Efficient synthesis of CRISPR-Cas13a-antimicrobial capsids against MRSA facilitated by silent mutation incorporation.

In response to the escalating global threat of antimicrobial resistance, our laboratory has established a phagemid packaging system for the generation of CRISPR-Cas13a-antimicrobial capsids targeting methicillin-resistant Staphylococcus aureus (MRSA). However, a significant challenge arose during the packaging process: the unintentional production of wild-type phages alongside the antimicrobial capsids. To address this issue, the phagemid packaging system was optimized by strategically incorporated silent mutations. This approach effectively minimized contamination risks without compromising packaging efficiency. The study identified the indispensable role of phage packaging genes, particularly terL-terS, in efficient phagemid packaging. Additionally, the elimination of homologous sequences between the phagemid and wild-type phage genome was crucial in preventing wild-type phage contamination. The optimized phagemid-LSAB(mosaic) demonstrated sequence-specific killing, efficiently eliminating MRSA strains carrying target antibiotic-resistant genes. While acknowledging the need for further exploration across bacterial species and in vivo validation, this refined phagemid packaging system offers a valuable advancement in the development of CRISPR-Cas13a-based antimicrobials, shedding light on potential solutions in the ongoing battle against bacterial infections.

Pancreatic Tuberculosis With Duodenal Fistula Presenting as Life-Threatening Gastrointestinal Bleeding.

Pancreatic tuberculosis (TB) warrants heightened suspicion in individuals with pancreatic lesions and risk factors such as HIV, organ transplantation, or pertinent immigration history. We present a 38-year-old man who presented with hemodynamically unstable gastrointestinal bleeding. He was found to have pancreatic TB complicated by a duodenal ulcer with fistula. Following 1 month of antitubercular therapy, he experienced complete resolution of symptoms, healing of the duodenal ulcer, closure of the fistulous tract, and a decrease in the size of the pancreatic lesion as observed on imaging. Our case highlights the importance of early diagnosis and treatment of pancreatic TB.

Reimagining gendered community interventions: the case of family planning programs in rural Bangladesh.

Family planning programs in Bangladesh have been successfully operating for over half a century, achieving phenomenal reductions in fertility rates. Acknowledging restrictions on women's freedoms, much of the initial program design was concentrated on giving household supplies for women priority. However, one unfortunate impact of these outreach services is that, by bypassing the opportunity to challenge patriarchal attitudes directly, they inadvertently reinforce the power relationships of the status quo. Hence, we problematise the decision-making structures within Bangladesh's family planning programs. We argue that the fundamental flaw with Bangladesh's family planning program is the lack of conscious effort to understand women's health choices and decision-making as a complex contextual process of relational, structural, and institutional forces. Additionally, avoiding men in these programs often creates new dependencies for women, as this approach does not directly seek to build relational bridges based on equality between genders. As a result, many women still depend on permission from their husbands and family for reproductive health services and face constrained family planning choices and access to care. We recommend that family planning programs adopt a broader vision to create new and more sustainable possibilities in an ever-evolving social relations landscape where gender is constantly negotiated. Such strategies are even more pressing in the post-Covid world, as national systems are exposed to uncertainty and ambiguity.

Purplish Discoloration of Urine in a Patient Receiving Cefiderocol: A Rare Adverse Effect.

Drug-induced urine discoloration, although usually benign, can still raise concern in healthcare facilities. This case report presents the second case of purple urine discoloration associated with cefiderocol in a 64-year-old male admitted to the intensive care unit for ventilator-associated pneumonia. The patient required broad-spectrum antibiotic treatment with vancomycin, cefiderocol, amikacin, and micafungin. On the fourth day after initiating antibiotics, the presence of purplish urine in the foley bag was noted. Urinalysis showed 11-25 red blood cells/hpf, but cultures ruled out urinary tract infection. Further laboratory workup did not reveal any evidence of hemolysis or rhabdomyolysis. Cultures from the endotracheal aspirate grew multidrug-resistant Pseudomonas. Cefiderocol and amikacin were continued to complete a seven-day course. Two days after completion of the cefiderocol course, the urine discoloration cleared up, providing strong evidence that cefiderocol was the cause of the discoloration.

The Association Between Onset of Staphylococcal Non-menstrual Toxic Shock Syndrome With Inducibility of Toxic Shock Syndrome Toxin-1 Production.

Non-menstrual toxic shock syndrome (non-mTSS) is a life-threatening disease caused by Staphylococcus aureus strains producing superantigens, such as staphylococcal enterotoxins A, B, C, and toxic shock syndrome toxin-1 (TSST-1). However, little is known about why the TSS cases are rare, although S. aureus strains frequently carry a tst gene, which encodes TSST-1. To answer this question, the amount of TSST-1 produced by 541 clinical isolates was measured in both the presence and absence of serum supplementation to growth media. Then a set of S. aureus strains with similar genetic backgrounds isolated from patients presenting with non-mTSS and those with clinical manifestations other than non-mTSS was compared for their TSST-1 inducibility by human serum, and their whole-genome sequences were determined. Subsequently, the association of mutations identified in the tst promoter of non-mTSS strains with TSST-1 inducibility by human serum was evaluated by constructing promoter replacement mutants and green fluorescent protein (GFP) reporter recombinants. Results showed that 39 out of 541 clinical isolates (7.2%), including strains isolated from non-mTSS patients, had enhanced production of TSST-1 in the presence of serum. TSST-1 inducibility by human serum was more clearly seen in non-mTSS strains of clonal complex (CC)-5. Moreover, the whole-genome sequence analysis identified a set of sequence variations at a putative SarA-binding site of the tst promoter. This sequence variation was proven to be partially responsible for the induction of TSST-1 production by human serum. We conclude that the onset of staphylococcal toxic shock syndrome caused by TSST-1-producing CC-5 strains seem at least partially initiated by serum induction of TSST-1, which is regulated by the mutation of putative SarA-binding site at the tst promoter.

Caffeine-Induced Severe Erosive Esophagitis.

Caffeine is one of the most frequently used stimulants worldwide. It is, therefore, subject to frequent intentional and unintentional misuse. However, severe erosive esophagitis due to acute caffeine overdose is extremely rare. We report the case of a 43-year-old male with a past medical history of paranoid schizophrenia admitted to our hospital with esophageal symptoms (throat pain, retrosternal chest pain, dysphagia/odynophagia, nausea, and vomiting) two days after ingesting a bottle of caffeine pills containing about 30 g of caffeine in a suicide attempt. He was found to have rhabdomyolysis and acute renal failure warranting hemodialysis. Esophagogastroduodenoscopy done due to persistent retrosternal chest pain, dysphagia, odynophagia, and nausea despite being on oral famotidine 20 mg daily revealed severe erosive esophagitis. This case highlights the risk of concurrent renal and gastrointestinal injuries after acute ingestion of an excessive amount of caffeine tablets. Our experience suggests that in patients of caffeine overdose with persistent esophageal symptoms such as odynophagia, dysphagia, and retrosternal chest pain, endoscopic evaluation is advisable to rule out drug-induced esophagitis.

Brevibacterium Bacteremia in the Setting of Pyogenic Liver Abscess: A Case Report with Accompanying Literature Review.

A 71-year-old Pakistani man with poorly controlled type 2 diabetes mellitus presenting with worsening mental status, abdominal pain, and oral intake for the past seven days was found to have pyogenic hepatic abscess with unculturable bacteria and subsequently found to have rare Brevibacterium bacteremia.

Purulent Proctitis Caused by Prevotella bivia in a Homosexual Male.

A 32-year-old homosexual male presented with suprapubic pain. Computed tomography showed rectal wall thickening. Flexible sigmoidoscopy showed small pockets of pus that were opened with mucosal biopsies, and additional pus was diffusely expressed from the rectal wall by applying blunt pressure with the biopsy forceps. Cultures from the pus grew Prevotella bivia. Symptoms resolved after treatment with doxycycline and metronidazole. Proctitis due to P. bivia was not previously reported.

Time series analysis of Japanese encephalitis and weather in Linyi City, China.

OBJECTIVES: To examine the relationship between meteorological factors and epidemiological pattern of Japanese encephalitis in Linyi City during 1956-2004. METHODS: Autoregressive integrated moving average (ARIMA) models were used to evaluate the relationship between monthly JE incidence and weather factors. Logarithmic transformation was applied to the JE incidence series to assure the normality and homogeneity of variance of the residuals. The effect of mass vaccination on JE incidence was also evaluated using a transfer function in the time series analysis. RESULTS: The analysis suggested that monthly average temperature [ß = 0.0574, 95% confidence interval (CI) = (0.0172, 0.0976)] and relative humidity [ß = 0.0082, 95% CI = (0.0004, 0.0158)] were positively associated with the logarithmic incidence of Japanese encephalitis after adjusting for mass vaccination in this area. CONCLUSIONS: Weather variables might be treated as possible predictors of Japanese encephalitis incidence for regions with similar geographic, weather, and socio-economic conditions to Linyi, China.

Increasing trend of primary NO(2) exhaust emission fraction in Hong Kong.

Despite the successful reduction in roadside NO( x ) levels, no such decrease has been detected in roadside NO(2) concentration in Hong Kong. One underlying cause could be the rising primary NO(2) fraction of the total emission of NO( x ). Primary NO(2) can be particularly detrimental to Hong Kong because a large fraction of the population are exposed to the traffic-related primary pollutants in the street canyons formed by congested high-rise buildings. In this study, hourly mean concentration data for roadside nitrogen oxides (NO( x )), nitrogen dioxide (NO(2)), and background ozone (O(3)) were used to estimate the mean primary NO(2) fraction from vehicle exhausts in Hong Kong. An overall increasing trend was observed for the primary NO(2) fraction (f-NO(2)) values in all the three roadside air monitoring sites. The primary NO(2) as a fraction of total NO( x ) (f-NO(2)) increased approximately from 2% in 1998 to 13% in 2008 in Hong Kong. The two particular periods of rising f-NO(2) coincided with the two implementation periods of the diesel retrofit programs for the light-duty vehicles and heavy-duty vehicles. Future vehicle emission control strategies should target not only total NO( x ) but also primary NO(2). Health benefit or disease burden estimates should be taken into account and updated in the process of policy planning and evaluation.

Carcinoid tumors and small-cell carcinomas of the gallbladder and extrahepatic bile ducts: a comparative study based on 221 cases from the Surveillance, Epidemiology, and End Results Program.

Primary neuroendocrine tumors of the gallbladder (GB) and extrahepatic biliary ducts (EHBDs) include carcinoid tumors and small-cell carcinomas (SCCs). They are uncommon, and therefore, little is known about their demographics and clinical course. From National Cancer Institute's Surveillance, Epidemiology, and End Results program (1973-2005), we analyzed the demographics and 10-year relative survival rates of carcinoids and SCCs of the GB and EHBD according to histologic type and stage. There were 119 cases of carcinoid tumors and 54 cases of SCCs in the GB. There were 31 carcinoid tumors and 17 SCCs in the EHBD. The female/male ratios of carcinoids in the GB and EHBD were 2.4 and 1.6, respectively. The ratios for SCC in the GB and EHBD were 2.2 and 1.1, respectively. For the GB, the mean age of diagnosis for carcinoids was 64.5, and for SCC, it was 67.5. For the EHBD, the mean age was 58.2 for carcinoids and 68.4 for SCC. The 10-year survival rates were 36% for carcinoid tumors of the GB and 80% for carcinoid tumors of the EHBD. For SCC, the 10-year survival was 0% in the GB and EHBD. Carcinoid tumors and SCC of the extrahepatic biliary tree are uncommon neoplasms that differ in their demographics and biologic behavior, supporting the distinction of these 2 histopathologic types. Therefore, these tumors should be separately classified and not included in the single generic group of neuroendocrine carcinoma.