Effects of increasing atmospheric CO2 on leaf water δ18O values are small and are attenuated in grasses and amplified in dicotyledonous herbs and legumes when transferred to cellulose δ18O values.

The oxygen isotope composition of cellulose (δ18O values) has been suggested to contain information on stomatal conductance (gs) responses to rising pCO2. The extent by which pCO2 affects leaf water and cellulose δ18O values (δ18OLW and δ18OC) and the isotope processes that determine pCO2 effects on δ18OLW and δ18OC are, however, unknown. We tested the effects of pCO2 on gs, δ18OLW and δ18OC in a glasshouse experiment, where six plant species were grown under pCO2 ranging from 200 to 500 ppm. Increasing pCO2 caused a decline in gs and an increase in δ18OLW, as expected. Importantly, the effects of pCO2 on gs and δ18OLW were small and pCO2 effects on δ18OLW were not directly transferred to δ18OC but were attenuated in grasses and amplified in dicotyledonous herbs and legumes. This is likely because of functional group-specific pCO2 effects on the model parameter pxpex. Our study highlights important uncertainties when using δ18OC as a proxy for gs. Specifically, pCO2-triggered gs effects on δ18OLW and δ18OC are possibly too small to be detected in natural settings and a pCO2 effect on pxpex may render the commonly assumed negative linkage between δ18OC and gs to be incorrect, potentially confounding δ18OC based gs reconstructions.

SP-CHAP, an endolysin with enhanced activity against biofilm pneumococci and nasopharyngeal colonization.

Streptococcus pneumoniae (Spn), a Gram-positive bacterium, is responsible for causing a wide variety of invasive infections. The emergence of multi-drug antibiotic resistance has prompted the search for antimicrobial alternatives. Phage-derived peptidoglycan hydrolases, known as endolysins, are an attractive alternative. In this study, an endolysin active against Spn, designated SP-CHAP, was cloned, produced, purified, biochemically characterized, and evaluated for its antimicrobial properties. Cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domains are widely represented in bacteriophage endolysins but have never previously been reported for pneumococcal endolysins. Here, we characterize the first pneumococcal endolysin with a CHAP catalytic domain. SP-CHAP was antimicrobial against all Spn serovars tested, including capsular and capsule-free pneumococci, and it was found to be more active than the most widely studied pneumococcal endolysin, Cpl-1, while not affecting various oral or nasal commensal organisms tested. SP-CHAP was also effective in eradicating Spn biofilms at concentrations as low as 1.56 µg/mL. In addition, a Spn mouse nasopharyngeal colonization model was employed, which showed that SP-CHAP caused a significant reduction in Spn colony-forming units, even more than Cpl-1. These results indicate that SP-CHAP may represent a promising alternative to combating Spn infections. IMPORTANCE: Considering the high rates of pneumococcal resistance reported for several antibiotics, alternatives are urgently needed. In the present study, we report a Streptococcus pneumoniae-targeting endolysin with even greater activity than Cpl-1, the most characterized pneumococcal endolysin to date. We have employed a combination of biochemical and microbiological assays to assess the stability and lytic potential of SP-CHAP and demonstrate its efficacy on pneumococcal biofilms in vitro and in an in vivo mouse model of colonization. Our findings highlight the therapeutic potential of SP-CHAP as an antibiotic alternative to treat Streptococcus pneumoniae infections.

Current Operative Approaches to the Diseased Gallbladder. Diagnosis and Management Updates for General Surgeons.

Cholecystitis is a common diagnosis which requires management by general surgeons. Morbidity from cholecystitis is often life-threatening, especially in patients with underlying liver cirrhosis or other medical comorbidities. Diagnosis and management of this disease can vary among providers and hospitals. The decision to utilize a radiological or endoscopic temporizing maneuver in severe acute cholecystitis and the timing of later definitive cholecystectomy are relevant points of discussion within general surgery societies. In the last 5 years, the use of intraoperative ductal imaging by conventional vs fluorescence cholangiography had gained significant interest due to the widespread availability of indocyanine green. Finally, the operative strategies and how to manage intra-/postoperative complications are very important to optimizing patient outcomes. In this review paper, we discuss all treatment aspects of cholecystitis and provide updates in its management.

Predictors and benefits of multiagent chemotherapy for pancreatic adenocarcinoma: Timing matters.

INTRODUCTION: Adjuvant (A) multiagent chemotherapy (MC) is the standard of care for patients with pancreatic adenocarcinoma (PDAC). Tolerating MC following a morbid operation may be difficult, thus neoadjuvant (NA) treatment is preferable. This study examined how the timing of chemotherapy was related to the regimen given and ultimately the overall survival (OS). METHODS: The National Cancer Database was queried from 2006 to 2017 for nonmetastatic PDAC patients who underwent surgical resection and received MC or single-agent chemotherapy (SC) pre- or postresection. Predictors of receiving MC were determined using multivariable logistic regression. Five-year OS was evaluated using the Kaplan-Meier and Cox proportional hazards model. RESULTS: A total of 12,440 patients (NA SC, n = 663; NA MC, n = 2313; A SC, n = 6152; A MC, n = 3312) were included. MC utilization increased from 2006-2010 to 2011-2017 (33.1%-49.7%; odds ratio [OR]: 0.59; p < 0.001). Younger age, fewer comorbidities, higher clinical stage, and larger tumor size were all associated with receipt of MC (all p < 0.001), but NA treatment was the greatest predictor (OR 5.18; 95% confidence interval [CI]: 4.63-5.80; p < 0.001). MC was associated with increased median 5-year OS (26.0 vs. 23.9 months; hazard ratio [HR]: 0.92; 95% CI: 0.88-0.96) and NA MC was associated with the highest survival (28.2 months) compared to NA SC (23.3 months), A SC (24.0 months), and A MC (24.6 months; p < 0.001). CONCLUSION: Use and timing of MC contribute to OS in PDAC with an improved 5-year OS compared to SC. The greatest predictor of receiving MC was being given as NA therapy and the greatest survival benefit was the NA MC subgroup. Randomized studies evaluating the timing of effective MC in PDAC are needed.

Bacteriophage endolysin treatment for systemic infection of Streptococcus iniae in hybrid striped bass.

Streptococcus iniae, a zoonotic Gram-positive pathogen, poses a threat to finfish aquaculture, causing streptococcosis with an annual economic impact exceeding $150 million globally. As aquaculture trends shift towards recirculating systems, the potential for horizontal transmission of S. iniae among fish intensifies. Current vaccine development provides only short-term protection, driving the widespread use of antibiotics like florfenicol. However, this practice raises environmental concerns and potentially contributes to antibiotic resistance. Thus, alternative strategies are urgently needed. Endolysin therapy, derived from bacteriophages, employs hydrolytic endolysin enzymes that target bacterial peptidoglycan cell walls. This study assesses three synthetic endolysins (PlyGBS 90-1, PlyGBS 90-8, and ClyX-2) alongside the antibiotic carbenicillin in treating S. iniae-infected hybrid striped bass (HSB). Results demonstrate that ClyX-2 exhibits remarkable bacteriolytic potency, with lytic activity detected at concentrations as low as ∼15 µg/mL, approximately 8-fold more potent than the PlyGBS derivatives. In therapeutic effectiveness assessments, both carbenicillin and ClyX-2 treatments achieved significantly higher survival rates (85 % and 95 %, respectively) compared to placebo and PlyGBS-based endolysin treatments. Importantly, no statistical differences were observed between ClyX-2 and carbenicillin treatments. This highlights ClyX-2 as a promising alternative for combating S. iniae infections in aquaculture, offering potent bacteriolytic activity and high survival rates.

Hemorragia por hipertensión portal (HTP) secundaria a variz éctopica en ureteroileostomía tipo Bricker en un paciente con dos trombosis precoces consecutivas de la derivación portosistémica intrahepática transyugular (TIPS) / Portal hypertension hemorrhage secondary to a stomal varicose vein in a patient with two consecutive thrombosis of a transjugular intrahepatic portosystemic shunt (TIPS)

Less than 5% of patients with liver cirrhosis (LC) with portal hypertension (PH) develop atypical shunt (in regions other than the esophagus or the stomach). Within this group are varices associated with a stoma, for example the ones associated with an uretero-ileostomy which are infrequent. They are a diagnostic and therapeutic challenge, as they can cause hemorrhages due to PH. We present a clinical case about stoma varicose bleeding as the latest guidelines for the management of PH do not mention them or their treatment due to their low incidence.(AU)

SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies. METHODS: A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations. RESULTS: The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence). CONCLUSION: Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.

Immunogenic epitope scanning in bacteriolytic enzymes Pal and Cpl-1 and engineering Pal to escape antibody responses.

Bacteriolytic enzymes are promising antibacterial agents, but they can cause a typical immune response in vivo. In this study, we used a targeted modification method for two antibacterial endolysins, Pal and Cpl-1. We identified the key immunogenic amino acids, and designed and tested new, bacteriolytic variants with altered immunogenicity. One new variant of Pal (257-259 MKS → TFG) demonstrated decreased immunogenicity while a similar mutant (257-259 MKS → TFK) demonstrated increased immunogenicity. A third variant (280-282 DKP → GGA) demonstrated significantly increased antibacterial activity and it was not cross-neutralized by antibodies induced by the wild-type enzyme. We propose this variant as a new engineered endolysin with increased antibacterial activity that is capable of escaping cross-neutralization by antibodies induced by wild-type Pal. We show that efficient antibacterial enzymes that avoid cross-neutralization by IgG can be developed by epitope scanning, in silico design, and substitutions of identified key amino acids with a high rate of success. Importantly, this universal approach can be applied to many proteins beyond endolysins and has the potential for design of numerous biological drugs.

Thermal Characterization and Interaction of the Subunits from the Multimeric Bacteriophage Endolysin PlyC.

Bacteriophage endolysins degrade the bacterial peptidoglycan and are considered enzymatic alternatives to small-molecule antibiotics. In particular, the multimeric streptococcal endolysin PlyC has appealing antibacterial properties. However, a comprehensive thermal analysis of PlyC is lacking, which is necessary for evaluating its long-term stability and downstream therapeutic potential. Biochemical and kinetic-based methods were used in combination with differential scanning calorimetry to investigate the structural, kinetic, and thermodynamic stability of PlyC and its various subunits and domains. The PlyC holoenzyme structure is irreversibly compromised due to partial unfolding and aggregation at 46 °C. Unfolding of the catalytic subunit, PlyCA, instigates this event, resulting in the kinetic inactivation of the endolysin. In contrast to PlyCA, the PlyCB octamer (the cell wall-binding domain) is thermostable, denaturing at ~75 °C. The isolation of PlyCA or PlyCB alone altered their thermal properties. Contrary to the holoenzyme, PlyCA alone unfolds uncooperatively and is thermodynamically destabilized, whereas the PlyCB octamer reversibly dissociates into monomers and forms an intermediate state at 74 °C in phosphate-buffered saline with each subunit subsequently denaturing at 92 °C. Adding folded PlyCA to an intermediate state PlyCB, followed by cooling, allowed for in vitro reconstitution of the active holoenzyme.

A unique borrelial protein facilitates microbial immune evasion.

IMPORTANCE: Lyme disease is a major tick-borne infection caused by a bacterial pathogen called Borrelia burgdorferi, which is transmitted by ticks and affects hundreds of thousands of people every year. These bacterial pathogens are distinct from other genera of microbes because of their distinct features and ability to transmit a multi-system infection to a range of vertebrates, including humans. Progress in understanding the infection biology of Lyme disease, and thus advancements towards its prevention, are hindered by an incomplete understanding of the microbiology of B. burgdorferi, partly due to the occurrence of many unique borrelial proteins that are structurally unrelated to proteins of known functions yet are indispensable for pathogen survival. We herein report the use of diverse technologies to examine the structure and function of a unique B. burgdorferi protein, annotated as BB0238-an essential virulence determinant. We show that the protein is structurally organized into two distinct domains, is involved in multiplex protein-protein interactions, and facilitates tick-to-mouse pathogen transmission by aiding microbial evasion of early host cellular immunity. We believe that our findings will further enrich our understanding of the microbiology of B. burgdorferi, potentially impacting the future development of novel prevention strategies against a widespread tick-transmitted infection.

Covariation between oxygen and hydrogen stable isotopes declines along the path from xylem water to wood cellulose across an aridity gradient.

Oxygen and hydrogen isotopes of cellulose in plant biology are commonly used to infer environmental conditions, often from time series measurements of tree rings. However, the covariation (or the lack thereof) between δ18 O and δ2 H in plant cellulose is still poorly understood. We compared plant water, and leaf and branch cellulose from dominant tree species across an aridity gradient in Northern Australia, to examine how δ18 O and δ2 H relate to each other and to mean annual precipitation (MAP). We identified a decline in covariation from xylem to leaf water, and onwards from leaf to branch wood cellulose. Covariation in leaf water isotopic enrichment (Δ) was partially preserved in leaf cellulose but not branch wood cellulose. Furthermore, whilst δ2 H was well-correlated between leaf and branch, there was an offset in δ18 O between organs that increased with decreasing MAP. Our findings strongly suggest that postphotosynthetic isotope exchange with water is more apparent for oxygen isotopes, whereas variable kinetic and nonequilibrium isotope effects add complexity to interpreting metabolic-induced δ2 H patterns. Varying oxygen isotope exchange in wood and leaf cellulose must be accounted for when δ18 O is used to reconstruct climatic scenarios. Conversely, comparing δ2 H and δ18 O patterns may reveal environmentally induced shifts in metabolism.

Visual outcomes after bevacizumab-based therapy for optic pathway glioma.

In optic pathway glioma (OPG), bevacizumab-based therapy (BBT) has promising effects on radiographic tumor burden, but the impact on vision is less clear. This single-institution study characterized visual acuity (VA) and visual field (VF) outcomes in 17 pediatric OPG patients treated with BBT. VA was stable or improved in 14 patients. Nine patients had evaluable VF data, six of whom experienced stability or improvement. Among six patients with vision deterioration as a treatment indication, stable or improved was observed for both VA and VF in five patients. In summary, BBT was associated with favorable visual outcomes in this cohort of patients with OPG.

Smartphone AF Burden During the Blanking Period Predicts Catheter Ablation Outcomes: Insights From DECAAF II.

BACKGROUND: Atrial fibrillation (AF) recurrence during the blanking period is under investigated. With the rise of smartphone-based electrocardiogram (ECG) monitoring, there's potential for better prediction and understanding of AF recurrence trends. OBJECTIVES: In this study the authors hypothesize that AF burden derived from a single-lead Smartphone ECG during the blanking period predicts recurrence of atrial arrhythmias after ablation. METHODS: 630 patients with persistent AF undergoing ablation were included from the DECAAF II (Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) trial. Patients recorded daily ECG strips using a smartphone device. AF burden was defined as the ratio of ECG strips with AF to the total number of strips submitted. The primary outcome was the recurrence of atrial arrhythmia. RESULTS: Recurrence occurred in 301 patients during the 18-month follow-up period. In patients who developed recurrent arrhythmia after 90 days of follow-up, AF burden during the blanking period was significantly higher when compared with patients who remained in sinus rhythm (31.3% vs 7.5%; P < 0.001). AF burden during the blanking period was an independent predictor of arrhythmia recurrence (HR: 1.41; 95% CI: 1.36-1.47; P < 0.001). Through grid searching, an AF burden of 18% best discriminates between recurrence and no-recurrence groups, yielding a C-index of 0.748. After a follow-up period of 18 months, recurrence occurred in 33.7% of patients (147 of 436) with an AF burden <18% and in 79.4% of patients (154 of 194) with an AF burden >18% (HR: 4.57; 95% CI: 3.63-5.75; P < 0.001). CONCLUSIONS: A high AF burden derived from a smartphone ECG during the blanking period is a strong predictor of atrial arrhythmia recurrences after ablation.

Quality of life after pancreatoduodenectomy: Is the outcome predetermined by the diagnosis?

BACKGROUND AND OBJECTIVES: Non-physiological factors tied to the disease process may drive the diminished quality of life (QoL) after pancreatoduodenectomy (PD). We compared postoperative QoL among patients undergoing PD for either benign or malignant pathology. METHODS: From 2012 to 2021, 228 patients underwent PD in a large healthcare system. Eighty-two patients (36.0%) were interviewed using the EORTC QLQ-C30 questionnaire. A minimum of 6 months after surgery was required for the survey. QoL outcomes were compared based on diagnosis (benign vs. malignant). RESULTS: Patient mean age was 65 years (21-82), and forty-seven (57%) were men. Most patients underwent surgery for cancer, 76% (n = 62). Grade B postoperative pancreatic fistula incidence was higher in benign cases (30% vs. 6.5%, p = 0.024). Weight loss was more common in malignancy (79% vs. 50%, p = 0.016). Carcinoma patients felt less useful, hopeful, reported less control of their life and certainty of the future, and were less satisfied with their appearance. Carcinoma patients also reported diminished memory, fear of relapse, and greater financial burden. CONCLUSIONS: Long-term QoL is inferior in PD patients with carcinoma and is driven by the psychological and socioeconomic implications of malignancy. Supportive resources for pancreas cancer patients should be evaluated and optimized.

Portal hypertension hemorrhage secondary to a stomal varicose vein in a patient with two consecutive thrombosis of a transjugular intrahepatic portosystemic shunt (TIPS).

Less than 5% of patients with liver cirrhosis (LC) with portal hypertension (PH) develop atypical shunt (in regions other than the esophagus or the stomach). Within this group are varices associated with a stoma, for example the ones associated with an uretero-ileostomy which are infrequent. They are a diagnostic and therapeutic challenge, as they can cause hemorrhages due to PH. We present a clinical case about stoma varicose bleeding as the latest guidelines for the management of PH do not mention them or their treatment due to their low incidence.

Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Nonmetastatic Pancreatic Adenocarcinoma.

BACKGROUND: Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival. PATIENTS AND METHODS: From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma. SAS was defined as pancreatic resection with negative margins and ≥ 15 lymph nodes examined. Stage-specific GRT was defined by current National Comprehensive Cancer Network guidelines. Multivariable models were used to determine predictors of adherence to SAS and GRT and prognostic impact on overall survival. RESULTS: Overall, SAS was achieved in 39% and GRT in 65% of patients, but only 30% received both SAS and GRT. Increasing age, minority race, uninsured status, and greater comorbidities were associated with a decreased odds of receiving both SAS and GRT (all p < 0.05). SAS (HR 0.79; CI 0.76-0.81; p < 0.001) and GRT (HR 0.67; CI 0.65-0.69; p < 0.001) were each independently associated with a survival advantage. Receipt of both SAS and GRT was associated with significant improvement in median OS compared with receiving neither (2.2 years vs 1.1 years; p < 0.001) which was independently associated with a 78% increased risk of death (HR 1.78; CI 1.70-1.86; p < 0.001). CONCLUSIONS: Despite survival benefits associated with adherence to operative standards and receipt of guideline-recommended therapy, compliance remains poor. Future efforts must be directed toward improved education and implementation efforts around both operative standards and therapy guidelines.

Identifying the prognostic significance of early arrhythmia recurrence during the blanking period and the optimal blanking period duration: insights from the DECAAF II study.

OBJECTIVE: Early atrial arrhythmia recurrence following atrial fibrillation (AF) ablation is common. Current guidelines promulgate a 3-month blanking period. We hypothesize that early atrial arrhythmia recurrence during the blanking period may predict longer-term ablation outcomes. METHODS AND RESULTS: A total of 688 patients with persistent AF undergoing catheter ablation were included in the DECAAF II trial database. The primary endpoint of the study was the first confirmed recurrence of atrial arrhythmia. Recurrence was also monitored during the 90-day blanking period. A total of 287 patients experienced recurrent atrial arrhythmia during the blanking period, while 401 remained in sinus rhythm. Rates of longer-term arrhythmia recurrence were substantially higher among those who developed recurrence during the blanking period compared to those who remained in sinus rhythm throughout the blanking period (68% vs. 32%, P < 0.001). The study cohort was divided into three groups according to the timing of arrhythmia recurrence during the blanking period. Of those who had recurrent arrhythmia during the first month of the blanking period (Group 1), 43.9% experienced longer-term recurrence, compared to 61.6% who recurred during the second month of the blanking period (Group 2), and 93.3% of those who had arrhythmia recurrence during the third month (Group 3, P < 0.001). The risk of recurrent arrhythmia was highest in Group 3 (HR = 10.15), followed by Group 2 (HR = 2.35) and Group 1 (HR = 1.5). Receiver operating characteristic analysis was performed to assess the relationship between the timing of arrhythmia recurrence and the primary outcome (AUC = 0.746, P < 0.001). The optimal blanking period duration was identified as 34 days. Atrial fibrillation burden determined by smartphone electrocardiogram technology over the 18 months follow-up period was significantly higher in Group 3 (29%) compared to Groups 1 (6%) and 2 (7%) and in patients who stayed in sinus rhythm during the blanking period (5%) (P < 0.0001). CONCLUSION: Early atrial arrhythmia recurrence during the blanking period, particularly during the third month, is significantly associated with later recurrence. Although a blanking period is warranted, it should be abbreviated.

Understanding the Molecular Basis for Homodimer Formation of the Pneumococcal Endolysin Cpl-1.

The rise of multi-drug-resistant bacteria that cannot be treated with traditional antibiotics has prompted the search for alternatives to combat bacterial infections. Endolysins, which are bacteriophage-derived peptidoglycan hydrolases, are attractive tools in this fight. Several studies have already demonstrated the efficacy of endolysins in targeting bacterial infections. Endolysins encoded by bacteriophages that infect Gram-positive bacteria typically possess an N-terminal catalytic domain and a C-terminal cell-wall binding domain (CWBD). In this study, we have uncovered the molecular mechanisms that underlie formation of a homodimer of Cpl-1, an endolysin that targets Streptococcus pneumoniae. Here, we use site-directed mutagenesis, analytical size exclusion chromatography, and analytical ultracentrifugation to disprove a previous suggestion that three residues at the N-terminus of the CWBD are involved in the formation of a Cpl-1 dimer in the presence of choline in solution. We conclusively show that the C-terminal tail region of Cpl-1 is involved in formation of the dimer. Alanine scanning mutagenesis generated various tail mutant constructs that allowed identification of key residues that mediate Cpl-1 dimer formation. Finally, our results allowed identification of a consensus sequence (FxxEPDGLIT) required for choline-dependent dimer formation─a sequence that occurs frequently in pneumococcal autolysins and endolysins. These findings shed light on the mechanisms of Cpl-1 and related enzymes and can be used to inform future engineering efforts for their therapeutic development against S. pneumoniae.

Can Breaking Heroin Addiction Lead to a Broken Heart? A Case of Reverse Takotsubo Cardiomyopathy in a Patient With Heroin Withdrawal.

Reverse takotsubo cardiomyopathy is triggered by emotional or physical stress and has a presentation similar to that of acute coronary syndrome. A 39-year-old woman with a history of heroin use disorder presented with intractable nausea, vomiting, and diarrhea. She was diagnosed with heroin withdrawal and started on buprenorphine-naloxone. On day 2 of her hospitalization, she developed chest heaviness and had an elevated troponin I level of 3.2 ng/mL (reference range, 0.015-0.045 ng/mL); electrocardiography showed new T-wave inversions in the anterior and inferior leads. Emergent coronary angiography showed patent coronary arteries, and left ventriculography showed basal hypokinesis and apical hyperkinesis, consistent with reverse takotsubo cardiomyopathy secondary to heroin withdrawal. She was started on antihypertensive agents, and her buprenorphine-naloxone dose was increased. At her 3-month follow-up visit, she reported no symptoms consistent with angina or heart failure. This appears to be the first report of heroin withdrawal causing reverse takotsubo cardiomyopathy. Awareness of this association can lead to earlier recognition and treatment of reverse takotsubo cardiomyopathy.