Ruptured Endometrioma with Hemoperitoneum Requiring Emergency Laparotomy: A Case Report.

Endometrioma is the localization of endometriosis in ovary which often develops as cyst. The condition can be complicated with infection, torsion and rupture leading to significant hemoperitoneum and ascites. We present here a 28-year female P2 L1 presented with the features of acute abdomen and severe anemia referred from other hospital where pain management was done. She had raised Ca-125 level, negative Urine Beta HCG and USG findings of left endometrioma with degenerating subserosal fibroid. The improvement of her general condition with analgesics was misleading however a static hematocrit level despite blood transfusion raised suspicion of ongoing pathology leading to blood loss and diagnostic paracentesis confirmed the hemoperitoneum while awaiting of CT report. She underwent Emergency Laparotomy which revealed hemoperitoneum of 2000ml and right ruptured ovarian endometrioma measuring and left ovarian cyst measuring 6x6 cm was noted. The postoperative period was uneventful. Keywords: Acute abdomen; case report; endometriosis; hemoperitoneum; ruptured endometrioma.

Vaginoplasty with Amnion Graft: Management of Mayer-Rokitansky-Kuster-Hauser Syndrome.

Mayer-Rokitansky-Kuster-Hauser syndrome also known as mullerian agenesis is a rare congenital condition in which there is absence of uterus along with upper vagina. Patient usually presents with primary amenorrhea with or without cyclical lower abdominal pain but have normal secondary sexual characters. Modified McIndoe Vaginoplasty with amnion graft is the commonest surgery performed worldwide. A 23 year old girl with normal secondary sexual characters presented with primary amenorrhea with cyclical lower abdominal pain; on examination blind vagina was present. Vaginoplasty with amnion graft was done and vaginal mould was placed. Vaginal dilatation with Hegar's dilator was done weekly until 6 weeks. She is under regular follow-up at present and advised for regular manual dilation at home. McIndoe Vaginoplasty with amnion graft is a simple yet rewarding procedure especially in low resource countries like ours, with good success rate and with minimal postoperative complications. Keywords: Amnion graft; Mayer-Rokitansky-Kuster-Hauser Syndrome; Modified McIndoe Vaginoplasty; Primary amenorrhea; Secondary sexual characters.

A Computational Study of the Electronic Energy and Charge Transfer Rates and Pathways in the Tetraphenyldibenzoperiflanthene/Fullerene Interfacial Dyad.

The electronic transition rates and pathways underlying interfacial charge separation in tetraphenyldibenzoperiflanthene:fullerene (DBP:C70) blends are investigated computationally. The analysis is based on a polarization-consistent framework employing screened range-separated hybrid functional in a polarizable continuum model to parametrize Fermi's golden rule rate theory. The model considers the possible transitions within the 25 lowest excited states of a DBP:C70 dyad that are accessible by photoexcitation. The different identified pathways contributing to charge carrier generation include electron and hole transfer and backtransfer, exciton transfer, and internal relaxation steps. The larger density of states of C70 appears to explain the previously observed larger efficiency for charge separation through hole transfer mechanism. We also analyze the validity of the high-temperature and short-time semiclassical approximations of the FGR theory, where both overestimated and underestimated Marcus theory based constants can be affected.

Visible light-activatable platinum(IV) prodrugs harnessing CD36 for ovarian cancer therapy.

We hereby engineered photoactivatable Pt(IV) metallodrugs that harness CD36 to target ovarian cancer cells. Pt(IV) compounds mimic the structure of fatty acids and take advantage of CD36 as a "Trojan horse" to gain entry into the cells. We confirmed that CD36-dependent entry occurs using graphite furnace atomic absorption spectroscopy with ovarian cancer cells expressing different levels of CD36 and a CD36 inhibitor, SSO. Once the Pt(IV) metallodrugs enter the cancer cells, they can be activated to form Pt(II) with characteristics of cisplatin under visible light (490 nm) irradiation, promoting photoinduced electron transfer from the attached fluorophore to the metal center. This light-induced activation can increase the cytotoxicity of the Pt(IV) metallodrugs by up to 20 times toward ovarian cancer cells, inducing DNA damage and enabling efficient elimination of drug-resistant cancer cells.

Correlating Interfacial Charge Transfer Rates with Interfacial Molecular Structure in the Tetraphenyldibenzoperiflanthene/C70 Organic Photovoltaic System.

Organic photovoltaics (OPV) is an emerging solar cell technology that offers vast advantages such as low-cost manufacturing, transparency, and solution processability. However, because the performance of OPV devices is still disappointing compared to their inorganic counterparts, better understanding of how controlling the molecular-level morphology can impact performance is needed. To this end, one has to overcome significant challenges that stem from the complexity and heterogeneity of the underlying electronic structure and molecular morphology. In this Letter, we address this challenge in the context of the DBP/C70 OPV system by employing a modular workflow that combines recent advances in electronic structure, molecular dynamics, and rate theory. We show how the wide range of interfacial pairs can be classified into four types of interfacial donor-acceptor geometries and find that the least populated interfacial geometry gives rise to the fastest charge transfer (CT) rates.

Mutually Orthogonal Bioconjugation of Vinyl Nucleosides for RNA Metabolic Labeling.

We report a strategy for the orthogonal conjugation of the vinyl nucleosides, 5-vinyluridine (5-VU) and 2-vinyladenosine (2-VA), via selective reactivity with maleimide and tris(2-carboxyethyl)phosphine (TCEP), respectively. The orthogonality was investigated using density functional theory (DFT) and confirmed by reactions with vinyl nucleosides. Further, these chemistries were used to modify RNA for fluorescent cell imaging. These reactions allow for the expanded use of RNA metabolic labeling to study nascent RNA expression within different RNA populations.

Antibiotic resistance and detection of plasmid mediated colistin resistance mcr-1 gene among Escherichia coli and Klebsiella pneumoniae isolated from clinical samples.

BACKGROUND: The prevalence of antimicrobial resistance (AMR) among Gram-negative bacteria is alarmingly high. Reintroduction of colistin as last resort treatment in the infections caused by drug-resistant Gram-negative bacteria has led to the emergence and spread of colistin resistance. This study was designed to determine the prevalence of drug-resistance among beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae, isolated from the clinical specimens received at a tertiary care centre of Kathmandu, Nepal during the period of March to August, 2019. METHODS: A total of 3216 different clinical samples were processed in the Microbiology laboratory of Kathmandu Model Hospital. Gram-negative isolates (E. coli and K. pneumoniae) were processed for antimicrobial susceptibility test (AST) by using modified Kirby-Bauer disc diffusion method. Drug-resistant isolates were further screened for extended-spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL), carbapenemase and K. pneumoniae carbapenemase (KPC) production tests. All the suspected enzyme producers were processed for phenotypic confirmatory tests. Colistin resistance was determined by minimum inhibitory concentration (MIC) using agar dilution method. Colistin resistant strains were further screened for plasmid-mediated mcr-1 gene using conventional polymerase chain reaction (PCR). RESULTS: Among the total samples processed, 16.4% (529/3216) samples had bacterial growth. A total of 583 bacterial isolates were recovered from 529 clinical samples. Among the total isolates, 78.0% (455/583) isolates were Gram-negative bacteria. The most predominant isolate among Gram-negatives was E. coli (66.4%; 302/455) and K. pneumoniae isolates were 9% (41/455). In AST, colistin, polymyxin B and tigecycline were the most effective antibiotics. The overall prevalence of multidrug-resistance (MDR) among both of the isolates was 58.0% (199/343). In the ESBL testing, 41.1% (n = 141) isolates were confirmed as ESBL-producers. The prevalence of ESBL-producing E. coli was 43% (130/302) whereas that of K. pneumoniae was 26.8% (11/41). Similarly, 12.5% (43/343) of the total isolates, 10.9% (33/302) of E. coli and 24.3% of (10/41) K. pneumoniae were resistant to carbapenem. Among 43 carbapenem resistant isolates, 30.2% (13/43) and 60.5% (26/43) were KPC and MBL-producers respectively. KPC-producers isolates of E. coli and K. pneumoniae were 33.3% (11/33) and 20% (2/10) respectively. Similarly, 63.6% (21/33) of the E. coli and 50% (5/10) of the K. pneumoniae were MBL-producers. In MIC assay, 2.2% (4/179) of E. coli and 10% (2/20) of K. pneumoniae isolates were confirmed as colistin resistant (MIC ≥ 4 µg/ml). Overall, the prevalence of colistin resistance was 3.1% (6/199) and acquisition of mcr-1 was 16.6% (3/18) among the E. coli isolates. CONCLUSION: High prevalence of drug-resistance in our study is indicative of a deteriorating situation of AMR. Moreover, significant prevalence of resistant enzymes in our study reinforces their roles in the emergence of drug resistance. Resistance to last resort drug (colistin) and the isolation of mcr-1 indicate further urgency in infection management. Therefore, extensive surveillance, formulation and implementation of effective policies, augmentation of diagnostic facilities and incorporation of antibiotic stewardship programs can be some remedies to cope with this global crisis.

Cyanide Bridged Platinum-Iron Complexes as Cisplatin Prodrug Systems: Design and Computational Study.

The potential role of cyanide-bridged platinum-iron complexes as an anti-cancer Pt(IV) prodrug is studied. We present design principles of a dual-function prodrug that can upon reduction dissociate and release concurrently six cisplatin units and a ferricyanide anion per prodrug unit. The prodrug molecule is a unique complex of hepta metal centers consisting of a ferricyanide core with six Pt(IV) centers each bonded to the Fe(III) core through a cyano ligand. The functionality of the prodrug is addressed through density functional theory (DFT) calculations.

Screened Range-Separated Hybrid Functional with Polarizable Continuum Model Overcomes Challenges in Describing Triplet Excitations in the Condensed Phase Using TDDFT.

Long range-corrected (LRC) or range-separated hybrid (RSH) functionals where the long-range (LR) limit of electronic interactions is set to the exact exchange have been shown to correct the tendency of traditional density functional theory (DFT) to underestimate the frontier orbital gap. Consequently, the use of such functionals in calculating electronic excited states using linear response based time-dependent DFT (TDDFT) has been successful in correcting the tendency for underestimating the energies of charge transfer states by DFT-based calculations. More recently formulations of functionals that attenuate the LR limit to address condensed-phase effects to polarize the electronic density have been reported. In particular screened RSH (SRSH) combined with polarizable continuum model (PCM) was benchmarked successfully in reproducing the fundamental gap and charge transfer state energies of molecular systems in the condensed phase. Here we use SRSH-PCM to address triplet excited states, and show its success in obtaining correspondence of the low-lying triplet states to the singlet-triplet gap in a similar way that the fundamental orbital gap corresponds to electron removal and addition energies. Importantly, the accuracy of the SRSH-PCM in calculating triplet excitations stands on the polarization consistent framework in addressing the scalar dielectric constant and without affecting the optimal tuning by triplet energies. The prospect of even further improving the SRSH-PCM accuracy in calculating triplet states can be achieved by optimal tuning on the basis of the spin multiplicity gap.

On the Role of the Special Pair in Photosystems as a Charge Transfer Rectifier.

The special pair, a bacteriochlorophyll a (BChl) dimer found at the core of bacterial reaction centers, is known to play a key role in the functionality of photosystems as a precursor to the photosynthesis process. In this paper, we analyze the inherent affinity of the special pair to rectify the intrapair photo-induced charge transfer (CT). In particular, we show that the molecular environment affects the nuclear geometry, resulting in symmetry breaking between the two possible intrapair CT processes. To this end, we study the relationships of the intrapair CT and the molecular geometry with respect to the effective dielectric constant provided by the molecular environment. We identify the special pair structural feature that breaks the symmetry between the two molecules, leading to CT rectification. Excited state energies, oscillator strengths, and electronic coupling values are obtained via time-dependent density functional theory, employing a recently developed framework based on a screened range-separated hybrid functional within a polarizable continuum model (SRSH-PCM). We analyze the rectification capability of the special pair by calculating the CT rates using a first-principles-based Fermi's golden rule approach.

Efficient Charge Generation via Hole Transfer in Dilute Organic Donor-Fullerene Blends.

Efficient organic photovoltaics (OPVs) require broadband charge photogeneration with near-unity quantum yield. This can only be achieved by exploiting all pathways that generate charge. Electron transfer from organic donors to acceptors has been well-studied and is considered the primary path to charge photogeneration in OPVs. In contrast, much less is known about the hole transfer pathway. Here we study charge photogeneration in an archetypal system comprising tetraphenyldibenzoperiflanthene:C70 blends using our recently developed multispectral two-dimensional electronic spectroscopy (M-2DES), supported by time-dependent density functional theory and fully quantum-mechanical Fermi's golden rule rate calculations. Our approach identifies in real time two rapid charge transfer pathways that are confirmed through computational analysis. Surprisingly, we find that both electron and hole transfer occur with comparable rates and efficiencies, facilitated by donor-acceptor electronic interactions. Our results highlight the importance of the hole transfer pathway for optimizing the efficiency of OPV devices employing small-molecule heterojunctions.

Quantitative Accuracy in Calculating Charge Transfer State Energies in Solvated Molecular Complexes Using a Screened Range Separated Hybrid Functional within a Polarized Continuum Model.

A screened-range separated hybrid (SRSH) functional in combination with a polarized continuum model (PCM) was recently implemented within a consistent dielectric polarization treatment. The SRSH-PCM demonstrated excellent agreement of the calculated fundamental orbital gaps with measured energies in the condensed phase. Here we develop a linear response time-dependent DFT (TDDFT) approach to obtain solvated charge transfer state energies. We show that the calculated excited state energies of solvated electron-donor-acceptor complexes are in excellent agreement with measured benchmark values. Specifically we consider donor-acceptor complexes of functionalized anthracenes with tetracyanoethylene in methylene chloride. Our proposed SRSH-PCM calculated energies earn a mean absolute deviation (MAD) from the benchmark values as low as 0.04 eV with optimal tuning in PCM, whereas values based on simpler RSH-PCM, without proper treatment of dielectric screening, are associated with a 0.27 eV MAD.

Fundamental Gaps of Condensed-Phase Organic Semiconductors from Single-Molecule Calculations using Polarization-Consistent Optimally Tuned Screened Range-Separated Hybrid Functionals.

Range-separated hybrid (RSH) functionals have been shown to overcome the tendency of traditional density functional theory to underestimate the fundamental orbital gap. More recently, the screened RSH (SRSH) approach has been developed as a means to extend these functionals to address the effect of the electrostatic environment on the fundamental gap. Here, we report a scheme that combines the SRSH formulation with the polarized continuum model (PCM) within a consistent framework for addressing long-range screened electrostatic interactions, which is further improved by optimal tuning (OT). The quantitative predictive power of the new OT-SRSH-PCM scheme is demonstrated by addressing fundamental gaps in thin films of organic semiconducting materials. This is especially impressive as the approach is based on single molecule calculations. We also discuss the advantages of this approach over alternative schemes combining PCM with RSH. In particular, we show that it avoids the well-documented tendency of standard OT to collapse the range separation parameter when performed within a dielectric continuum.

Excitonic Interactions in Bacteriochlorin Homo-Dyads Enable Charge Transfer: A New Approach to the Artificial Photosynthetic Special Pair.

Excitonically coupled bacteriochlorin (BC) dimers constitute a primary electron donor (special pair) in bacterial photosynthesis and absorbing units in light-harvesting antenna. However, the exact nature of the excited state of these dyads is still not fully understood. Here, we report a detailed spectroscopic and computational investigation of a series of symmetrical bacteriochlorin dimers, where the bacteriochlorins are connected either directly or by a phenylene bridge of variable length. The excited state of these dyads is quenched in high-dielectric solvents, which we attribute to photoinduced charge transfer. The mixing of charge transfer with the excitonic state causes accelerated (within 41 ps) decay of the excited state for the directly linked dyad, which is reduced by orders of magnitude with each additional phenyl ring separating the bacteriochlorins. These results highlight the origins of the excited-state dynamics in symmetric BC dyads and provide a new model for studying the primary processes in photosynthesis and for the development of artificial, biomimetic systems for solar energy conversion.

Enhancing charge mobilities in organic semiconductors by selective fluorination: a design approach based on a quantum mechanical perspective.

Selective fluorination of organic semiconducting molecules is proposed as a means to achieving enhanced hole mobility. Naphthalene is examined here as a root molecular system with fluorination performed at various sites. Our quantum chemical calculations show that selective fluorination can enhance attractive intermolecular interactions while reducing charge trapping. Those observations suggest a design principle whereby fluorination is utilized for achieving high charge mobilities in the crystalline form. The utility of this design principle is demonstrated through an application to perylene, which is an important building block of organic semiconducting materials. We also show that a quantum mechanical perspective of nuclear degrees of freedom is crucial for a reliable description of charge transport.