure was TB disease or death. RESULTS: A total of 167 children were randomised to receive INH (n = 85) or placebo (n = 82), and followed for a median of 34 months (interquartile range [IQR] 24-52). The median age was 35 months (IQR 15-65). There was one death in a child on INH and none in the placebo group. Eleven (6.6%) cases of TB occurred, 4 (5%) in the INH and 7 (9%) in the placebo group. Among the TB cases, 5 were culture confirmed-2 in the INH group and 3 in the placebo group, all susceptible to INH. Severe adverse events occurred rarely (n = 6; 2%). CONCLUSION: IPT is safe and well tolerated in HIV-infected children on concomitant ART. This study supports the need for a larger study to assess efficacy in HIV-infected children living in TB-endemic areas.

Community-acquired pneumonia in HIV-infected children: a global perspective.

PURPOSE OF REVIEW: Pneumonia is a leading cause of morbidity and death in HIV-infected children. The aim of this study was to review recent advances in the epidemiology, cause, management and prevention of pneumonia in HIV-infected children. RECENT FINDINGS: Pneumonia remains a major cause of death and hospitalization, particularly in sub-Saharan Africa, where the paediatric HIV epidemic is concentrated. HIV-infected children have a higher risk of developing pneumonia and of more severe disease than immunocompetent children. Bacterial pathogens especially Streptococcus pneumoniae, Staphylococcus aureus and Gram-negative bacteria predominate, with rising rates of antimicrobial resistance. Mycobacterium tuberculosis is increasingly reported to cause acute pneumonia. Pneumocystis jirovecii (PCP) remains an important cause of severe pneumonia especially in infants. Viral infections, especially cytomegalovirus-associated pneumonia are common. Polymicrobial infection is increasingly recognized and associated with a worse prognosis. HIV-exposed, negative children have an increased risk of infection with opportunistic pathogens and a poorer outcome than HIV-unexposed children.Increasing access to highly active antiretroviral therapy (HAART) has reduced the incidence of severe pneumonia, eliminated most opportunistic infections and improved outcome. However, pneumonia remains the major cause of morbidity in HIV-infected children taking HAART. Standard case management guidelines are effective at decreasing mortality but require adaptation for high HIV-prevalence areas. Broad-spectrum antibiotics should be used as empiric therapy. Infants or children who are not taking pneumocystis prophylaxis should be treated for PCP.A number of general or specific preventive strategies are effective including early use of HAART at the time of HIV diagnosis, pathogen-specific immunizations, in particular pneumococcal conjugate vaccine, and antibiotic prophylaxis against PCP. SUMMARY: Greater access to preventive and treatment strategies, especially PCP prophylaxis, pneumococcal immunization and HAART, are urgently needed in areas of high childhood HIV prevalence.

SELEX selection of high-affinity oligonucleotides for bacteriophage Ff gene 5 protein.

The Ff gene 5 protein (g5p) is a cooperative ssDNA-binding protein. SELEX was used to identify DNA sequences favorable for g5p binding at physiological ionic strength (200 mM NaCl) and 37 degrees C. Sequences were selected from a library of 58-mers that contained a central variable segment of 26 nucleotides. DNA sequences selected after eight rounds of SELEX were mostly G-rich, with multiple copies of CPuGGPy, TPuGGGPy, and/or PyPuPuGGGPy motifs. This was unexpected, since g5p has higher binding affinities for polypyrimidine than for polypurine sequences. The most recurrent G-rich sequence, named I-3, was found to have g5p-binding properties that were correlated with a structural transition. At 10 mM NaCl, I-3 existed in a single-stranded form that was saturated by g5p in an all-or-none fashion. At 200 mM NaCl, I-3 existed in a structured form that showed CD spectral features of G-quadruplexes. The g5p binding affinity for this structured form of I-3 was >100-fold higher than for the single-stranded form. Moreover, the structured I-3 was saturated by g5p in two steps, the first of which was the formation of an apparent initiation complex consisting of one I-3 strand and about three g5p dimers. Nuclease S1 footprinting and other experiments showed that g5p molecules in the initiation complex at 200 mM NaCl were bound directly to the G-rich variable segment and that the structure of I-3 was retained after saturation by g5p. Thus, G-rich motifs may form structures favorable for initiation of g5p binding and also provide the actual g5p-binding sites.

Ff gene 5 protein has a high binding affinity for single-stranded phosphorothioate DNA.

The gene 5 protein (g5p) of Ff bacteriophages is a well-studied model ssDNA-binding protein that binds cooperatively to the Ff ssDNA genome and single-stranded polynucleotides. Its affinity, K omega (the intrinsic binding constant times a cooperativity factor), can differ by several orders of magnitude for ssDNAs of different nearest-neighbor base compositions [Mou, T. C., Gray, C. W., and Gray, D. M. (1999) Biophys. J. 76, 1537-1551]. We found that the DNA backbone can also dramatically affect the binding affinity. The K omega for binding phosphorothioate-modified S-d(A)(36) was >300-fold higher than for binding unmodified P-d(A)(36) at 0.2 M NaCl. CD titrations showed that g5p bound phosphorothioate-modified oligomers with the same stoichiometry as unmodified oligomers. The CD spectrum of S-d(A)(36) underwent the same qualitative change upon protein binding as did the spectrum of unmodified DNA, and the phosphorothioate-modified DNA appeared to bind in the normal g5p binding site. Oligomers of d(A)(36) with different proportions of phosphorothioate nucleotides had binding affinities and CD perturbations intermediate to those of the fully modified and unmodified sequences. The influence of phosphorothioation on binding affinity was nearly proportional to the extent of the modification, with a small nearest-neighbor dependence. These and other results using d(ACC)(12) oligomers and mutant proteins indicated that the increased binding affinity of g5p for phosphorothioate DNA was not a polyelectrolyte effect and probably was not an effect due to the altered nucleic acid structure, but was more likely a general effect of the properties of the sulfur in the context of the phosphorothioate group.

Evidence from CD spectra and melting temperatures for stable Hoogsteen-paired oligomer duplexes derived from DNA and hybrid triplexes.

The pyr*pur.pyr type of nucleic acid triplex has a purine strand that is Hoogsteen-paired with a parallel pyrimidine strand (pyr*pur pair) and that is Watson-Crick-paired with an antiparallel pyrimidine strand (pur.pyr pair). In most cases, the Watson-Crick pair is more stable than the Hoogsteen pair, although stable formation of DNA Hoogsteen-paired duplexes has been reported. Using oligomer triplexes of repeating d(AG)12 and d(CT)12 or r(CU)12 sequences that were 24 nt long, we found that hybrid RNA*DNA as well as DNA*DNA Hoogsteen-paired strands of triplexes can be more stable than the Watson-Crick-paired strands at low pH. The structures and relative stabilities of these duplexes and triplexes were evaluated by circular dichroism (CD) spectroscopy and UV absorption melting studies of triplexes as a function of pH. The CD contributions of Hoogsteen-paired RNA*DNA and DNA*DNA duplexes were found to dominate the CD spectra of the corresponding pyr*pur.pyr triplexes.

Structural properties of Friedreich's ataxia d(GAA) repeats.

The expansion of trinucleotide repeat sequences is the underlying cause of a growing number of inherited human disorders. To provide correlations between DNA structure and mechanisms of trinucleotide repeat expansion, we investigated potential secondary structures formed from the complementary strands of d(GAA.TTC)n, a sequence whose expansion is associated with Friedreich's ataxia. In 50 mM NaCl, pH 7.5, d(GAA)15 exhibited a cooperative and reversible decrease in large circular dichroism bands at 248 and 272-274 nm over the temperature range of 5-50 degrees C, providing evidence for a base-paired structure at reduced temperatures. Ultraviolet absorbance melting profiles indicated that the melting temperature (Tm) of d(GAA)15 was 40 degrees C. At 5 degrees C, the central portion of d(GAA)15 was hypersensitive to single-strand-specific P1 nuclease degradation and diethyl pyrocarbonate modification, providing evidence for a hairpin conformation. At temperatures between 25 and 35 degrees C in 50 mM NaCl, the triplet repeat region of d(GAA)15 was uniformly resistant to degradation by P1 nuclease, including the central portion of the sequence. Our results indicate that the structure of d(GAA)15 is a hairpin at 5 degrees C, unknown but partially base-paired at 37 degrees C, and an approximately random coil above 65 degrees C.

The binding affinity of Ff gene 5 protein depends on the nearest-neighbor composition of the ssDNA substrate.

The Ff gene 5 protein (g5p) is considered to be a nonspecific single-stranded DNA binding protein, because it binds cooperatively to and saturates the Ff bacteriophage single-stranded DNA genome and other single-stranded polynucleotides. However, the binding affinity Komega (the intrinsic binding constant times a cooperativity factor) differs by over an order of magnitude for binding to single-stranded polynucleotides such as poly[d(A)] and poly[d(C)]. A polynucleotide that is more stacked, like poly[d(A)], binds more weakly than one that is less stacked, like poly[d(C)]. To test the hypothesis that DNA base stacking, a nearest-neighbor property, is involved in the binding affinity of the Ff g5p for different DNA sequences, Komega values were determined as a function of NaCl concentration for binding to six synthetic sequences 48 nucleotides in length: dA48, dC48, d(AAC)16, d(ACC)16, d(AACC)12, and d(AAACC)9A3. The binding affinities of the protein for these sequences were indeed found to be related to the nearest-neighbor compositions of the sequences, rather than to simple base compositions. That is, the g5p binding site, which is spanned by four nucleotides, discriminates among these sequences on the basis of the relative numbers of nearest neighbors (AA, CC, and AC plus CA) in the sequence. The results support the hypothesis that the extent of base stacking/unstacking of the free, nonbound ssDNA plays an important role in the binding affinity of the Ff gene 5 protein.

Decisions and justifications by community mental health providers about hypothetical ethical dilemmas.

OBJECTIVE: Community-based treatment of persons with serious mental illness requires providers to become involved in clients' personal lives to a greater degree than does hospital-based treatment. The study examined attendant ethical dilemmas, especially for staff who lack professional training or work in rural communities. METHODS: A total of 95 staff members from five community mental health centers read 14 vignettes describing ambiguous ethical dilemmas involving professional role boundaries or client confidentiality. Twenty-seven staff members were from rural agencies, and 68 from urban-suburban agencies; 60 were direct care staff, and 35 were supervisory. Participants were asked to make and justify a more conservative or a less conservative decision in response to each dilemma. RESULTS: Years of experience as a mental health provider and previous ethics training correlated positively with staff having experienced more situations similar to those in the vignettes; however, these variables were not related to the decision made or the type of ethical justification for it. When the analysis controlled for experience and previous ethics training, staff made fewer conservative decisions in boundary dilemmas than in confidentiality dilemmas. Compared with nonrural providers, rural providers had experienced more boundary dilemmas and made fewer conservative decisions in response to them. CONCLUSIONS: Boundary problems occur frequently in community-based services, especially in rural settings, and may or may not be handled conservatively. With the expansion of case management and other in vivo services, better understanding of ethical risks and informal practices will help improve services and provide appropriate training and supervision of staff.

Circular dichroism and electron microscopy of a core Y61F mutant of the F1 gene 5 single-stranded DNA-binding protein and theoretical analysis of CD spectra of four Tyr --> Phe substitutions.

A core Y61F mutant of the gene 5 single-stranded DNA-binding protein (g5p) of f1 bacterial virus aggregated when expressed from a plasmid, but, after refolding in vitro, it behaved much like wild-type and may be a stability or folding mutant. Circular dichroism (CD) titrations showed the same cooperative polynucleotide binding modes for Y61F and wild-type g5p. There are n = 4 and n congruent with 2.5 modes for binding to poly[d(A)] at low ionic strengths, but n = 4, n = 3, and n congruent with 2-2.5 modes for binding to fd single-stranded viral DNA (fd ssDNA), where n is the number of nucleotides occluded by each bound g5p monomer in a given mode. Y61F g5p has slightly reduced affinity in the n = 4 mode. Electron microscopy showed that Y61F g5p forms left-handed nucleoprotein superhelices indistinguishable from wild-type. Progression from binding to fd ssDNA in the n = 4 to n = 3 to n congruent with 2-2.5 mode is accompanied by an increase in the number of helical turns, an increase from (7.7 +/- 0.3) to (9.5 +/- 0.3) to ( approximately 10-13) g5p dimers per turn, and a decrease in the number of DNA nucleotides per turn. From CD spectra for four of five possible Y --> F g5p mutants, we infer that the fifth tyrosine, Tyr 56, contributes strongly to the CD. Retention of a strong 229 nm CD band in all mutants indicates that all retain elements of the native structure. Spectra of Y26F, Y34F, and Y61F g5p imply limited mobility of the replacement Phe. Comparison of measured with calculated CD spectra also suggests limited mobility for Tyr 26 and Tyr 34 in g5p in solution, and provides new information that the g5p structure in solution may be dominated by Tyr 41 rotamers differing from that stabilized in the crystal.

Hybrid oligomer duplexes formed with phosphorothioate DNAs: CD spectra and melting temperatures of S-DNA.RNA hybrids are sequence-dependent but consistent with similar heteronomous conformations.

Knowledge of the relative stabilities of S-DNA.RNA hybrids of different sequences is important for choosing RNA targets for hybridization with antisense phosphorothioate oligodeoxyribonucleotides (S-DNAs). It is also important to know how hybrid secondary structure varies with sequence, since different structures could influence thermal stability and the activity of RNase H. Our approach has been to study relatively simple sequences consisting of repeating di-, tri-, and tetranucleotides, which allow the maximum resolution of nearest-neighbor effects. Circular dichroism (CD) spectra and melting temperatures were acquired for 16 hybrid sequences that could be formed by mixing S-DNA and RNA oligomers of 24 nucleotides in length. CD spectra of S-DNA.RNA hybrids were sequence-dependent and were similar to those of analogous unmodified hybrids. From singular value decomposition, the major CD spectral component was like that of the A-conformation. Three nearest-neighbor relationships among the hybrid CD spectra were in as good agreement as are such relationships among spectra of duplex RNAs. Tm values ranged from 44.1 degrees C for S-d(ACT)8. r(AGU)8 to 66.6 degrees C for S-d(CCT)8.r(AGG)8 (in 0.15 M K+, phosphate buffer, pH 7). The S-DNA.RNA hybrids had a sequence-dependence of melting temperatures that was approximately the same as that calculated using published data for normal DNA.RNA hybrids [Sugimoto, N., Nakano, S., Katoh, M., Matsumura, A., Nakamuta, H., Ohmichi, T.,Yoneyama, M., & Sasaki, M. (1995) Biochemistry 34, 11211-11216]. In general, sequence-dependent CD spectra and Tm values of S-DNA.RNA hybrids appear to reflect the unique nearest-neighbor interactions of adjacent base pairs, where the S-DNA and RNA strands are in different, but relatively uniform, conformations.

CD, absorption and thermodynamic analysis of repeating dinucleotide DNA, RNA and hybrid duplexes [d/r(AC)]12.[d/r(GT/U)]12 and the influence of phosphorothioate substitution.

Circular dichroism (CD) spectra and melting temperature (Tm) data for five duplexes containing phosphorothioate linkages were compared with data for four unmodified duplexes to assess the effect of phosphorothioate modification on the structure and stability of DNA. DNA and DNA.RNA duplexes. Nine duplexes were formed by mixing oligomers 24 nt long in 0.15 M K+(phosphate buffer), pH 7.0. Unmodified DNA.DNA and RNA.RNA duplexes were used as reference B-form and A-form structures. The CD spectra of the modified hybrids S-d(AC)12.r(GU)12 and r(AC)12.S-d(GT)12 differed from each other but were essentially the same as the spectra of the respective unmodified hybrids. They were more A-form than B-form in character. CD spectra of duplexes S-d(AC)12.d(GT)12 and d(AC)12.S-d(GT)12 were similar to that of d(AC)12.d(GT)12, except for a reduced long wavelength CD band. Sulfur modifications on both strands of the DNA duplex caused a pronounced effect on its CD spectrum. The order of thermal stability was: RNA.RNA > DNA.DNA > DNA.RNA > S-DNA.DNA > S-DNA. RNA > S-DNA.S-DNA. Phosphorothioation of one strand decreased the melting temperature by 7.8+/-0.6 degrees C, regardless of whether the substitution was in a hybrid or DNA duplex. Thermodynamic parameters were obtained from a multistate analysis of the thermal melting profiles. Interestingly, the destabilizing effect of the phosphorothioate substitution appears to arise from a difference in the entropy upon forming the DNA.DNA duplexes, while the destabilizing effect in the DNA.RNA hybrids appears to come from a difference in enthalpy.