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Here, we present a case report of a healthy Asian woman with no past medical history presenting with severe acute liver injury associated with ingestion of kombucha. We also discuss the active ingredients in kombucha and the evidence behind its efficacy. This case emphasizes that although herbal teas have been proposed to have numerous health benefits, much is unknown about the amount that can be safely ingested.

Streptococcus halichoeri is a relatively newly identified species of pyogenic streptococci that causes zoonotic infection in humans. S. halichoeri was first described in 2004 as indigenous to seals, and only 8 reports of human S. halichoeri infection have been published. S. halichoeri grows as small, white, nonhemolytic colonies and may be strongly catalase-positive on routine blood agar media, which can lead to isolates being misidentified as coagulase-negative staphylococci. S. halichoeri tests positive for Lancefield group B antigen, like S. agalactiae, but can be identified with matrix-assisted laser desorption/ionization time of flight mass spectrometry or partial 16S rRNA sequencing. We describe 3 cases of S. halichoeri bone and joint infections in patients in the United States with underlying health conditions. In addition, we examine the microbiologic characteristics of S. halichoeri and discuss the importance of fully identifying this organism that might otherwise be disregarded as a skin commensal.

Abstract Antibiotic resistance is a serious public health problem throughout the world. Overcoming methicillin and multidrug-resistant Staphylococcus aureus (MRSA/MDRSA) infections has become a challenge and there is an urgent need for new therapeutic approaches. We have previously demonstrated that the endocannabinoid Anandamide (AEA) can sensitize MRSA to antibiotics. Here we have studied the mechanism of action using a MDRSA clinical isolate that are sensitized by AEA to methicillin and norfloxacin. We found that AEA treatment halts the growth of both antibiotic-sensitive and antibiotic-resistant S. aureus. The AEA-treated bacteria become elongated and the membranes become ruffled with many protrusions. AEA treatment also leads to an increase in the percentage of bacteria having a complete septum, suggesting that the cell division is halted at this stage. The latter is supported by cell cycle analysis that shows an accumulation of bacteria in the G2/M phase after AEA treatment. We further observed that AEA causes a dose-dependent membrane depolarization that is partly relieved upon time. Nile red staining of the bacterial membranes indicates that AEA alters the membrane structures. Importantly, 4′-6-diamidino-2-phenylindole (DAPI) accumulation assay and ethidium bromide efflux (EtBr) assay unveiled that AEA leads to a dose-dependent drug accumulation by inhibiting drug efflux. In conclusion, our study demonstrates that AEA interferes with cell division, alters the membrane properties of MDRSA, and leads to increased intracellular drug retention, which can contribute to the sensitization of MDRSA to antibiotics.

Objective: We report a case of pituitary apoplexy (PA) with negative radiographic findings for PA and cerebrospinal fluid (CSF) analysis consistent with neutrophilic meningitis. PA is a rare endocrinopathy requiring prompt diagnosis and treatment. Presentation with acute neutrophilic meningitis is uncommon. Methods: The diagnostic modalities included pituitary function tests (adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, prolactin), brain computed tomography and magnetic resonance imaging (MRI), and CSF analysis. Results: A 67-year-old man presented with worsening headache, nausea, and retching. He was somnolent with an overall normal neurologic examination other than a peripheral vision defect in the left eye. MRI showed a pituitary mass bulging into the suprasellar cistern with optic chiasm elevation, consistent with pituitary macroadenoma. Laboratory evaluation revealed decreased levels of adrenocorticotropic hormone, random cortisol, thyroid-stimulating hormone, thyroxine, luteinizing hormone, and testosterone. He had worsening encephalopathy with left eye ptosis and decreased vision, prompting a repeat computed tomography and MRI, showing no interval change in the pituitary adenoma or evidence of bleeding. CSF analysis revealed a leukocyte count of 1106/mm3 (89% neutrophils), a total protein level of 138 mg/dL, red blood cell count of 2040/mm3 without xanthochromia, and glucose level of 130 mg/dL. The CSF culture result was negative. Transsphenoidal resection revealed a necrotic pituitary adenoma with apoplexy. Conclusions: Including PA in the differential diagnosis of acute headache is important, particularly in patients with visual disturbances. PA can present with sterile meningitis, mimicking acute bacterial meningitis. While neuroimaging can help detect PA, the diagnosis of PA remains largely clinical.

A 70-year-old woman presented with aphasia caused by acute infarction in the left middle cerebral artery. Cardiac investigation revealed progressively increasing mobile mass in the left atrial appendage over 2 months (from 9 to 15 mm). Decision was made to proceed with mass resection, and pathological evaluation confirmed Masson tumor. (Level of Difficulty: Advanced.)

A 53-year-old female patient presented for evaluation of a murmur. The examination revealed a 2/6 systolic ejection murmur in the left upper sternal border. Transthoracic echocardiography with color Doppler showed increased blood flow around the apex of the right ventricle. Further imaging revealed the right coronary artery emerging from the pulmonary artery. (Level of Difficulty: Beginner.)

Background. It has been confirmed that bacterial biofilm covering dental implants is the main microbial source causing preimplant infectious and inflammatory diseases. The purpose of this study was to evaluate the antibacterial/antibiofilm effect of chlorhexidine, incorporated into a sustained-release varnish of chlorhexidine (SRV-CHX) coating, on dental abutments. Materials and Methods. Three kinds of dental abutments were used: a high-performance semi-crystalline engineering thermoplastic polyetheretherketone (PEAK) healing abutment, a titanium healing abutment, and a titanium permanent abutment. These abutments were coated with SRV-CHX or SRV-placebo and exposed daily to fresh cultures of Streptococcus mutans. The effect of SRV-CHX on S. mutans growth on agar plates was studied by measuring the zone of inhibition (ZOI) around each tested abutment every day for a period of 36 days. Biofilm formation on the SRV-CHX/placebo-coated abutments was detected using confocal laser scanning microscopy (CLSM) and high-resolution scanning electron microscopy (HR-SEM), energy dispersive X-ray analysis (EDX), and monitored by crystal violet (CV) staining. Results. SRV-CHX-coated abutments 2 and 3 were able to inhibit S. mutans growth for 34 days, while abutment 1 inhibited growth for 32 days. Abutment-associated biofilm formation was notably inhibited by SRV-CHX coating after 13 days of incubation with S. mutans. Finally, the biofilm formed around SRV-CHX-coated abutments was completely inhibited up to 12 days of abutment exposure to S. mutans. Conclusion. Coating of dental abutments with SRV-CHX demonstrated long-term effective inhibition of S. mutans growth and biofilm formation on the abutment surface.

Streptococcus mutans is a Gram-positive bacterium highly associated with dental caries, and it has a strong biofilm-forming ability, especially in a sugar-rich environment. Many strategies have been undertaken to prevent dental caries by targeting these bacteria. Recently, we observed that a sustained-release varnish containing triclosan and cannabidiol (CBD) was more efficient than each compound alone in preventing biofilm formation by the fungus Candida albicans, which is frequently involved in oral infections together with S. mutans. It was therefore inquiring to study the effect of this drug combination on S. mutans. We observed that the combined treatment of triclosan and CBD had stronger anti-bacterial and anti-biofilm activity than each compound alone, thus enabling the use of lower concentrations of each drug to achieve the desired effect. The combined drug treatment led to an increase in the SYTO 9low, propidium iodide (PI)high bacterial population as analyzed by flow cytometry, indicative for bacteria with disrupted membrane. Both triclosan and CBD induced membrane hyperpolarization, although there was no additive effect on this parameter. HR-SEM images of CBD-treated bacteria show the appearance of elongated and swollen bacteria with several irregular septa structures, and upon combined treatment with triclosan, the bacteria took on a swollen ellipse and sometimes oval morphology. Increased biofilm formation was observed at sub-MIC concentrations of each compound alone, while combining the drugs at these sub-MIC concentrations, the biofilm formation was prevented. The inhibition of biofilm formation was confirmed by CV biomass staining, MTT metabolic activity, HR-SEM and live/dead together with exopolysaccharide (EPS) staining visualized by spinning disk confocal microscopy. Importantly, the concentrations required for the anti-bacterial and anti-biofilm activities toward S. mutans were non-toxic to the normal Vero epithelial cells. In conclusion, the data obtained in this study propose a beneficial role of combined triclosan/CBD treatment for potential protection against dental caries.

Candida albicans is a common fungal pathogen. Biofilm formation on various surfaces is an important determinant of C. albicans pathogenicity. Our previous results demonstrated the high potential of cannabidiol (CBD) to affect C. albicans biofilms. Based on these data, we investigated the possibility of incorporating CBD and/or triclosan (an antimicrobial agent that is widely utilized in dentistry) in a sustained-release varnish (SRV) (SRV-CBD, SRV-triclosan) to increase their pharmaceutical potential against C. albicans biofilm, as well as that of the mixture of the agents into SRV (SRV-CBD/triclosan). The study was conducted in a plastic model, on agar, and in an ex vivo tooth model. Our results demonstrated strong antibiofilm activity of SRV-CBD and SRV-triclosan against C. albicans in all tested models. Both formulations were able to inhibit biofilm formation and to remove mature fungal biofilm. In addition, SRV-CBD and SRV-triclosan altered C. albicans morphology. Finally, we observed a dramatic enhancement of antibiofilm activity when combined SRV-CBD/triclosan was applied. In conclusion, we propose that incorporation of CBD or triclosan into SRV is an effective strategy to fight fungal biofilms. Importantly, the data demonstrate that our CBD/triclosan varnish is safe, and is not cytotoxic for normal mammalian cells. Furthermore, we propose that CBD and triclosan being in mixture in SRV exhibit complementary antibiofilm activity, and thus can be explored for further development as a potential treatment against fungal infections.

Infections caused by antibiotic-resistant strains of Staphylococcus aureus have reached epidemic proportions globally. Our previous study showed antimicrobial effects of anandamide (AEA) and arachidonoyl serine (AraS) against methicillin (MET)-resistant S. aureus (MRSA) strains, proposing the therapeutic potential of these endocannabinoid/endocannabinoid-like (EC/EC-like) agents for the treatment of MRSA. Here, we investigated the potential synergism of combinations of AEA and AraS with different types of antibiotics against MRSA grown under planktonic growth or biofilm formation. The most effective combinations under planktonic conditions were mixtures of AEA and ampicillin (AMP), and of AraS and gentamicin (GEN). The combination with the highest synergy in the biofilm formation against all tested bacterial strains was AEA and MET. Moreover, the combination of AraS and MET synergistically caused default of biofilm formation. Slime production of MRSA was also dramatically impaired by AEA or AraS combined with MET. Our data suggest the novel potential activity of combinations of EC/EC-like agents and antibiotics in the prevention of MRSA biofilm formation.

Extraosseous Ewing’s sarcoma is a rare and aggressive malignant tumor with a poor prognosis. The pancreas is an extremely uncommon primary site, with only 27 cases that have been published worldwide. We report a 26-year-old female who presented with 5 days of left upper quadrant pain, nausea, and vomiting. On examination, she was anicteric and had epigastric and left upper quadrant tenderness without guarding, rebound tenderness, or a palpable mass. She had slightly elevated serum aminotransferase and lipase levels. Abdominal computerized tomography revealed a multilobulated tumor arising from the body and tail of the pancreas. A biopsy confirmed a small round cell tumor, and immunohistochemistry was positive for CD99 in approximately 70% of the tumor cells. A fluorescence in situ hybridization (FISH) assay showed a 22q12 rearrangement. She was diagnosed with extraosseous Ewing sarcoma of the pancreas and underwent multiagent neoadjuvant chemotherapy followed by surgical resection, but subsequent imaging revealed evidence of systemic disease progression. She chose to go on hospice care and died a few weeks later.

Aim. To assess the effect of treating chronic hepatitis C virus (HCV) infection with direct acting antiviral drugs (DAAs) on glycemic control in patients with concomitant diabetes mellitus (DM). Methods. We performed a retrospective case-control study in a viral hepatitis ambulatory clinic in Shreveport, Louisiana, during the period 11/01/2014 to 12/31/2017. All the clinic patient ages 18 years and above with treatment-naïve/biopsy-proven chronic hepatitis C and DM (hemoglobin A1C level≥6.5%) who were eligible for treatment were included in the study. Of 118 such patients, 59 were treated with oral DAAs for 8-12 weeks with the goal of achieving a sustained virologic response (SVR). A control group of 59 patients did not receive treatment for their hepatitis C and was followed in the clinic. Patients in the control group did not receive treatment either due to insurance issues or refusal of hepatitis C treatment. Results. Fifty-five of the 59 patients treated with DAAs (93%) achieved a SVR. Six months after treatment completion, their mean±SEM HbA1C level had decreased by 1.1±0.03% (P

Drug-associated thrombocytopenia is often unrecognized. We report a 76-year-old female with lymphoma who presented with easy bruising and oral bleeding. She had undergone screening for hepatitis B virus (HBV) prior to starting rituximab and was found to have hepatitis B core serum antibody (IgG anti-HBc). She was therefore treated with prophylactic entecavir 0.5 mg daily to prevent reactivation of HBV. Her initial platelet count was 136,000/mm3. Five days after starting entecavir, she presented with bruising and oral bleeding and was found to have a platelet count of 7,000/mm3. A coagulation profile and the rest of the blood parameters (RBC and WBC counts) were normal. Entecavir was stopped, and she was given 3 units of apheresed platelets followed by intravenous immunoglobulin (1 g/kg) for 5 consecutive days. Her platelet counts improved and normalized in one week. She was diagnosed with entecavir-induced thrombocytopenia based on the temporal relationship and after carefully excluding alternate causes of thrombocytopenia. This case highlights the importance of recognizing drug-induced thrombocytopenia (DITP) as a reversible cause of thrombocytopenia.

Balamuthia mandrillaris is a rare cause of granulomatous meningoencephalitis associated with high mortality. We report a 69-year-old Caucasian female who presented with a 3-day history of worsening confusion and difficulty with speech. On admission, she was disoriented and had expressive dysphasia. Motor examination revealed a right arm pronator drift. Cerebellar examination showed slowing of finger-nose testing on the left. She was HIV-negative, but the absolute CD4 count was low. Neuroimaging showed three cavitary, peripherally enhancing brain lesions, involving the right frontal lobe, the left basal ganglia, and the left cerebellar hemisphere. She underwent right frontal craniotomy with removal of tan, creamy, partially liquefied necrotic material from the brain, consistent with granulomatous amoebic encephalitis on tissue staining. Immunohistochemical studies and PCR tests confirmed infection with Balamuthia mandrillaris. She was started on pentamidine, sulfadiazine, azithromycin, fluconazole, flucytosine, and miltefosine. The postoperative course was complicated by an ischemic stroke, and she died a few weeks later.

Candida albicans is a common fungal pathogen in humans. Biofilm formation is an important virulence factor of C. albicans infections. We investigated the ability of the plant-derived cannabidiol (CBD) to inhibit the formation and removal of fungal biofilms. Further, we evaluated its mode of action. Our findings demonstrate that CBD exerts pronounced time-dependent inhibitory effects on biofilm formation as well as disruption of mature biofilm at a concentration range below minimal inhibitory and fungicidal concentrations. CBD acts at several levels. It modifies the architecture of fungal biofilm by reducing its thickness and exopolysaccharide (EPS) production accompanied by downregulation of genes involved in EPS synthesis. It alters the fungal morphology that correlated with upregulation of yeast-associated genes and downregulation of hyphae-specific genes. Importantly, it represses the expression of C. albicans virulence-associated genes. In addition, CBD increases ROS production, reduces the intracellular ATP levels, induces mitochondrial membrane hyperpolarization, modifies the cell wall, and increases the plasma membrane permeability. In conclusion, we propose that CBD exerts its activity towards C. albicans biofilm through a multi-target mode of action, which differs from common antimycotic agents, and thus can be explored for further development as an alternative treatment against fungal infections.

Background: Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) are two major contributors to dental caries. They have a symbiotic relationship, allowing them to create an enhanced biofilm. Our goal was to examine whether two natural polyphenols (Padma hepaten (PH) and a polyphenol extraction from green tea (PPFGT)) could inhibit the caries-inducing properties of S. mutans and C. albicans. Methods: Co-species biofilms of S. mutans and C. albicans were grown in the presence of PH and PPFGT. Biofilm formation was tested spectrophotometrically. Exopolysaccharides (EPS) secretion was quantified using confocal scanning laser microscopy. Biofilm development was also tested on orthodontic surfaces (Essix) to assess biofilm inhibition ability on such an orthodontic appliance. Results: PPFGT and PH dose-dependently inhibited biofilm formation without affecting the planktonic growth. We found a significant reduction in biofilm total biomass using 0.625 mg/mL PPFGT and 0.16 mg/mL PH. A concentration of 0.31 mg/mL PPFGT and 0.16 mg/mL PH inhibited the total cell growth by 54% and EPS secretion by 81%. A reduction in biofilm formation and EPS secretion was also observed on orthodontic PVC surfaces. Conclusions: The polyphenolic extractions PPFGT and PH have an inhibitory effect on S. mutans and C. albicans biofilm formation and EPS secretion.

Freshwater turtles are being exploited for meat, eggs, traditional medicine, and pet trade. As a response, turtle farming became a booming aquaculture industry in the past two decades, specifically in the southeastern states of the United States of America (US) and across Southeast Asia. However, US turtle farms are currently producing turtles only for the pet trade while commercial trappers remain focused on catching the largest individuals from the wild. In our analyses we have created a biological and economic model that describes farming operations on a representative turtle farm in Louisiana. We first modeled current production of hatchling and yearling red-eared slider turtles (Trachemys scripta elegans) (i.e., traditional farming) for foreign and domestic pet markets, respectively. We tested the possibility of harvesting adult turtles from the breeding stock for sale to meat markets to enable alternative markets for the farmers, while decreasing the continued pressures on wild populations (i.e., non-traditional farming). Our economic model required current profit requirements of ~$13/turtle or ~$20.31/kg of meat from non-traditional farming in order to acquire the same profit as traditional farming, a value which currently exceeds market values of red-eared sliders. However, increasing competition with Asian turtle farms and decreasing hatchling prices may force the shift in the US toward producing turtles for meat markets. In addition, our model can be modified and applied to more desirable species on the meat market once more knowledge is acquired about species life histories and space requirements under farmed conditions.

Candida albicans is known as a commensal microorganism but it is also the most common fungal pathogen in humans, causing both mucosal and systemic infections. Biofilm-associated C. albicans infections present clinically important features due to their high levels of resistance to traditional antifungal agents. Quorum sensing is closely associated with biofilm formation and increasing fungal pathogenicity. We investigated the ability of the novel bacterial quorum sensing quencher thiazolidinedione-8 (S-8) to inhibit the formation of, and eradication of mature C. albicans biofilms. In addition, the capability of S-8 to alter fungal adhesion to mammalian cells was checked. S-8 exhibited specific antibiofilm and antiadhesion activities against C. albicans, at four- to eightfold lower concentrations than the minimum inhibitory concentration (MIC). Using fluorescence microscopy, we observed that S-8 dose-dependently reduces C. albicans-GFP binding to RAW macrophages. S-8 at sub-MICs also interfered with fungal morphogenesis by inhibiting the yeast-to-hyphal form transition. In addition, the tested agent strongly affected fungal cell wall characteristics by modulating its hydrophobicity. We evaluated the molecular mode of S-8 antibiofilm and antiadhesion activities using real-time RT-PCR. The expression levels of genes associated with biofilm formation, adhesion and filamentation, HWP1, ALS3 and EAP1, respectively, were dose-dependently downregulated by S-8. Transcript levels of UME6, responsible for long-term hyphal maintenance, were also significantly decreased by the tested agent. Both signaling pathways of hyphal formation-cAMP-PKA and MAPK-were interrupted by S-8. Their upstream general regulator RAS1 was markedly suppressed by S-8. In addition, the expression levels of MAPK cascade components CST20, HST7 and CPH1 were downregulated by S-8. Finally, transcriptional repressors of filament formation, TUP1 and NRG1, were dramatically upregulated by our compound. Our results indicate that S-8 holds a novel antibiofilm therapeutic mean in the treatment and prevention of biofilm-associated C. albicans infections.

Background:A low serum thyrotropin (TSH) concentration is an excellent predictor of hyperthyroidism, either overt or subclinical. Whether statin use influences the ability of a low serum TSH measurement to detect hyperthyroidism has not been evaluated.Methods:In a cohort of 307 patients with low or undetectable serum TSH concentrations suggestive of hyperthyroidism, we determined whether concurrent statin use influenced the results of radioiodine uptakes and scans. Participants included 29 patients taking a statin medication and 278 who were not taking a statin. Radioiodine uptakes and scans were interpreted by board-certified nuclear medicine physicians.Results:Sixteen of the 29 patients who were taking a statin (55) had normal radioiodine uptakes and scans despite their low serum TSH. The remaining 13 low-TSH patients who were taking a statin (45) had abnormal uptakes and scans, most commonly showing diffuse thyroid hyperplasia with increased radioiodine uptake. In contrast, the vast majority of the 278 patients not taking a statin had abnormal uptakes and scans (84), while only 16 of them had normal uptakes and scans (p< 0.001 vs. those on statins). The age- and sex-adjusted odds ratio of a statin user with a low serum TSH having normal radioiodine studies (as opposed to abnormal studies) was 3.6 (95 CI, 1.6–8.4).Conclusion:In patients with a low serum TSH concentration, normal thyroid function and morphology, as assessed by radioiodine studies, were much more common if the patient was taking a statin. Statins may falsely lower the serum TSH without altering thyroid function (“pseudohyperthyroidism”) or, alternatively, statins may improve thyroid function in patients with hyperthyroidism. [ABSTRACT FROM AUTHOR]