Diastolic dysfunction and clinical outcomes after transcatheter or surgical aortic valve replacement in patients with atypical aortic valve stenosis.

BACKGROUND: Diastolic dysfunction is a predictor of poor outcomes in many cardiovascular conditions. At present, it is unclear whether diastolic dysfunction predicts adverse outcomes in patients with atypical aortic stenosis who undergo aortic valve replacement (AVR). METHODS: Five hundred and twenty-three patients who underwent transcatheter AVR (TAVR) (n = 303) and surgical AVR (SAVR) (n = 220) at a single institution were included in our analysis. Baseline left and right heart invasive hemodynamics were assessed. Baseline transthoracic echocardiograms were reviewed to determine aortic stenosis subtype and parameters of diastolic dysfunction. Aortic stenosis subtype was categorized as typical (normal flow, high-gradient) aortic stenosis, classical, low-flow, low-gradient (cLFLG) aortic stenosis, and paradoxical, low-flow, low-gradient (pLFLG) aortic stenosis. Cox proportional hazard models were utilized to examine the relation between invasive hemodynamic or echocardiographic variables of diastolic dysfunction, aortic stenosis subtype, and all-cause mortality. Propensity-score analysis was performed to study the relation between aortic stenosis subtype and the composite outcome [death/cerebrovascular accident (CVA)]. RESULTS: The median STS risk was 5.3 and 2.5% for TAVR and SAVR patients, respectively. Relative to patients with typical aortic stenosis, patients with atypical (cLFLG and pLFLG) aortic stenosis displayed a significantly higher prevalence of diastolic dysfunction (LVEDP ≥ 20mmHg, PCWP ≥ 20mmHg, echo grade II or III diastolic dysfunction, and echo-PCWP ≥ 20mmHg) and, independently of AVR treatment modality, had a significantly increased risk of death. In propensity-score analysis, patients with atypical aortic stenosis had higher rates of death/CVA than typical aortic stenosis patients, independently of diastolic dysfunction and AVR treatment modality. CONCLUSION: We demonstrate the novel observation that compared with patients with typical aortic stenosis, patients with atypical aortic stenosis have a higher burden of diastolic dysfunction. We corroborate the worse outcomes previously reported in atypical versus typical aortic stenosis and demonstrate, for the first time, that this observation is independent of AVR treatment modality. Furthermore, the presence of diastolic dysfunction does not independently predict outcome in atypical aortic stenosis regardless of treatment type, suggesting that other factors are responsible for adverse clinical outcomes in this higher risk cohort.

Identifying predictive factors and clinical outcomes for high-risk pneumonia among hospitalized pediatric patients with measles in a national tertiary infectious disease hospital from January 2019 to December 2019: A cohort study

Background@#Measles surged worldwide in 2019, which recorded the highest number of cases in the last 23 years. In the Philippines, the peak of the outbreak occurred in January-February 2019.1-3 Pneumonia was the most common severe complication and cause of death of measles. Age, sex, area of residence, immunization history, nutrition status and presence of comorbidities may contribute to the development of high-risk pneumonia in measles patients, affecting clinical outcomes.@*Objective@#This study aimed to determine predictive factors for high-risk pneumonia among hospitalized pediatric patients with measles and clinical outcomes in San Lazaro Hospital from January 2019 to December 2019.@*Methods@#A cohort study was conducted through a review of medical records of pediatric patients with measles admitted at San Lazaro Hospital from January 2019 to December 2019. The following data were extracted: demographic data, immunization history, nutrition status, presence of comorbidities, development of high-risk pneumonia, and clinical outcomes were extracted. Logistic regression was done to determine the factors associated with development of high-risk pneumonia.@*Results@#A total of 530 medical records were reviewed, and 27.9% of these documented severe pneumonia. Most of the patients were less than 5 years of age (84.53%) and were residing in Metro Manila (85.47%). Majority (73.40%) had no vaccination for measles. Chi-square test showed that the variables of age (p=0.001), measles vaccination status (p=0.011), BMI-for-age (p=0.005), weight-for-age (p=0.027), and weight-for-height (p=0.004) were significantly different between those who developed high-risk pneumonia and those who did not. However, in the final multiple logistic regression analysis, only nutritional status was predictive of high-risk pneumonia. Patients with severe wasting were 1.85 times (p=0.010) and patients who were overweight were 4.24 times (p=0.003) more likely to develop high-risk pneumonia. There was also a significant difference in clinical outcomes between those without high-risk and with high-risk pneumonia (p=<0.001). All mortality cases had high-risk pneumonia, were less than 5 years of age, and were unvaccinated.@*Conclusion@#Age, measles vaccination status and nutrition status were the factors identified to be associated with high-risk pneumonia among pediatric patients with measles. Thus, it is important to encourage parents to vaccinate their children against measles and to promote proper nutrition.

The predictive value of chest x-ray and plain chest CT scan as adjunct screening tools for COVID-19 patients in a national tertiary infectious disease hospital from March 1 to November 30, 2020

Background@#COVID-19 is diagnosed via Real Time Reverse Transcription Polymerase Chain Reaction (RT-PCR), with plain chest CT and chest x-ray as adjuncts. In the Philippines, chest x-ray is used as initial screening in assessing potential COVID-19 cases, with plain chest CT scan not routinely used due to higher cost and decreased availability.@*Objective@#This study determined the validity of chest x-ray and plain chest CT as initial screening tools for admitted COVID-19 patients from March 1 to November 30, 2020, at San Lazaro Hospital, comparing these with RT-PCR testing for COVID-19 as initial basis for considering a patient as a possible case of COVID-19.@*Methods@#This was a cross-sectional study of radiographic literature of admitted COVID-19 patients from March 1 to November 30, 2020, at San Lazaro Hospital, all with confirmatory RT-PCR, chest X-rays, and plain chest CTs. Baseline chest x-rays, with initial plain chest CT results, were compared with RT-PCR results. A tally was made, noting radiographic findings on both Chest X-ray and Plain Chest CT most frequently seen among patients with corresponding positive real time RT-PCR results.@*Results@#Chest X-rays done < 2 days from admission revealed involvement of both lungs, with infiltrates located centrally and peripherally, with major predilection for both lower lobes. Plain chest CT was similar, with ground glass opacities as the most common finding, consolidation second. Chest x-ray had a sensitivity of 88.11%, plain chest CT 94.71%. Sensitivity of combined chest x-ray and plain chest CT was 86.78%. Specificity and predictive value were not computed due to non-inclusion of admitted patients with COVID negative RT-PCR swab.@*Conclusion@#Chest X-ray and plain chest CT are useful modalities with high sensitivity in screening patients with fever, cough, and colds on admission. However, initial chest x-ray and plain chest CT scan results do not translate into a prognosis without context of initial diagnostics and management done during confinement.

Mixed-flow design for microfluidic printing of two-component polymer semiconductor systems.

The rational creation of two-component conjugated polymer systems with high levels of phase purity in each component is challenging but crucial for realizing printed soft-matter electronics. Here, we report a mixed-flow microfluidic printing (MFMP) approach for two-component π-polymer systems that significantly elevates phase purity in bulk-heterojunction solar cells and thin-film transistors. MFMP integrates laminar and extensional flows using a specially microstructured shear blade, designed with fluid flow simulation tools to tune the flow patterns and induce shear, stretch, and pushout effects. This optimizes polymer conformation and semiconducting blend order as assessed by atomic force microscopy (AFM), transmission electron microscopy (TEM), grazing incidence wide-angle X-ray scattering (GIWAXS), resonant soft X-ray scattering (R-SoXS), photovoltaic response, and field effect mobility. For printed all-polymer (poly[(5,6-difluoro-2-octyl-2H-benzotriazole-4,7-diyl)-2,5-thiophenediyl[4,8-bis[5-(2-hexyldecyl)-2-thienyl]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl]-2,5-thiophenediyl]) [J51]:(poly{[N,N'-bis(2-octyldodecyl)naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)}) [N2200]) solar cells, this approach enhances short-circuit currents and fill factors, with power conversion efficiency increasing from 5.20% for conventional blade coating to 7.80% for MFMP. Moreover, the performance of mixed polymer ambipolar [poly(3-hexylthiophene-2,5-diyl) (P3HT):N2200] and semiconducting:insulating polymer unipolar (N2200:polystyrene) transistors is similarly enhanced, underscoring versatility for two-component π-polymer systems. Mixed-flow designs offer modalities for achieving high-performance organic optoelectronics via innovative printing methodologies.

Technical success and long-term outcomes after anomalous right coronary artery stenting with cardiac computed tomography angiography correlation.

INTRODUCTION: Anomalous origin of coronary arteries has been observed in about 0.35-2.10% of the population. Patients with anomalous right coronary artery (ARCA) may present with significant symptoms, arrhythmias or ACS, and at times sudden death. Traditionally, surgical correction has been the recommended treatment. However, these may be technically challenging, and bypass grafting for such anomalies has the potential for graft failure because of competitive flow. We sought to determine the intermediate and long-term outcomes of drug-eluting stent placement for patients with symptomatic ARCA. We also looked at angiographic findings suggestive of interarterial course as confirmed by subsequent computed tomography (CT) findings. METHODS: Between January 2005 and December 2012, we enrolled 11 patients for elective percutaneous coronary intervention (PCI) of ARCA in a single center, prospective, nonrandomized fashion. Patients were followed up in clinic at 1 week, 3 months, 6 months, and 1 year, and then annually or more frequently if needed. All patients underwent a cardiac CT, as well as functional stress testing when needed to assess for recurrence of disease. RESULTS: All 11 of our patients, who presented with significant symptomatic stenosis with an ARCA, were successfully treated with PCI. Mean follow-up duration was 8.5 years. The only two deaths during follow-up were related to noncardiac causes (sepsis), with a mortality rate of 18.2%. Two patients had a positive functional study and on subsequent coronary angiography, one of them had significant in-stent restenosis (target lesion revascularization of 9.1%) and one distal to the stent (target vessel revascularization 9.1%). We found the observation of a "slit-like lesion" on angiography to have a sensitivity of 100% and specificity of 86% for the diagnosis of interarterial course of the anomalous vessel seen on subsequent CT. CONCLUSIONS: Our study results suggest that PCI of ARCA is an effective and low-risk alternative to surgical correction, with good procedural success and long-term outcomes. It can provide symptomatic relief in such patients and may reduce the risk of sudden death in younger patients, without the inherent risks associated with surgical repair.

Community-oriented health care during a COVID-19 epidemic: A consensus statement by the PAFP task force on COVID-19

Initial Planning@#Statement 1: A Community-oriented Health Care Plan that contains tasks and activities related to the community organization, environment, health care and social processes in order to mitigate the effect of the COVID-19 epidemic on the community should be developed. Statement 2: The plan should also include adjustments needed to continue the delivery of other health services i.e. maternal and child health, immunization, treatment of other communicable and non-communicable disease but with strict COVID-19 transmission precautions.@*Adjustment in the Community Organization and Environment@#Statement 3: A local task force should be organized to develop and implement the community health plan. The task force should be recognized and supported by the whole community. Statement 4: A facility in the barangay that can be used for isolation in case that a member will be diagnosed to have mild COVID-19. A hospital facility for referral of high-risk cases should also be identified and an emergency referral and transport plan should be established. Statement 5: All community health workers should wear appropriate personal protective equipment in the process of performing their community health work. Statement 6: Households in the community who have members at high-risk i.e. more than 60 years old, with existing chronic illness or other life-threatening condition should be identified and advised to take extra precautions i.e. personal hygiene, wearing mask and physical distancing. Statement 7: During the declared community quarantine period by the community or higher-level authority, all community members and household should be advised to stay at home, limit celebrations and community gatherings@*Performance of Routine Tasks and Activities@#Statement 8: A community-directed information, education and communication (IEC) plan should be developed and implemented for the following: a) Informing every household in the community on the basic and accurate information about COVID-19 and the community plan. b) Encouraging everyone to practice personal hygiene that includes regular and appropriate hand washing, daily bath, coughing and sneezing etiquette, wearing of mask, minimizing hand contact with eyes, nose and mouth and strict personal use of eating utensils, bath towels, etc. c) Encouraging everyone to clean everyday frequently touched surface like doorknobs, light and appliance control switch, gadgets, armchairs and tabletops. Cleaning agents can be ordinary detergents and water or 70% alcohol. d) Encouraging everyone to report and seek help to the community health worker if a household member is exposed and developed mild symptoms of COVID-19@*What to Do When a Member or Household is Exposed or Diagnosed COVID-19@#Statement 9: If there is a household whose member is exposed to a COVID-19, the person should be encouraged to stay home preferably in a room or area adequate for isolation, wear mask and maintain at least 2 meters physical distance from other family members. Statement 10: Other household members should be advised to watch out and monitor for the appearance of symptoms like fever, colds and cough. If the person is low risk but there is difficulty of breathing or worsening of symptoms or if the person is high risk i.e. elderly or with existing chronic disease and symptoms appear, they encouraged to inform the community health worker and facilitate the necessary referral and transport arrangement to the hospital. Call first before going. Statement 11: If the symptoms are mild, continue home isolation or in the isolation facility identified by the community, take over-thecounter medications like paracetamol for fever, increase water intake and ensure adequate nutrition, sleep and rest. Family members and community health workers are encouraged to provide psychological and social support to isolated patients. Discontinuation of isolation can be done if symptoms resolve within 14-21 days@*Epidemiology and Surveillance@#Statement 12: The municipal or city health office should be provided daily with a situation report of the implementation of communityoriented health care for COVID-19. Situation report should include: a) The number of exposed, number of diagnosed cases, number of mild cases, number of cases referred to the hospital and number of cases recovered or died in the community. b) Brief description of best practices

Family-focused home care plan during a COVID 19 epidemic: A consensus statement by the PAFP task force on COVID 19

Initial Planning@#Statement 1: Develop a Family-focused Care Plan that contains tasks and activities related to the family structure, home environment and processes in order to mitigate the effect of the COVID-19 epidemic@*Adjustment in the Family Structure and Home Environment@#Statement 2: Identify a Family Caregiver who will remind the family to follow and implement the plan. Make sure this person is supported by all the members of the family. Statement 3: Identify a room or area that can be used for isolation in the event that a family member will be exposed to a diagnosed COVID-19 patient. Statement 4: Identify those who are at risk i.e. more than 60 years old, with existing chronic illness or other life-threatening condition and advice to take extra precaution. Statement 5: During the declared community quarantine period, all family members should stay at home, limit family celebrations, avoid home parties with outside guests, cancel travels as much as possible and be ready to have more members staying at home@*Performance of Routine Tasks and Activities @#Statement 6: Practice personal hygiene that includes regular and appropriate hand washing, daily bath, cough and sneezing etiquette, minimize hand contact with eyes, nose and mouth and strict personal use of eating utensils, bath towels, etc. Statement 7: Daily cleaning of frequently touched surface like doorknobs, light and appliance control switch, gadgets, armchairs and tabletops. Cleaning agents can be ordinary detergents and water or 70% alcohol@*What to Do When a Member is Exposed@#Statement 8: Advice an exposed family member to stay home and in the room or area allocated for isolation, wear mask and maintain at least 2 meters physical distance from the other family members. Make sure their clothing, personal belongings and other things that they usually hold is cleaned regularly and not touch by other members. Statement 9: Watch out and monitor for the appearance of symptoms like fever, colds and cough. If the person exposed is low risk and there is difficulty of breathing or worsening of symptoms, consult your family doctor. If the person is high risk i.e. elderly or with exiting chronic disease and symptoms appear, consult your family doctor right away. Call first before going to the clinic or hospital. Statement 10: If the symptoms are mild, continue home quarantine, take over-the-counter medications like paracetamol for fever, increase water intake and ensure adequate nutrition, sleep and rest. Other family members are encouraged to provide psychological and social support to an exposed and isolated member. Statement 11: Symptoms usually resolved within 14 days, after which home quarantine can be discontinued between 14-21 days. If symptoms persist beyond 14 days consult your family doctor for advice

Depressive and Anxiety Symptoms among Pediatric In-Patients with Dengue Fever: A Case-Control Study.

BACKGROUND: Psychiatric symptoms have been reported in adult patients with dengue fever (DF); however, information on pediatric patients remains inadequate. We sought to identify the prevalence and predictors of depressive and anxiety symptoms and identify other psychiatric symptoms among pediatric patients with DF. This case-control study involved pediatric in-patients (n = 225) who had clinical or serologic-confirmed DF and healthy school-based controls (n = 260). Participants completed the Revised Child Anxiety and Depression Scale (RCADS). RESULTS: The prevalence of depressive (13.3%) and anxiety (34.2%) symptoms among pediatric patients with DF was significantly (p < 0.001) higher than that among controls (3.5% and 16.2%, respectively). Multiple linear regression analysis found that age, family history of DF, ≤2 days of hospitalization, myalgia, and arthralgia were predictors of increased depressive and anxiety symptoms among the patients. Further, 26.7% of pediatric patients reported irritability, agitation, visual hallucinations, and aggressiveness. CONCLUSION: Pediatric patients present depressive and anxiety symptoms whose levels were associated with social and clinical factors. However, whether these symptoms are present only during the infection or may still persist after recovery or are brought by children's adverse reactions to hospitalization are unknown, and thus, further studies are needed.

Knowledge, Attitude, and Practices Regarding Dengue Fever among Pediatric and Adult In-Patients in Metro Manila, Philippines.

BACKGROUND: Knowledge, attitude, and practice (KAP) of in-patients with dengue fever (DF) through hospital-based surveillance has not been done. This study aimed to assess and compare the KAP, identify its predictors, correlation, and protective factors among pediatric and adult patients with DF and community-based controls to structure proactive community-wide DF prevention and control programs. METHODS: This case-control study involved clinically or serologically confirmed patients (pediatrics n = 233; adults n = 17) with DF admitted in three public hospitals and community-based controls in Metro Manila, Philippines. A pretested structured KAP questionnaire was administered to participants to assess their KAP. RESULTS: Pediatric and adult patients had significantly lower mean scores in the practice (p < 0.001) domain compared with the pediatric and adult controls. Being in senior high school, having had days in hospital, and rash were predictors of KAP among pediatric patients. Knowledge and attitude of patients with DF did not correlate with their practices against DF. Use of mosquito-eating fish, screen windows, and dengue vaccine were protective factors against DF. CONCLUSION: The study highlights the importance of behavioral change for knowledge and attitude to have significant effect to practices against DF. Thus, we recommend two comprehensive health programs, Communication for Behavioral Impact (COMBI) and Health Belief Model (HBM).

Photovoltaic Blend Microstructure for High Efficiency Post-Fullerene Solar Cells. To Tilt or Not To Tilt?

Achieving efficient polymer solar cells (PSCs) requires a structurally optimal donor-acceptor heterojunction morphology. Here we report the combined experimental and theoretical characterization of a benzodithiophene-benzothiadiazole donor polymer series (PBTZF4-R; R = alkyl substituent) blended with the non-fullerene acceptor ITIC-Th and analyze the effects of substituent dimensions on blend morphology, charge transport, carrier dynamics, and PSC metrics. Varying substituent dimensions has a pronounced effect on the blend morphology with a direct link between domain purity, to some extent domain dimensions, and charge generation and collection. The polymer with the smallest alkyl substituent yields the highest PSC power conversion efficiency (PCE, 11%), reflecting relatively small, high-purity domains and possibly benefiting from "matched" donor polymer-small molecule acceptor orientations. The distinctive morphologies arising from the substituents are investigated using molecular dynamics (MD) simulations which reveal that substituent dimensions dictate a well-defined set of polymer conformations, in turn driving chain aggregation and, ultimately, the various film morphologies and mixing with acceptor small molecules. A straightforward energetic parameter explains the experimental polymer domain morphological trends, hence PCE, and suggests strategies for substituent selection to optimize PSC materials morphologies.

Fluorination Effects on Indacenodithienothiophene Acceptor Packing and Electronic Structure, End-Group Redistribution, and Solar Cell Photovoltaic Response.

Indacenodithienothiophene (IDTT)-based postfullerene electron acceptors, such as ITIC (2,2'-[[6,6,12,12-tetrakis(4-hexylphenyl)-6,12-dihydrodithieno[2,3- d:2',3'- d']-s-indaceno[1,2- b:5,6- b']dithiophene-2,8-diyl]-bis[methylidyne(3-oxo-1 H-indene-2,1(3 H)-diylidene)]]bis[propanedinitrile]), have become synonymous with high power conversion efficiencies (PCEs) in bulk heterojunction (BHJ) polymer solar cells (PSCs). Here we systematically investigate the influence of end-group fluorination density and positioning on the physicochemical properties, single-crystal packing, end-group redistribution propensity, and BHJ photovoltaic performance of a series of ITIC variants, ITIC- nF ( n = 0, 2, 3, 4, and 6). Increasing n from 0 → 6 contracts the optical bandgap, but only marginally lowers the LUMO for n > 4. This yields enhanced photovoltaic short-circuit current density and good open-circuit voltage, so that ITIC-6F achieves the highest PCE of the series, approaching 12% in blends with the PBDB-TF donor polymer. Single-crystal diffraction reveals that the ITIC- nF molecules cofacially interleave with ITIC-6F having the shortest π-π distance of 3.28 Å. This feature together with ZINDO-level computed intermolecular electronic coupling integrals as high as 57 meV, and B3LYP/DZP-level reorganization energies as low as 147 meV, rival or surpass the corresponding values for fullerenes, ITIC-0F, and ITIC-4F, and track a positive correlation between the ITIC- nF space-charge limited electron mobility and n. Finally, a heretofore unrecognized solution-phase redistribution process between the 2-(3-oxo-indan-1-ylidene)-malononitrile-derived end-groups (EGs) of IDTT-based NFAs, i.e., EG1-IDTT-EG1 + EG2-IDTT-EG2 ⇌ 2 EG1-IDTT-EG2, with implications for the entire ITIC PSC field, is identified and mechanistically characterized, and the effects on PSC performance are assessed.

All-Polymer Solar Cells: Recent Progress, Challenges, and Prospects.

For over two decades bulk-heterojunction polymer solar cell (BHJ-PSC) research was dominated by donor:acceptor BHJ blends based on polymer donors and fullerene molecular acceptors. This situation has changed recently, with non-fullerene PSCs developing very rapidly. The power conversion efficiencies of non-fullerene PSCs have now reached over 15 %, which is far above the most efficient fullerene-based PSCs. Among the various non-fullerene PSCs, all-polymer solar cells (APSCs) based on polymer donor-polymer acceptor BHJs have attracted growing attention, due to the following attractions: 1) large and tunable light absorption of the polymer donor/polymer acceptor pair; 2) robustness of the BHJ film morphology; 3) compatibility with large scale/large area manufacturing; 4) long-term stability of the cell to external environmental and mechanical stresses. This Minireview highlights the opportunities offered by APSCs, selected polymer families suitable for these devices with optimization to enhance the performance further, and discusses the challenges facing APSC development for commercial applications.

Rabies post-exposure prophylaxis compliance of bite patients: The San Lazaro Hospital Animal B.I.T.E. (Bite Injury Treatment Experience) study

Background@#Post-exposure prophylaxis (PEP) is the most important means of preventing rabies. Intradermal PEP was developed to improve compliance, still, many recipients fail to complete this regimen@*Objective@#To determine the non-monetary factors contributing to non-compliance to PEP among patients in the Animal Bite Treatment Center (ABTC) of San Lazaro Hospital (SLH).@*Methods@#This was an analytical, cross-sectional study. The authors randomly reviewed patient records of SLH-ABTC for one-year period. We characterized the cases according to World Health Organization (WHO) parameters. They determined the day intervals between exposure, first consultation, PEP initiation and follow-up visits. Statistical analyses used were descriptive statistics, χ2 test for independence and binary logistic regression.@*Results@#The authors evaluated 667 records. Patients mostly had Category III exposures (76.91%, 95%CI: 73.92%80.62%). The chances of completing active immunization were more likely among patients exposed to unvaccinated animals (OR=1.85, 95%CI: 1.21-2.84, p=0.004). The chances of receiving passive immunization were higher for injuries on the head/neck regions (OR=8.18, 95%CI: 2.4-27.9, p=0.001). Overall, compliance to PEP was 70.21% and 40.70% for Categories II and III exposures, respectively. PEP compliance was moderately dependent on the exposure category (χ2=38.14, df=1, p<0.001, φ=0.25.@*Conclusion@#Category II exposure patients had better compliance than Category III, since rabies immunoglobulins are not required. The authors did not identify any factors that significantly affected Category II regimen compliance. Among Category III patients, compliance was better if the injuries were bite-inflicted while those who were exposed from “healthy”looking animals were less likely to comply.

Peptide Cotransmitters as Dynamic, Intrinsic Modulators of Network Activity.

Neurons can contain both neuropeptides and "classic" small molecule transmitters. Much progress has been made in studies designed to determine the functional significance of this arrangement in experiments conducted in invertebrates and in the vertebrate autonomic nervous system. In this review article, we describe some of this research. In particular, we review early studies that related peptide release to physiological firing patterns of neurons. Additionally, we discuss more recent experiments informed by this early work that have sought to determine the functional significance of peptide cotransmission in the situation where peptides are released from neurons that are part of (i.e., are intrinsic to) a behavior generating circuit in the CNS. In this situation, peptide release will presumably be tightly coupled to the manner in which a network is activated. For example, data obtained in early studies suggest that peptide release will be potentiated when behavior is executed rapidly and intervals between periods of neural activity are relatively short. Further, early studies demonstrated that when neural activity is maintained, there are progressive changes (e.g., increases) in the amount of peptide that is released (even in the absence of a change in neural activity). This suggests that intrinsic peptidergic modulators in the CNS are likely to exert effects that are manifested dynamically in an activity-dependent manner. This type of modulation is likely to differ markedly from the modulation that occurs when a peptide hormone is present at a relatively fixed concentration in the blood.

Closely packed, low reorganization energy π-extended postfullerene acceptors for efficient polymer solar cells.

New organic semiconductors are essential for developing inexpensive, high-efficiency, solution-processable polymer solar cells (PSCs). PSC photoactive layers are typically fabricated by film-casting a donor polymer and a fullerene acceptor blend, with ensuing solvent evaporation and phase separation creating discrete conduits for photogenerated holes and electrons. Until recently, n-type fullerene acceptors dominated the PSC literature; however, indacenodithienothiophene (IDTT)-based acceptors have recently enabled remarkable PSC performance metrics, for reasons that are not entirely obvious. We report two isomeric IDTT-based acceptors 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-benz-(5, 6)indanone))-5,5,11,11-tetrakis(4-nonylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']di-thiophene (ITN-C9) and 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-benz(6,7)indanone))-5,5,11,11-tetrakis(4-nonylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (ITzN-C9) that shed light on the exceptional IDTT properties vis-à-vis fullerenes. The neat acceptors and blends with fluoropolymer donor poly{[4,8-bis[5-(2- ethylhexyl)-4-fluoro-2-thienyl]benzo[1,2-b:4,5-b']dithiophene2,6-diyl]-alt-[2,5-thiophenediyl[5,7-bis(2-ethylhexyl)-4,8-dioxo4H,8H-benzo[1,2-c:4,5-c']dithiophene-1,3-diyl]]} (PBDB-TF) are investigated by optical spectroscopy, cyclic voltammetry, thermogravimetric analysis, differential scanning calorimetry, single-crystal X-ray diffraction, photovoltaic response, space-charge-limited current transport, atomic force microscopy, grazing incidence wide-angle X-ray scattering, and density functional theory-level quantum chemical analysis. The data reveal that ITN-C9 and ITzN-C9 organize such that the lowest unoccupied molecular orbital-rich end groups have intermolecular π-π distances as close as 3.31(1) Å, with electronic coupling integrals as large as 38 meV, and internal reorganization energies as small as 0.133 eV, comparable to or superior to those in fullerenes. ITN-C9 and ITzN-C9 have broad solar-relevant optical absorption, and, when blended with PBDB-TF, afford devices with power conversion efficiencies near 10%. Performance differences between ITN-C9 and ITzN-C9 are understandable in terms of molecular and electronic structure distinctions via the influences on molecular packing and orientation with respect to the electrode.

Newly Identified Aplysia SPTR-Gene Family-Derived Peptides: Localization and Function.

When individual neurons in a circuit contain multiple neuropeptides, these peptides can target different sets of follower neurons. This endows the circuit with a certain degree of flexibility. Here we identified a novel family of peptides, the Aplysia SPTR-Gene Family-Derived peptides (apSPTR-GF-DPs). We demonstrated apSPTR-GF-DPs, particularly apSPTR-GF-DP2, are expressed in the Aplysia CNS using immunohistochemistry and MALDI-TOF MS. Furthermore, apSPTR-GF-DP2 is present in single projection neurons, e.g., in the cerebral-buccal interneuron-12 (CBI-12). Previous studies have demonstrated that CBI-12 contains two other peptides, FCAP/CP2. In addition, CBI-12 and CP2 promote shortening of the protraction phase of motor programs. Here, we demonstrate that FCAP shortens protraction. Moreover, we show that apSPTR-GF-DP2 also shortens protraction. Surprisingly, apSPTR-GF-DP2 does not increase the excitability of retraction interneuron B64. B64 terminates protraction and is modulated by FCAP/CP2 and CBI-12. Instead, we show that apSPTR-GF-DP2 and CBI-12 increase B20 excitability and B20 activity can shorten protraction. Taken together, these data indicate that different CBI-12 peptides target different sets of pattern-generating interneurons to exert similar modulatory actions. These findings provide the first definitive evidence for SPTR-GF's role in modulation of feeding, and a form of molecular degeneracy by multiple peptide cotransmitters in single identified neurons.

Multifaceted Expression of Peptidergic Modulation in the Feeding System of Aplysia.

Neuropeptides are present in species throughout the animal kingdom and generally exert actions that are distinct from those of small molecule transmitters. It has, therefore, been of interest to define the unique behavioral role of this class of substances. Progress in this regard has been made in experimentally advantageous invertebrate preparations. We focus on one such system, the feeding circuit in the mollusc Aplysia. We review research conducted over several decades that played an important role in establishing that peptide cotransmitters are released under behaviorally relevant conditions. We describe how this was accomplished. For example, we describe techniques developed to purify novel peptides, localize them to identified neurons, and detect endogenous peptide release. We also describe physiological experiments that demonstrated that peptides are bioactive under behaviorally relevant conditions. The feeding system is like others in that peptides exert effects that are both convergent and divergent. Work in the feeding system clearly illustrates how this creates potential for behavioral flexibility. Finally, we discuss experiments that determined physiological consequences of one of the hallmark features of peptidergic modulation, its persistence. Research in the feeding system demonstrated that this persistence can change network state and play an important role in determining network output.