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Improving the energy efficiency of room air conditioners (RACs) while transitioning to low global-warming-potential (GWP) refrigerants will be a critical step toward reducing the energy, peak load, and emissions impacts of RACs while keeping costs low. Previous research quantified the benefits of leapfrogging to high efficiency in tandem with the transition to low-GWP refrigerants for RACs (Shah et al., 2015) and identified opportunities for initial action to coordinate energy efficiency with refrigerant transition in economies constituting about 65% of the global RAC market (Shah et al., 2017).This report describes further research performed to identify the best-performing (i.e., most efficient and low-GWP-refrigerant using) RACs on the market, to support an understanding of the best available technology (BAT). Understanding BAT can help support market-transformation programs for high-efficiency and low-GWP equipment such as minimum energy performance standards (MEPS), labeling, procurement, and incentive programs.We studied RACs available in six economies—China, Europe, India, Japan, South Korea, and the United States—that together account for about 70% of global RAC demand, as well as other emerging economies. The following are our key findings:•Highly efficient RACs using low-GWP refrigerants, e.g., HFC-32 (R-32) and HC-290 (R-290), are commercially available today at prices comparable to similar RACs using high-GWP HCFC-22 (R-22) or HFC-410A (R-410A).•High efficiency is typically a feature of high-end products. However, highly efficient, cost-competitive (less than 1,000 or 1,500 U.S. dollars in retail price, depending on size) RACs are available.•Where R-22 is being phased out, high GWP R-410A still dominates RAC sales in most mature markets except Japan, where R-32 dominates. •In all of the economies studied except Japan, only a few models are energy efficient and use low-GWP refrigerants. For example, in Europe, India, and Indonesia, the highest-efficiency RAC models employ the low-GWP refrigerants R-32 or R-290.•RACs are available in most regions and worldwide that surpass the highest efficiency levels recognized by labeling programs.•Fixed-speed RACs using high-GWP and ozone-depleting R-22 refrigerant still dominate the market in many emerging economies. There is significant scope to improve RAC efficiency and transition to low-GWP refrigerants using commercially available technology and to design market-transformation programs for high-efficiency, low-GWP equipment including standards, labeling, procurement, and incentive programs.

In October of 2016, nearly 200 Parties agreed to amend the Montreal Protocol in Kigali, Rwanda, to phase-down consumption and production of hydrofluorocarbons (HFCs) by 2050. Growth in the use of HFCs, including those currently used as refrigerants in air-conditioning systems, is being driven by demand from emerging economies, hot climates, and rising incomes that are also undergoing rapid urbanization and electrification. Air conditioners (ACs), as an energy-intensive end-use technology, are also covered by a growing number of energy efficiency standards, labeling, procurement, incentive, and other supporting efficiency programs. Therefore, improving room AC energy efficiency and transitioning to low-global warming potential (GWP) refrigerants simultaneously presents significant opportunities to deploy energy efficient technology and reduce the energy and emissions impacts of room ACs, while keeping costs low for consumers.This report aims to provide an initial sense of the opportunities to improve efficiency and transition to low-GWP refrigerants by reviewing the HCFC and HFC regulatory framework and energy efficiency standards and labeling programs in 19 economies that account for roughly 65 percent of global room AC demand. Based on this analysis, we identified key opportunities for coordinated action on efficiency improvement and refrigerant transition for the domestic room AC sector (i.e., ductless mini-split ACs), such as:- implementing or revising standards and labeling programs to improve efficiency levels with the possibility of adding a low-GWP criterion.- combining fixed speed and inverter AC product categories to account for seasonal variations in climate and part-load operating conditions, and using seasonal energy efficiency ratio (SEER) instead of energy efficiency ratio (EER) to better reflect performance of inverter ACs.- implementing market transformation programs, such as bulk procurement programs, to drive down the costs of efficient technology through economies of scale.- aligning timelines for implementing efficiency standards with timelines for refrigerant management plans to coordinate policy actions.- maximizing the energy efficiency improvements of Montreal Protocol investments by coordinating efforts to help keep costs low for consumers and manufacturers during equipment redesign and manufacturing line retooling for refrigerant transition.In order to realize the significant peak load, energy saving and climate benefits of these opportunities associated with improving energy efficiency in tandem with the refrigerant transition, some risks may need to be mitigated, principally safety concerns over risks of accidental ignition with refrigerants rated flammable. This can be mitigated by continuing and accelerating the development of safety standards currently being updated, for example, by the International Electrotechnical Commission (IEC) and improving training for production, installation and maintenance during the use of flammable refrigerants. While some low-GWP refrigerants may cost more than the current baseline refrigerants, the cost of refrigerants is only ~1% of lifecycle costs for an AC. Costs can also be reduced through manufacturing advances and efficiency improvements, particularly if they are supported by policies that encourage technological development through deployment of superefficient ACs at scale. Finally, during the transition, there is a risk of obsolete technology being deployed in markets that either have not updated their standards or have later compliance dates. This risk can be mitigated by updating standards and reviewing them periodically to ensure their effectiveness.

Blood pressure (BP) characteristics, such as central aortic pressure and arterial stiffness, independently predict cardiovascular events. The effects of pharmacologically dissimilar β-blockers on these properties have not been fully elucidated. Patients with essential hypertension and without significant concomitant cardiovascular disease were randomly assigned to controlled-release carvedilol, force-titrated to 80 mg (n=22), or atenolol, force-titrated to 100 mg (n=19); each was given once daily for 4 weeks. Baseline characteristics were similar. At the end of week 4, atenolol and carvedilol reduced central and brachial systolic and diastolic BP to a similar extent. Central augmentation index was increased in atenolol-treated patients but not carvedilol-treated patients (atenolol 4.47% vs carvedilol -0.68%; P=.04). Mean augmented central aortic pressure increased slightly during atenolol treatment (+1.1 mm Hg) but decreased slightly during carvedilol treatment (-1.1 mm Hg), although the difference in these changes was not statistically significant (P=.23). Pulse pressure amplification was reduced more with atenolol at week 4 (atenolol -10.7% vs carvedilol -1.8%; P=.02). Therefore, we conclude that carvedilol results in more favorable pulse pressure amplification and augmentation index by increasing arterial compliance and reducing the magnitude of wave reflection, respectively, compared with atenolol. [ABSTRACT FROM AUTHOR]

The purpose of this study was to better characterize morphine equivalent daily dose (MEDD) equivalencies with buccal buprenorphine, and identify real-world efficacy and safety outcomes associated with the use of buccal buprenorphine for chronic pain at a local VA Medical Center. This study was a retrospective chart review of Computerized Patient Record System (CPRS) patient records with outpatient prescriptions for buccal buprenorphine (Belbuca ® ). Overall, there was a high discontinuation rate of Belbuca ® : being 60% or greater across all different patient groups. These high attrition rates may potentially be result of failure to titrate to an optimal dose of Belbuca ® needed for adequate analgesia. Those fully rotated fared marginally better than those partially rotated in that those fully rotated discontinued at a lesser rate and less quickly than those who were partially rotated. From the results of this study, a local dosing scheme for Belbuca ® based on baseline MEDD was created for facility level guidance. The exact MEDD conversion ratio, however, for individual buprenorphine products as well as MEDD contributed by these products on a patient's overall opioid related risk compared to other full agonist opioids still remains unclear and further studies are warranted.

Background: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity., Methods: In this two-part retrospective, observational study, we first compared mutational landscapes in haematopoietic stem and progenitor cells (HSPCs) from patients with advanced-stage Hodgkin lymphoma in remission for at least 6 months who had been treated with eBEACOPDac (eBEACOPDac cohort), eBEACOPP (real-world eBEACOPP cohort), or doxorubicin-bleomycin-vinblastine-dacarbazine (ABVD); in buccal DNA from five children of a female patient with classical Hodgkin lymphoma treated with eBEACOPP before conceiving the third child; in sperm DNA from a patient with mild oligospermia treated with eBEACOPP; and in caecal adenocarcinoma and healthy colon tissue from a survivor of Hodgkin lymphoma treated with chlorambucil-vinblastine-procarbazine-prednisolone. For the second part, we analysed efficacy and toxicity data from adult patients (aged >16 years) treated with first-line eBEACOPDac (eBEACOPDac cohort) at 25 centres across UK, Ireland, and France; efficacy was compared with the German HD18 eBEACOPP trial data and toxicity with a UK real-world dataset. Participants in the German HD18 and UK real-world datasets were adults (aged >16 years) with previously untreated Hodgkin lymphoma, treated with first-line eBEACOPP. We had two co-primary objectives: to define the comparative stem-cell mutation burden and mutational signatures after treatment with or without procarbazine-containing chemotherapy (first study part); and to determine progression-free survival of patients with Hodgkin lymphoma treated with eBEACOPP or eBEACOPDac (second study part). Secondary objectives included overall survival and explored differences in specific toxicity outcomes, including transfusion requirements and measures of reproductive health (second study part)., Findings: In the first part of the study (mutational analysis), patients treated with eBEACOPP (n=5) exhibited a higher burden of point mutations in HSPCs compared with those treated with eBEACOPDac (n=4) or ABVD (n=3; excess mutations 1150 [95% CI 934-1366] vs 290 [241-339] vs 186 [116-254]). Two novel mutational signatures, SBSA (SBS25-like) and SBSB, were identified in HSPCs and in a single neoplastic and healthy colon sample from patients who received procarbazine-containing chemotherapy. SBSB was also identified in germline DNA of three children conceived after eBEACOPP and in sperm of a male patient treated with eBEACOPP. SBSC was detected in patients treated with either ABVD or eBEACOPDac. In the second part of the study (efficacy and toxicity analysis), dacarbazine substitution did not appear to compromise efficacy or safety. 312 patients treated with eBEACOPDac (eBEACOPDac cohort; treated 2017-22, 186 [60%] male, median follow-up 36·0 months [IQR 25·2-50·1]) had a 3-year progression-free survival of 93·3% (95% CI 90·3-96·4), which was similar to the 93·3% [95% CI 92·1-94·4]) progression-free survival seen in 1945 patients in the German HD18 eBEACOPP trial (treated 2008-14, 1183 [61%] male, median follow-up 57·0 months [35·4-64·7]). Patients treated with eBEACOPDac required fewer blood transfusions (mean 1·70 units [SD 2·77] vs 3·69 units [3·89]; p<0·0001), demonstrated higher post-chemotherapy sperm concentrations (median 23·4 million per mL [IQR 11·0-632·3] vs 0·0 million per mL [0·0-0·001]; p=0·0040), and had earlier resumption of menstrual periods (mean 5·04 months [SD 3·07] vs 8·77 months [5·57]; p=0·0036) compared with 73 patients treated with eBEACOPP in the UK real-world dataset., Interpretation: Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy., Funding: Addenbrooke's Charitable Trust and Wellcome Trust., Competing Interests: Declaration of interests AS reports support for meetings or conferences from Takeda. WO reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Takeda, Pfizer, Servier, Kite Gilead, MSD, Novartis, Beigene, AstraZeneca, Syneos, Autolus, Kywoa Kirin, AbbVie, Incyte, BMS, Janssen, and Sobi. GCP reports honoraria for speaker and advisory work from Takeda, Roche, Kite, AbbVie, Beigene, AstraZeneca, Sobi, and Secura Bio; and support for research from Beigene, Pfizer, BMS, Amgen, and AstraZeneca. DD reports speaker fees from AbbVie and support for travel to conferences from AstraZeneca and Beigene. PM reports support for meetings or conferences from Takeda. EHP reports honoraria for advisory work and support for meetings or conferences from Takeda. EL reports research support from CSL Behring. PB reports consulting fees from Takeda, BMS, Roche, Amgen, Novartis, Celgene, Miltenyi Biotech, and Gilead; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda, Novartis, BMS, Roche, MSD, Celgene, Miltenyi Biotech, Gilead, and AbbVie; and funding for scientific research from Takeda Oncology, MSD, and Novartis. SB reports consulting fees from Galapagos; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and consultation from Takeda; financial support for attending meetings or travel from Takeda; having a leadership role in another board, society, committee, or advocacy group (paid or unpaid), and holding stock or stock options for Liqomics. GAF reports honoraria for advisory work and support for meetings or conferences from Takeda. EM, MHP, RS, JJ, HLS, KS, PB, TFM, TC, KMA, JB, SB, KB, SB, NDC, DJC, KC, AD, AD, MF, EGE, AH, DH, HH, SI, SGJ, MK, KML, OCL, NMC, AM, SKN, NP, JFR, NKS, GS, AS, RT, BJU, NW, XYZ, AKM, NC, MRS, PJC, and RR declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Fournier's gangrene, a polymicrobial infection affecting the scrotum and perineal area, predominantly affects elderly males, presenting challenges in diagnosis and management. This report examines two cases, with a focus on the rare outcome of bilateral orchidectomy., Case Presentation: A 69-year-old diabetic male presented with severe penile and scrotal pain, leading to the diagnosis of Fournier's gangrene. In another case, a 91-year-old male with a history of Benign Enlargement of the Prostate experienced scrotal pain and ulcerative lesions, resulting in a rapid progression of gangrene. The surgical approaches encompassed multiple debridement and bilateral orchidectomy, underscoring the intricate nature of managing Fournier's gangrene., Discussion: Fournier's gangrene typically originates as a polymicrobial infection in the genitourinary or perianal regions, with common risk factors including diabetes, immunosuppression, and advanced age. Diagnosis often relies on clinical assessment, though imaging aids in complex cases. Early intervention with broad-spectrum antibiotics and repeated debridement remains the cornerstone of treatment., Conclusion: Fournier's gangrene, a rare condition, poses diverse clinical presentations, management strategies, and outcomes. Early recognition, aggressive surgical debridement, and a multidisciplinary approach are essential in managing this condition., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Salmonella enterica serovar Hvittingfoss, a member of the non-typhoidal Salmonella group, is an important foodborne serovar most frequently identified in regions (Australia, Belgium, and the United States) with active surveillance systems. This serovar has been implicated in outbreaks of foodborne illness. Soft cheese, crab cocktail, beef, and rock melon are commonly involved in these outbreaks. Although the definitive host of this serovar is not yet established, Salmonella Hvittingfoss can be found in wild animals (Feral pigs), bird populations (Bar-tailed godwit, Plumed whistling ducks, White-naped crane, and Sharp-tailed sandpiper), and domestic birds like chickens. Case presentation: We report the first case of Salmonella enterica serovar Hvittingfoss causing acute gastroenteritis in a 52-year-old male labourer and agriculturist from a rural area of Mysuru, South India. This is the first documented case of Salmonella Hvittingfoss causing acute gastroenteritis in India. Conclusions: While non-typhoidal Salmonella infections typically resolve on their own, they can be particularly dangerous for certain demographics, such as children, the elderly, and those with compromised immune systems. Therefore, studying the different serotypes of these infections in both clinical and subclinical cases is crucial for targeting effective surveillance, hygiene practises, and food safety measures that can mitigate their impact on public health.

Buprenorphine has demonstrated benefit for acute and chronic pain and various psychiatric disorders. However, many studies evaluating buprenorphine's effect on psychiatric conditions are not specific to the chronic pain population. This retrospective study was conducted to assess the impact of buprenorphine on depressive symptoms in patients with chronic pain at a Veterans Affairs healthcare facility. Adults with chronic pain started on any formulation of buprenorphine or traditional opioid (non-buprenorphine opioid) with at least two depression screenings between May 1, 2016 and November 1, 2021 were included. The primary outcome was change in depressive symptoms, measured by Patient Health Questionnaire-9 (PHQ-9), from baseline to 6-18 months after starting therapy. Secondary outcomes included changes in Columbia-Suicide Severity Rating Scale and mental health services utilization. Twenty-one patients were included. Median baseline PHQ-9 in the buprenorphine and traditional opioid groups were 14 and 13, respectively. Median change in PHQ-9 was -5 in the buprenorphine group and -1.5 in the traditional opioid group. Compared to traditional opioids, buprenorphine was associated with a greater reduction in depressive symptoms among Veterans with chronic pain. Although this reduction met the threshold for clinically significant improvement, further investigation is needed to evaluate the clinical relevance of these findings.

This case report details the clinical management and implications of infection with pan-drug-resistant Providencia rettgeri in a 50-year-old male admitted and diagnosed with acute peritonitis due to hollow viscus perforation, highlighting an emerging challenge in healthcare settings. Following emergency laparotomy and intensive care admission, the patient was catheterized to assist urine drainage and subsequent urine bacterial culture which yielded pan-drug-resistant P. rettgeri , signifying a notable instance of nosocomial infection by a multi-drug-resistant organism. Despite the organism's resistance to broad-spectrum antibiotics, clinical improvement was observed with levofloxacin treatment, underlining the potential discrepancy between in vitro resistance patterns and in vivo response, particularly in urinary tract infections (UTIs) where urine drug concentrations are pivotal. This case underscores the necessity for heightened surveillance, stringent infection control measures, and judicious antibiotic use in managing infections caused by pan-drug-resistant pathogens like P. rettgeri , challenging the traditional paradigms of antimicrobial resistance and therapy in hospital settings., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Neelambike Sumana et al.)

Background: Caring is a universally accepted concept attributed to the nursing profession despite its many nebulous and elusive interpretations. Nursing is seen primarily as a feminine occupation, people get surprised when they see and hear about a male nurse. It is one of the few professions where women outnumber men greatly as it deals with care and nurture. This study aims to assess the female nurse attitude at male nurses in Nepal., Methods: A cross-sectional study was conducted in Biratnagar, Morang from the month of March to May 2023. Ethical clearance was obtained from IRC of Nobel Medical College Teaching Hospital, Biratnagar. Web-based computerized data were collected among 200 female nurses using whats app and Messenger. Data were collected using the Likert scale (AMnQ), which is a standardized 5-point Likert scale that assesses female nurses’ attitudes toward male nurses. SPSS V 23 was used to analyze the data using descriptive and inferential statistical techniques., Results: In this study, more than half (55.0%) of the nurses have low-level attitudes toward male nurses. Furthermore, nearly half (48.5%) disagree nursing is suitable only for females, More than one-third (36.5%) disagree nursing is considered a low-level occupation for males, half of them (50%) strongly disagree male and female nurses both are equally required in the nursing profession and (35%) agrees people do not prefer to send males for the nursing profession., Conclusions: Thus the study concludes that majority of the female nurses have low attitude towards male nurses. Therefore, it can be considered as an initiation for having a conversation regarding making gender equality in nursing and creating awareness about the roles and their importance in this profession. Keywords Attitude; female nurse; male nurse.

Salmonella enterica serovar Newport is a human pathogen underreported in most developing countries. It is known for causing gastroenteritis and extraintestinal infections. In this case report, we report the case of ceftriaxone-resistant Salmonella enterica serovar Newport from South India, causing acute gastroenteritis in a sixty-year-old female patient having a history of antimicrobial therapy and recent hospital admission. Serovar Newport, especially among antibiotic-exposed patients, poses a significant public health threat due to its ability to acquire multidrug resistance. This emphasizes the necessity for robust surveillance and monitoring of nontyphoidal Salmonella infections, particularly given the limited data on serovar Newport in India. Vigilance in clinical practice and public health initiatives is crucial to effectively address the emergence and spread of multidrug-resistant strains., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sumana, Maheshwarappa, Rao, Deepashree, Karthik and Shah.)

Background: SARS-CoV-2 infection in pregnant women during the third trimester resulted in overall adverse pregnancy outcomes compared to non-infected controls and a unique humoral and cellular response at delivery. In this study we aimed to assess the impact of SARS-CoV-2 infection on maternal/neonatal peripartum outcomes andimmunological profiles., Method: In this study, we recruited 304 SARS-CoV-2 infected pregnant women and 910 SARS-CoV-2 non-infected pregnant women who were admitted for delivery. Peripartum and neonates' outcomes response to SARS-CoV-2 infection were analyzed. Furthermore, we characterized the antibody and cytokines profile in SARS-CoV-2 infected maternal blood (MB) and cord blood (CB). We also assessed routine laboratory tests and liver function tests in MB before labor. Unpaired T test, Mann-Whitney test and Spearman test were used to analyze the data., Results: SARS-CoV-2 infected pregnant women were significantly associated with increased risk of adverse pregnancy outcomes, including preterm labor (13.8% vs. 9.5%, p = 0.033) and meconium-stained amniotic fluid (8.9% vs. 5.5%, p = 0.039). The risk of low birth weight (< 2500 g) (10.5% vs. 6.5%, p = 0.021) and Apgar score < 8 at 1-minute (9.2% vs. 5.8%, p = 0.049) significantly increased in newborns from COVID-19 positive mothers than their counterparts. Our results showed that antibodies were increased in adverse-outcome SARS-CoV-2 infected mothers and their neonates, and abnormal proportion of immune cells were detected in SARS-CoV-2 infected mothers. While the immune response showed no difference between adverse-outcome infected pregnant women and normal-outcome infected pregnant women. Thus, SARS-CoV-2 infection during the third trimester of pregnancy induced a unique humoral and cellular response at delivery., Conclusion: SARS-CoV-2 infection closer to delivery could incline to adverse pregnancy outcomes. Therefore, the utmost care is required for SARS-CoV-2 infected pregnant women and their newborns., Trial Registration: The study protocol was approved by the Institutional Review Board of the First Hospital of Jilin University with the approval code number 23K170-001, and informed consent was obtained from all enrolled patients prior to sample collection., (© 2024. The Author(s).)

Tecovirimat is the first-line antiviral treatment recommended for severe mpox or for persons with mpox who are at risk for severe disease; tecovirimat is available in the United States under an expanded access investigational new drug (IND) protocol. During the 2022-2023 mpox outbreak, local U.S. health jurisdictions facilitated access to tecovirimat. In June 2022, Los Angeles County (LAC) rapidly developed strategies for tecovirimat distribution using existing medical countermeasure distribution networks established by the Public Health Emergency Preparedness Program and the Hospital Preparedness Program, creating a hub and spoke distribution network consisting of 44 hub facilities serving 456 satellite sites across LAC. IND patient intake forms were analyzed to describe mpox patients treated with tecovirimat. Tecovirimat treatment data were matched with case surveillance data to calculate time from specimen collection to patients receiving tecovirimat. Among 2,281 patients with mpox in LAC, 735 (32%) received tecovirimat during June 2022-January 2023. Among treated patients, approximately two thirds (508; 69%) received treatment through community clinics and pharmacies. The median interval from specimen collection to treatment was 2 days (IQR = 0-5 days). Local data collection and analysis helped to minimize gaps in treatment access and facilitated network performance monitoring. During public health emergencies, medical countermeasures can be rapidly deployed across a large jurisdiction using existing distribution networks, including clinics and pharmacies., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Purpose: Capecitabine is an oral chemotherapy used to treat many gastrointestinal cancers. Its complex dosing and narrow therapeutic index make medication adherence and toxicity management crucial for quality care., Methods: We conducted a pilot study of PENNY-GI, a mobile phone text messaging-based chatbot that leverages algorithmic surveys and natural language processing to promote medication adherence and toxicity management among patients with gastrointestinal cancers on capecitabine. Eligibility initially included all capecitabine-containing regimens but was subsequently restricted to capecitabine monotherapy because of challenges in integrating PENNY-GI with radiation and intravenous chemotherapy schedules. We used design thinking principles and real-time data on safety, accuracy, and usefulness to make iterative refinements to PENNY-GI with the goal of minimizing the proportion of text messaging exchanges with incorrect medication or symptom management recommendations. All patients were invited to participate in structured exit interviews to provide feedback on PENNY-GI., Results: We enrolled 40 patients (median age 64.5 years, 52.5% male, 62.5% White, 55.0% with colorectal cancer, 50.0% on capecitabine monotherapy). We identified 284 of 3,895 (7.3%) medication-related and 13 of 527 (2.5%) symptom-related text messaging exchanges with incorrect recommendations. In exit interviews with 24 patients, participants reported finding the medication reminders reliable and user-friendly, but the symptom management tool was too simplistic to be helpful., Conclusion: Although PENNY-GI provided accurate recommendations in >90% of text messaging exchanges, we identified multiple limitations with respect to the intervention's generalizability, usefulness, and scalability. Lessons from this pilot study should inform future efforts to develop and implement digital health interventions in oncology.

Introduction: Pathological unstable dislocation of the glenohumeral joint following septic arthritis is a rare condition. We report a case of 40 years old patient with pathological shoulder dislocation secondary to septic arthritis., Case Presentation: A 40 years old male patient presented to the Department of Orthopedics with chief complain of swelling and pain of Right upper extremity for 6 days. He had history of IV canula insertion to give fluids. Then he developed swelling of hand which progressively increased up to right shoulder. He also complained of severe pain over that region. X-ray showed anteromedial dislocation of humeral head. Aspiration of joint was done and the aspirate was sent for culture and sensitivity, which revealed Staphylococcus aureus. Incision and drainage was performed, about 500 ml of straw-colored pus mixed with synovial fluid extending up to sternum, posteriorly up to clavicle and laterally up to deltoid was estimated. Then we planned for open reduction and percutaneous pinning with K-wire. The intervention led to substantial loss of disability and regain of limited range of motion., Discussion: Septic Arthritis in adults is uncommon and complete dislocation of the glenohumeral joint associated with it is rare. Septicemia was a common complication among all treatment groups, with cultures most frequently indicating Staphylococcus aureus as the causative organism. Septic arthritis is most commonly caused by hematogenous but recently, the incidence of hematogenous septic arthritis has decreased, while local injection-induced septic arthritis has been increased specially in shoulder., Conclusion: Septic arthritis of the glenohumeral joint is rare condition in comparison with knee and hip joints. Therefore, the diagnosis requires a high index of suspicion, early evaluation and treatment of the affected shoulder. Our case is a good example of how we can use simple surgery techniques like open reduction and percutaneous fixation with K-wire in low and middle income countries where patient is not economically sound to afford arthroplasty., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Substance use increasingly contributes to early morbidity and mortality, which necessitates greater preparation of the healthcare workforce to mitigate its harm. The purpose of this systematic scoping review is to: 1) review published curricula on harm reduction for substance use implemented by undergraduate (UME) and graduate medical education (GME) in the United States and Canada, 2) develop a framework to describe a comprehensive approach to harm reduction medical education, and 3) propose additional content topics for future consideration., Methods: PubMed, Scopus, ERIC: Education Resources Information Center (Ovid), and MedEdPORTAL were searched. Studies included any English language curricula about harm reduction within UME or GME in the United States or Canada from 1993 until Nov 22, 2021. Two authors independently reviewed and screened records for data extraction. Data were analyzed on trainee population, curricula objectives, format, content, and evaluation., Results: Twenty-three articles describing 19 distinct educational programs across the United States were included in the final sample, most of which created their own curricula (n = 17). Data on educational content were categorized by content and approach. Most programs (85%) focused on introductory substance use knowledge and skills without an understanding of harm reduction principles. Based on our synthesis of the educational content in these curricula, we iteratively developed a Harm Reduction Educational Spectrum (HRES) framework to describe curricula and identified 17 discrete content topics grouped into 6 themes based on their reliance on harm reduction principles., Conclusions: Harm reduction is under-represented in published medical curricula. Because the drug supply market changes rapidly, the content of medical curricula may be quickly outmoded thus curricula that include foundational knowledge of harm reduction principles may be more enduring. Students should be grounded in harm reduction principles to develop the advanced skills necessary to reduce the physical harm associated with drugs while still simultaneously recognizing the possibility of patients' ongoing substance use. We present the Harm Reduction Educational Spectrum as a new framework to guide future healthcare workforce development and to ultimately provide the highest-quality care for patients who use drugs., (© 2023. The Author(s).)

The objective of this study was to understand the effect buprenorphine rotations have on respiratory risk and other safety outcomes. This was a retrospective observational study evaluating Veterans who underwent an opioid rotation from full-agonist opioids to buprenorphine products or to alternative opioids. The primary endpoint was change in the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD) score from baseline to six months post-rotation. Median baseline RIOSORD scores were 26.0 and 18.0 in the Buprenorphine Group and the Alternative Opioid Group, respectively. There was no statistically significant difference between groups in baseline RIOSORD score. At six months post-rotation, median RIOSORD scores were 23.5 and 23.0 in the Buprenorphine Group and Alternative Opioid Group, respectively. The difference in change in RIOSORD scores between groups was not statistically significant ( p  = 0.23). However, based on changes in RIOSORD risk class, an 11% and 0% decrease in respiratory risk was observed in the Buprenorphine and Alternative Opioid groups, respectively. This finding may be considered clinically significant given a change in risk was observed as predicted by RIOSORD score. Further research is needed to clarify the effect that opioid rotations have on respiratory depression risk and other safety outcomes.

Maternal-fetal immune tolerance is a process that involves complex interactions of the immune system, and myeloid-derived suppressor cells have emerged as one of the novel immunomodulator in the maintenance of maternal-fetal immune tolerance. Myeloid-derived suppressor cells are myeloid progenitor cells with immunosuppressive activities on both innate and adaptive cells through various mechanisms. Emerging evidence demonstrates the accumulation of myeloid-derived suppressor cells during healthy pregnancy to establish maternal-fetal immune tolerance, placentation, and fetal-growth process. By contrast, the absence or decreased myeloid-derived suppressor cells in pregnancy complications like preeclampsia, preterm birth, stillbirth, and recurrent spontaneous abortion have been reported. Here, we have summarized the origin, mechanisms, and functions of myeloid-derived suppressor cells during pregnancy along with the recent advancements in this dynamic field. We also shed light on the immunomodulatory activity of myeloid-derived suppressor cells, which can be a foundation for potential therapeutic manipulation in immunological pregnancy complications., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Same Language Subtitling (SLS) of audio-visual content on mainstream TV entertainment to improve mass reading literacy was first conceived and piloted in India. SLS is now being scaled up nationally to ensure that the reading skills of one billion TV viewers, including 600 million weak readers, remain on a lifelong pathway to practice, progress, and proficiency. Will weak readers ignore or try to read along with SLS? Our eye-tracking study investigates this question with 136 weak readers drawn from a remote village in Rajasthan state by showing them popular Hindi film clips of dialog and songs, with and without SLS. We developed an interactive web-based visual analytics tool for exploring eye-tracking data. Based on an analysis of fixations, saccades, and time spent in the subtitle and non-subtitle areas, our main finding is that 70 percent of weak readers engaged in unprompted reading while watching film clips with SLS. We observed that saccadic eye movement is a good indicator to quantify the amount of reading with SLS, and saccadic regression can further differentiate weak readers. Eye-tracking studies of weak readers watching subtitles are rare, and ours may be the first with subjects from rural India., Competing Interests: The author(s) declare(s) that the article's contents are in agreement with the ethics described in http://biblio.unibe.ch/portale/elibrary/BOP/jemr/ethics.html and that there is no conflict of interest regarding the publication of this paper., (Copyright (©) 2022 Somnath Arjun, Brij Kothari, Nirav Kumar Shah, Pradipta Biswas.)

Objective: To assess the efficacy of interruptive electronic alerts in improving adherence to the American Board of Internal Medicine's Choosing Wisely recommendations to reduce unnecessary laboratory testing., Materials and Methods: We administered 5 cluster randomized controlled trials simultaneously, using electronic medical record alerts regarding prostate-specific antigen (PSA) testing, acute sinusitis treatment, vitamin D testing, carotid artery ultrasound screening, and human papillomavirus testing. For each alert, we assigned 5 outpatient clinics to an interruptive alert and 5 were observed as a control. Primary and secondary outcomes were the number of postalert orders per 100 patients at each clinic and number of triggered alerts divided by orders, respectively. Post hoc analysis evaluated whether physicians experiencing interruptive alerts reduced their alert-triggering behaviors., Results: Median postalert orders per 100 patients did not differ significantly between treatment and control groups; absolute median differences ranging from 0.04 to 0.40 for PSA testing. Median alerts per 100 orders did not differ significantly between treatment and control groups; absolute median differences ranged from 0.004 to 0.03. In post hoc analysis, providers receiving alerts regarding PSA testing in men were significantly less likely to trigger additional PSA alerts than those in the control sites (Incidence Rate Ratio 0.12, 95% CI [0.03-0.52])., Discussion: Interruptive point-of-care alerts did not yield detectable changes in the overall rate of undesired orders or the order-to-alert ratio between active and silent sites. Complementary behavioral or educational interventions are likely needed to improve efforts to curb medical overuse., Conclusion: Implementation of interruptive alerts at the time of ordering was not associated with improved adherence to 5 Choosing Wisely guidelines., Trial Registration: NCT02709772., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: None

Purpose: Physical activity is associated with decreased hospitalization during cancer treatment. We hypothesize that activity data can help identify and triage high-risk patients with GI cancer undergoing concurrent chemoradiation., Materials and Methods: This prospective study randomly assigned patients to activity monitoring versus observation. In the intervention arm, a 20% decrease in daily steps or 20% increase in heart rate triggered triage visits to provide supportive care, medication changes, and escalation of care. In the observation group, activity data were recorded but not monitored. The primary objective was to show a 20% increase in triage visits in the intervention group. Secondary objectives were estimating the rates of emergency department (ED) visits and hospitalizations. Crude and adjusted odds ratios were computed using logistic regression modeling., Results: There were 22 patients in the intervention and 18 in the observation group. Baseline patient and treatment characteristics were similar. The primary objective was met, with 3.4 more triage visits in the intervention group than in the observation group (95% CI, 2.10 to 5.50; P < .0001). Twenty-six (65.0%) patients required at least one triage visit, with a higher rate in the intervention arm compared with that in the observation arm (86.4% v 38.9%; odds ratio, 9.95; 95% CI, 2.13 to 46.56; P = .004). There was no statistically significant difference in ED visit (9.1% v 22.2%; P = .38) or hospitalization (4.5% v 16.7%; P = .31)., Conclusion: It is feasible to use activity data to trigger triage visits for symptom management. Further studies are investigating whether automated activity monitoring can assist with early outpatient management to decrease ED visits and hospitalizations., Competing Interests: James M. MetzConsulting or Advisory Role: Varian Medical Systems, IBAResearch Funding: Varian Medical Systems (Inst) Arun GoelEmployment: Flatiron Health (I), Capsule (I)Stock and Other Ownership Interests: Amgen (I), Pfizer (I), Moderna Therapeutics (I), Gilead Sciences (I) Neil K. TaunkHonoraria: Sensus HealthcareConsulting or Advisory Role: Boston Scientific, Indemolecule LLC John N. LukensResearch Funding: Merck (Inst) Abigail T. BermanEmployment: CVS HealthHonoraria: Varian Medical Systems, ImedexConsulting or Advisory Role: AstraZenecaResearch Funding: Merck (Inst)Travel, Accommodations, Expenses: Varian Medical SystemsOpen Payments Link: https://openpaymentsdata.cms.gov/physician/939528 Andrzej P. WojcieszynskiConsulting or Advisory Role: Gerson Lehrman GroupResearch Funding: Philips HealthcareNo other potential conflicts of interest were reported.

Background: Nurse-led education can improve patient satisfaction, and telemedicine has increased patient access during the COVID-19 pandemic., Objectives: The aim of this article was to investigate how nursing telemedicine educational visits influence patient satisfaction., Methods: Patients receiving standard of care in-person education for breast cancer radiation therapy (RT) between January 2019 and June 2019 comprised the preintervention cohort. After July 2019, patients received the same information virtually and represented the postintervention cohort. Press Ganey surveys were used to evaluate patient satisfaction, t tests were performed to differentiate satisfaction scores, and f tests were calculated to determine differences in the variances of response., Findings: Patient satisfaction increased in the postintervention cohort for what to expect during RT, how to manage side effects, and nurses' attentiveness to patient questions and worries. There was decreased variance in patient satisfaction in the postintervention group for quality of care received from nurses and caring manner of nurses.

Background: The Comprehensive Case Management Project (CCMP), was a collaborative implementation research initiative to strengthen malaria early detection and complete treatment in Odisha State, India., Methods: A two-arm quasi-experimental design was deployed across four districts in Odisha, representing a range of malaria endemicity: Bolangir (low), Dhenkanal (moderate), Angul (high), and Kandhamal (hyper). In each district, a control block received routine malaria control measures, whereas a CCMP block received a range of interventions to intensify surveillance, diagnosis, and case management. Impact was evaluated by difference-in-difference (DID) analysis and interrupted time-series (ITS) analysis of monthly blood examination rate (MBER) and monthly parasite index (MPI) over three phases: phase 1 pre-CCMP (2009-2012) phase 2 CCMP intervention (2013-2015), and phase 3 post-CCMP (2016-2017)., Results: During CCMP implementation, adjusting for control blocks, DID and ITS analysis indicated a 25% increase in MBER and a 96% increase in MPI, followed by a -47% decline in MPI post-CCMP, though MBER was maintained. Level changes in MPI between phases 1 and 2 were most marked in Dhenkanal and Angul with increases of 976% and 287%, respectively, but declines in Bolangir (-57%) and Kandhamal (-22%). Between phase 2 and phase 3, despite the MBER remaining relatively constant, substantial decreases in MPI were observed in Dhenkanal (-78%), and Angul (-59%), with a more modest decline in Bolangir (-13%), and an increase in Kandhamal (14%)., Conclusions: Overall, CCMP improved malaria early detection and treatment through the enhancement of the existing network of malaria services which positively impacted case incidence in three districts. In Kandhamal, which is hyperendemic, the impact was not evident. However, in Dhenkanal and Angul, areas of moderate-to-high malaria endemicity, CCMP interventions precipitated a dramatic increase in case detection and a subsequent decline in malaria incidence, particularly in previously difficult-to-reach communities., Competing Interests: The authors have declared that no competing interests exist.

Province-2 is small but densely populated area in the plains of Nepal with 20% of the population on 3% of the land. It is one of the two poorest provinces, with the lowest human and logistic resources. Therefore, there is an enormous and urgent need for improvement of appropriate health care facilities, accessible for all the people. The rural population remains desperately impoverished and to date the provincial and federal governments have lacked the funds to support these needy people. Our work aimed to create a small working model to address the existing problems by establishing the Janakpur Trauma and Orthopaedic Hospital, and ultimately in collaboration with Future Faces, the Craniofacial Centre Nepal, to provide appropriate care at an affordable price to the people in Province-2. This model has been successful, but one of the main challenge remains payments to the health care providers. It is difficult to balance the income and expenditure of hospital services in order to sustain these works and so regular external financial input is required for maintaining continuity of care. It is expected that government agencies and universities such as Madhesh Institute of Health Sciences (MIHS) should be able to educate and assist in the provision of standard care for common illnesses and create suitable human resources to face these challenges., (© 2021 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

Introduction: Maternal immune system tolerance to the semi-allogeneic fetus is critical to a successful pregnancy. We previously reported that myeloid-derived suppressor cells (MDSC) was associated with maternal immune imbalance. T cell immunoglobulin and mucin-containing protein 3 (Tim-3)/Galectin-9 (Gal-9) pathway modulates function of various immune cells in maternal-fetal interface. However, the regulatory effects of Tim-3/Gal-9 signaling on MDSCs and its role in preeclampsia (PE) remain unclear., Methods: In the current study we investigated the expression of Tim-3 on MDSC in preeclampsia (PE) patients to further explore the pathogenesis of PE., Results: The proportion of Tim-3 + M-MDSC (monocytic MDSC) cells was higher in PE patients than in healthy control. Meanwhile, the protein expression of Gal-9, as the ligand of Tim-3, was increased in placenta of PE patients. M-MDSC also expressed a higher level of interferon-γ (IFN-γ) and a lower level of transforming growth factor-β (TGF-β) in PE. Furthermore, our study suggested that blocking Tim-3 could attenuate the inhibitory function of MDSC., Discussion: The abnormal expression of Tim-3 on MDSC might be involved in the pathogenesis of PE, and could be a marker to evaluate the immune function in PE., Competing Interests: Declaration of competing interest All the authors declare that they have no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The management of patients with metastatic cancer is rapidly changing. Historically, radiotherapy was utilized for the treatment of localized disease or for palliation. While systemic therapy remains the mainstay of management for patients with metastatic cancer, radiotherapy is becoming increasingly important not only to palliate symptoms, but also to ablate oligometastatic or oligoprogressive disease and improve local control in the primary site. There is emerging evidence in multiple solid malignancies that patients with low volume metastatic disease that undergo local ablative therapy to metastatic sites may have improved progression free survival and potentially overall survival. In addition, there is increasing evidence that select patients with metastatic disease may benefit from aggressive treatment of the primary site. Patients with metastatic soft tissue sarcoma have a poor overall prognosis. However, there may be opportunities in patients with low volume metastatic soft tissue sarcoma to improve outcomes with local therapy including surgery, ablation, embolization, and radiation therapy. Stereotactic body radiation therapy (SBRT) offers a safe, convenient, precise, and non-invasive option for ablation of sites of metastases. In this review article, we explore the limited yet evolving role of radiotherapy to metastatic and primary sites for local control and palliation, particularly in the oligometastatic setting.

Competing Interests: The authors declare no conflicts of interest.

Purpose: Intracavitary brachytherapy is critical in treatment of cervical cancer with the highest rates of local control and survival. Only about 50% of graduating residents express confidence to develop a brachytherapy practice with caseload as the greatest barrier. We hypothesize that virtual reality (VR)-based intracavitary brachytherapy simulation will improve resident confidence, engagement, and proficiency., Methods: We created a VR training video of an intracavitary brachytherapy case performed by a board-certified gynecologic radiation oncologist and medical physicist. Residents performed a timed intracavitary procedure on a pelvic simulator before and after viewing the VR simulation module on a commercially available VR headset while five objective measures of implant quality were recorded. The residents completed a pre- and postsimulation questionnaire assessing self-confidence, procedural knowledge, and perceived usefulness of the session., Results: There were 14 residents, including five postgraduate year (PGY)-2, three PGY-3, four PGY-4, and two PGY-5, who participated in the VR curriculum. There were improvements in resident confidence (1.43-3.36), and subjective technical skill in assembly (1.57-3.50) and insertion (1.64-3.21) after the simulation. Average time of implant decreased from 5:51 to 3:34 (p = 0.0016). Median technical proficiencies increased from 4/5 to 5/5. Overall, the residents found VR to be a useful learning tool and indicated increased willingness to perform the procedure again., Conclusions: VR intracavitary brachytherapy simulation improves residents' self-confidence, subjective and objective technical skills, and willingness to perform brachytherapy. Furthermore, VR is an immersive, engaging, time-efficient, inexpensive, and enjoyable tool that promotes residents interest in brachytherapy., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

By evolving strains of E. coli that hyper-resist sedimentation, we discovered an uncharacterized mechanism that bacteria can use to remain in suspension indefinitely without expending energy. This unusual phenotype was traced to the anchoring of long colanic acid polymers (CAP) that project from the cell surface. Although each characterized mutant activated this same mechanism, the genes responsible and the strengths of the phenotypes varied. Mutations in rcsC , lpp , igaA, or the yjbEFGH operon were sufficient to stimulate sedimentation resistance, while mutations altering the cps promoter, cdgI, or yjbF provided phenotypic enhancements. The sedimentation resistances changed in response to temperature, growth phase, and carbon source and each mutant exhibited significantly reduced biofilm formation. We discovered that the degree of colony mucoidy exhibited by these mutants was not related to the degree of Rcs pathways activation or to the amount of CAP that was produced; rather, it was related to the fraction of CAP that was shed as a true exopolysaccharide. Therefore, these and other mutations that activate this phenotype are likely to be absent from genetic screens that relied on centrifugation to harvest bacteria. We also found that this anchored CAP form is not linked to LPS cores and may not be attached to the outer membrane. IMPORTANCE Bacteria can partition in aqueous environments between surface-dwelling, planktonic, sedimentary, and biofilm forms. Residence in each location provides an advantage depending on nutritional and environmental stresses and a community of a single species is often observed to be distributed throughout two or more of these niches. Another adaptive strategy is to produce an extracellular capsule, which provides an environmental shield for the microbe and can allow escape from predators and immune systems. We discovered that bacteria can either shed or stably anchor capsules to dramatically alter their propensity to sediment. The degree to which the bacteria anchor their capsule is controlled by a stress sensing system, suggesting that anchoring may be used as an adaptive response to severe environmental challenges., (Copyright © 2021 Kessler et al.)

Carpometacarpal joint dislocations of the hand are exceptional; their diagnosis is sometimes difficult and may go unnoticed especially in a patient with polytrauma. The functional prognosis depends on the precocity of diagnosis and the quality of the reduction and rehabilitation. A successful result has been reported., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Purpose: Definitive chemoradiotherapy represents a standard of care treatment for localized anal cancer. National Comprehensive Cancer Network guidelines recommend radiotherapy (RT) doses of ≥ 45 Gy and escalation to 50.4-59 Gy for advanced disease. Per RTOG 0529, 50.4 Gy was prescribed for early-stage disease (cT1-2N0), and 54 Gy for locally advanced cancers (cT3-T4 and/or node positive). We assessed patterns of care and overall survival (OS) with respect to the RT dose., Methods: The National Cancer Database identified patients with non-metastatic anal squamous cell carcinoma from 2004 to 2015 treated with chemoradiotherapy. Patients were stratified by RT dose: 40-< 45, 45-< 50, 50-54, and > 54-60 Gy. Crude and adjusted hazard ratios (HR) were computed using Cox regression modeling., Results: A total of 10,524 patients were identified with a median follow-up of 40.7 months. The most commonly prescribed RT dose was 54 Gy. On multivariate analysis, RT doses of 40-< 45 Gy were associated with worse OS vs. 50-54 Gy (HR 1.68 [1.40-2.03], P < 0.0001). There was no significant difference in OS for patients who received 45-< 50 or > 54-60 Gy compared with 50-54 Gy. For early-stage disease, there was no significant association between RT dose and OS. For locally advanced disease, 45-< 54 Gy was associated with worse survival vs. 54 Gy (HR 1.18 [1.04-1.34], P = 0.009), but no significant difference was detected comparing > 54-60 Gy vs. 54 Gy (HR 1.08 [0.97-1.22], P = 0.166)., Conclusions: For patients with localized anal cancer, RT doses of ≥ 45 Gy were associated with improved OS. For locally advanced disease, 54 Gy but not > 54 Gy was associated with improved OS.

There is an increasing trend of developing various low-cost grafted natural amino polysaccharides for the biosorptive removal of noxious dye effluents like Malachite green (MG) and anionic Reactive Red-195 (RR-195) dyes from aqueous solution. Chemically cross-linked chitosan microsphere (CTS-HMP), a promising non-toxic biosorbent possessing high charge density and thermal stability was prepared by using hexametaphosphate as ionic cross-linker. Batch biosorption experiments were carried out under different temperatures (298, 308 and 318 K), pH (2.0-10.0), initial concentrations (25-250 mg L -1 ), adsorbent dosage (0.01-0.1 g) and contact times (0-180 min) to understand the optimum experimental conditions and simultaneously evaluate the adsorption isotherms and kinetics of CTS-HMP. Biosorption equilibrium was established in 120 and 60 min for MG and RR-195 removal process. The pseudo-equilibrium process was best described by the pseudo-second-order kinetic (R 2  ≥ 0.98), Freundlich and Temkin isotherm model (R 2  ≥ 0.90). The removal rate of MG and RR-195 gradually increased (69.40 and 148 mg g -1 ) at 250 mg L -1 of initial concentration till 100 and 50 min of contact period in a single contaminant system, though the removal efficiency of acid dye was ~2 times higher compared to basic dye under optimum conditions (p < 0.05; t-test). Thermodynamic parameters indicated exothermic (MG) and endothermic (RR-195) nature of spontaneous dye removal. The activation energy of sorption (E a ) was <50 kJ mol -1 which highlighted the importance of physical adsorption process. Therefore, the obtained results clearly validate the sustainable utilization of CTS-HMP as a promising functionalized chitosan microparticles/agent for removing dye effluents from the contaminated aqueous phase., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Early-stage glottic laryngeal cancer is treated with surgery or radiotherapy (RT), but limited randomized data exists to support one modality over the other. This study evaluates survival differences in early glottic cancer patients treated with either surgery or RT., Materials and Methods: 14,498 patients with early glottic cancer diagnosed from 2004 to 2015 and treated with surgery or RT were identified in the National Cancer Database. Kaplan-Meier method was used to analyze differences in overall survival (OS) by treatment (surgery vs. RT) and radiation dose fractionation. Cox regression modeling and propensity score-matched (PSM) analysis were performed. Adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI) were computed., Results: Median follow-up and median OS for all patients were 49.5 and 118 months, respectively. The estimated 5-year OS for surgery and RT was 77.5% and 72.6%, respectively (P < 0.0001). On multivariate analysis, aHR (95% CI) for surgery compared to RT was 0.87 (0.81-0.94, P = 0.0004). Compared to RT regimen 63-67.5 Gray (Gy) in 28-30 fractions, worse survival was noted for RT regimen 66-70 Gy in 33-35 fractions (aHR 1.15, 95% CI 1.07-1.23, P = 0.0003). When compared with hypofractionated RT (63-67.5 Gy in 28-30 fractions), patients undergoing surgery no longer showed improved OS (aHR 0.94, 95% CI 0.86-1.02, P = 0.154). The finding was confirmed on PSM analysis (surgery aHR 0.95, 95% CI 0.87-1.05, P = 0.322)., Conclusion: In early glottic tumors, patients treated with surgery demonstrated improved survival compared to RT, but when hypofractionation was considered, there were no significant differences in OS between patients undergoing surgery or RT., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This study evaluates the effect of preeclampsia on body mass index (BMI) of offspring who were exposed to preeclampsia in utero., Methods: Data were obtained from studies identified by a literature search in electronic databases. Random-effects metanalyses were conducted to achieve mean difference in BMI, waist circumference, gestation length, and birthweight between preeclampsia exposed (PE) and non-exposed (non-PE) offspring older than 5 years. Metaregression analyses were performed to identify factors affecting offspring BMI., Results: Sixteen studies (11639 PE offspring; age 15.5 years [14.2, 16.8]; 33.3% [32.6, 33.9] males vs 526,576 non-PE offspring; age 15.7 years [15.0, 16.4]; 42.6% [40.6, 44.5] male) were used. Gestation duration and birthweight of PE fetuses were significantly lesser than those of non-PE fetuses (mean difference (MD) -0.66 weeks [-1.25, -0.07]; p = 0.03 and MD -207.9 [-344.0, -71.8]; p = 0.003) respectively. BMI of PE offspring was significantly higher than non-PE offspring (MD 0.54 kg/m 2 [0.27, 0.82]; p = 0.0001). Odds of being obese was significantly higher in PE than non-PE offspring (odds ratio 2.12 [1.70, 2.66]; P < 0.00001). Waist circumference was also significantly higher in PE than in non-PE offspring (MD 1.37 cm [0.67, 2.06]; p = 0.0001). Offspring BMI was significantly inversely associated with maternal age in both PE and non-PE groups., Conclusion: Preeclampsia poses risk of higher BMI and waist circumference especially to the offspring of older mothers., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To design and characterize aerosol microparticles (MP) to provide sustained release of the water-soluble compound sulforhodamine B (SRB) and achieve effective aerosol dispersion. Significance: Modulating the release of water-soluble compounds remains a challenge in pulmonary drug delivery. Methods: SRB and water made up an aqueous solution, while acetalated dextran (Ac-Dex) and isopropyl alcohol made up an organic solution. The two solutions were mixed together, and the solution was spray dried to produce MP. MP were characterized for morphology, size, release kinetics, aerosol dispersion, and cellular interactions. Results: Ac-Dex MP exhibited corrugated morphology and aerodynamic diameters from 2.06 to 2.86 μm. MP deposited in all stages of a Next Generation Impactor, with >90% fine particle fraction. MP exhibited encapsulation efficiencies >129% with SRB loading values up to 16.7 μg SRB/mg MP. MP exhibited sustained release of SRB at pH 7 and fast release at pH 5. In vitro experiments showed minimal cytotoxicity, successful uptake of MP in epithelial cells, and no disruption to the integrity of epithelial monolayers. Conclusions: Ac-Dex MP systems demonstrated the ability to provide sustained the release of a water-soluble therapeutic in addition to effective aerosol dispersion for pulmonary applications.

Objective: To determine the optimal sequencing of chemoradiotherapy for locally advanced laryngeal cancer. The hypothesis was that concurrent chemoradiotherapy (CCRT) would be associated with improved overall survival (OS) compared to induction chemotherapy followed by radiotherapy (RT)/surgery (IC)., Methods: The National Cancer Database identified 8,154 patients with American Joint Commission on Cancer stage III/IV (excluding T1) laryngeal cancer between 2004 and 2013 treated with one of the established organ preservation techniques: CCRT or IC. The association between OS and total radiation dose (< 66 gray [Gy] or ≥ 66 Gy) was analyzed using the Kaplan-Meier method, as was the association between OS and timing of IC (21-42, 43-100, or 101-120 days before RT). Hazard ratios (HR) adjusted for patient and clinical characteristics were computed using Cox regression modeling., Results: The median follow-up was 32.7 months. The estimated 5-year OS for CCRT and IC was 49.9% and 50.6%, respectively (P = 0.653). On multivariate analysis, no difference was observed between the two regimens (IC, adjusted HR 0.96, 95% confidence interval [CI] 0.88-1.04, P = 0.268). Radiation dose ≥66 Gy had improved OS overall in CCRT group but not in IC patients. When comparing CCRT and IC in patients receiving ≥66 Gy, there was no difference in OS (adjusted HR 0.97, 95% CI 0.89-1.06, P = 0.552). Patients starting chemotherapy 21 to 42 or 101 to 120 days prior to RT had inferior OS compared to patients starting between 43 to 100 days., Conclusion: For locally advanced laryngeal cancer, there is no difference in OS between CCRT and IC. Factors associated with survival included radiation dose and timing of induction chemotherapy before RT., Level of Evidence: 3b Laryngoscope, 129:2313-2320, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Metformin (Met) has been found to modify the methylation of H19 and to alter its expression. In addition, IL-27, one of the downstream factors in the H19 signaling pathway, plays an important role in the pathogenesis of pre-eclampsia (PE). In this study, we investigated the molecular mechanism underlying the therapeutic effect of Met in the management of PE both in vivo and in vitro. The role of H19 signaling pathway in PE was validated using online bioinformatics tools, luciferase assays, real-time PCR and Western Blot. A tail-cuff method was used to examine the blood pressures in PE rats with or without Met treatment. Cells exhibited a dose-dependent increase of H19 methylation, which inhibited the expression of H19. Additionally, upon the Met treatment, levels of miR-148-5p and miR-216-3p were both elevated in a dose-dependent manner while levels of p28 mRNA and EBI3 mRNA were both inhibited by Met treatment. Also, H19 was found to regulate the expression of miR-148a-5p and miR-216-3p, while P28 and EBI3 were respectively identified as target genes of miR-148a-5p and miR-216-3p. Therefore, the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways were implicated in the pathogenesis of PE. Met was implicated in the pathogenesis of PE via modulating the H19 signaling pathway. The methylation of H19 reduced H19 expression, which in turn could up-regulate the expression of miR-148-5p/miR-216-3p. And the expressions of subunits of IL-27, P28 and EBI3, were thus suppressed. Therefore, Met-induced inhibition of H19 also led to the reduction of IL-27 expression, TNF-α and IL-6 in vivo., (Copyright © 2019. Published by Elsevier B.V.)