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Protein kinases are a large class of enzymes with numerous biological roles and many have been implicated in a vast array of diseases, including cancer and the novel coronavirus infection COVID-19. Thus, the development of chemical probes to selectively target each kinase is of great interest. Inhibition of protein kinases with ATP-competitive inhibitors has historically been the most widely used method. However, due to the highly conserved structures of ATP-sites, the identification of truly selective chemical probes is challenging. In this review, we use the Ser/Thr kinase CK2 as an example to highlight the historical challenges in effective and selective chemical probe development, alongside recent advances in the field and alternative strategies aiming to overcome these problems. The methods utilised for CK2 can be applied to an array of protein kinases to aid in the discovery of chemical probes to further understand each kinase\'s biology, with wide-reaching implications for drug development.

Cardiobacterium hominis est un bacille à Gram négatif responsable d\'endocardites infectieuses, principalement chez les patients atteints de pathologies cardiaques ou porteurs de valves. L\'identification de cette bactérie est souvent complexe et peut être la cause d\'un diagnostic et d\'une prise en charge tardifs, source de complications cardiaques. Cet article présente la prise en charge d\'une endocardite infectieuse associée à un sepsis à Cardiobacterium hominis, les difficultés d\'identification de cette bactérie, ainsi qu\'une revue de la littérature sur les infections dues à cette bactérie.

Acellular human dermal allograft commonly is used in the surgical treatment of complex rotator cuff tears, but little information is known about the biological fate of these grafts in human subjects. In this case report, the authors describe a patient who presented with a radiographically healed acellular human dermal allograft superior capsular reconstruction but had humeral head avascular necrosis. The healed superior capsular reconstruction, including graft-bone interfaces, was explanted after 7 months and sent for histologic analysis. A successful biological reconstruction of the superior capsule was found. The graft demonstrated gross and microscopic incorporation with the host, including a tendon-like structure, aligned collagen fibers, fibroblast-like cells, and no clear graft-host distinction. Cellular infiltration ranged from 5% to 14% (central graft) to 65% to 92% (sutured attachment points). Neovascularization and active graft remodeling were confirmed histologically. LEVEL OF EVIDENCE: V, case report.

Recently, basidiomycete Schizophyllum commune has been reported as a cause of allergic bronchopulmonary mycosis. However, it is rare as a cause of otitis externa. We experienced a very rare case of otitis externa caused by S. commune in a 68-year-old man with a history of chronic otitis media. We performed Gram staining at the first consultation and follow-up treatment and found fungal cells on the smear and treated him with an appropriate antifungal drug. The results of identification and antifungal susceptibility testing obtained in cooperation with clinical microbiologists at other facilities was very important for future treatment planning decisions. Medical practitioners worldwide should introduce a Gram staining tool into their workflow and cooperate closely with clinical microbiologists to achieve antimicrobial stewardship.

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OBJECTIVE: Studies examining cervicitis aetiology and prevalence lack comparability due to varying criteria for cervicitis. We aimed to outline cervicitis associations and suggest a best case definition.
METHODS: A cross-sectional study of 558 women at three sexually transmitted infection clinics in Sydney, Australia, 2006-2010, examined pathogen and behavioural associations of cervicitis using three cervicitis definitions: \'microscopy\' (>30 pmnl/hpf (polymorphonuclear leucocytes per high-powered field on cervical Gram stain)), \'cervical discharge\' (yellow and/or mucopurulent cervical discharge) or \'micro+cervical discharge\' (combined \'microscopy\' and \'cervical discharge\').
RESULTS: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV) and Neisseria gonorrhoeae (NG) had the strongest associations with cervicitis definitions \'micro+cervical discharge\': CT adjusted prevalence ratio (APR)=2.13 (95% CI 1.38 to 3.30) p=0.0006, MG APR=2.21 (1.33 to 3.69) p=0.002, TV APR=2.37 (1.44 to 3.90) p=0.0007 NG PR=4.42 (3.79 to 5.15) p<0.0001 and \'cervical discharge\': CT APR=1.90 (1.25 to 2.89) p=0.003, MG APR=1.93 (1.17 to 3.19) p=0.011, TV APR=2.02 (1.24 to 3.31) p=0.005 NG PR=3.88 (3.36 to 4.48) p<0.0001. Condom use for vaginal sex \'always/sometimes\' reduced cervicitis risk: (\'micro+cervical discharge\') APR=0.69 (0.51 to 0.93) p=0.016. Combined population attributable risk % (PAR%) of these four pathogens was only 18.0% with a protective PAR% of condoms of 25.7%. Exposures not associated with cervicitis included bacterial vaginosis, Mycoplasma hominis, Ureaplasma urealyticum, herpes simplex virus 1&2, cytomegalovirus, Candida, age, smoking and hormonal contraception.
CONCLUSIONS: Cervicitis was associated with CT, MG, TV and NG with combined PAR% of these pathogens only 18% in this setting, suggesting other factors are involved. Condoms significantly reduced cervicitis risk. Cervicitis definitions with best clinical utility and pathogen prediction were \'cervical discharge\' and \'micro+cervical discharge\'.

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A 32-year-old man was admitted to our hospital because of fever, headache, and loss of consciousness. Four days before admission, he had had difficulty speaking. On the day of admission, his colleague had found him to be unconscious and lying on his back. He was admitted to our hospital. The temperature at the eardrum was 35.2°C. Neurologic evaluation was negative. Computed tomography (CT) scan of the brain showed slight ventricular enlargement bilaterally. An X-ray film of the chest showed no abnormality. On the second hospital day, neck stiffness was noted. The cerebrospinal fluid (CSF) contained 870 white cells/μl, most of which were neutrophils; the glucose level in the CSF was 10 mg/dl, and the protein level was 140 mg/dl. Stained smears of the CSF, including Gram staining and India-ink preparations, disclosed no microorganisms. Capsular antigen tests for several bacteria were negative. Antimicrobial agents were started. However, by changing the microscope focus slightly while viewing Gram stains of the CSF, we could see brightened and Gram-positive bacilli that had been phagocytosed by neutrophils. This finding suggested the presence of Mycobacterium tuberculosis. Ziehl-Neelsen staining of the CSF and gastric juice revealed anti-acid bacilli. Polymerase chain reaction for M. tuberculosis in the gastric juice was positive. This case showed that Gram staining could be useful as an initial adjunct for the diagnosis of tuberculous meningitis, particularly when the CSF shows predominantly neutrocytic pleocytosis, but no other evidence of bacterial meningitis.