Breast Gangrene

<p>Abstract</p> <p>Background</p> <p>Breast gangrene is rare in surgical practice. Gangrene of breast can be idiopathic or secondary to some causative factor. Antibiotics and debridement are used for management. Acute inflammatory infiltrate, severe necrosis of breast tissue, necrotizing arteritis, and venous thrombosis is observed on histopathology. The aim of was to study patients who had breast gangrene.</p> <p>Methods</p> <p>A prospective study of 10 patients who had breast gangrene over a period of 6 years were analyzed</p> <p>Results</p> <p>All the patients in the study group were female. Total of 10 patients were encountered who had breast gangrene. Six patients presented with breast gangrene on the right breast whereas four had on left breast. Out of 10 patients, three had breast abscess after teeth bite followed by gangrene, one had iatrogenic trauma by needle aspiration of erythematous area of breast under septic conditions. Four had history of application of belladonna on cutaneous breast abscess and had then gangrene. All were lactating female. Amongst the rest two were elderly, one of which was a diabetic who had gangrene of breast and had no application of belladonna. All except one had debridement under cover of broad spectrum antibiotics. Three patients had grafting to cover the raw area.</p> <p>Conclusion</p> <p>Breast gangrene occurs rarely. Etiology is variable and mutifactorial. Teeth bite while lactation and the iatrogenic trauma by needle aspiration of breast abscess under unsterlised conditions could be causative. Uncontrolled diabetes can be one more causative factor for the breast gangrene. Belladonna application as a topical agent could be inciting factor. Sometimes gangrene of breast can be idiopathic. Treatment is antibiotics and debridement.</p

Differential contributory roles of nucleotide excision and homologous recombination repair for enhancing cisplatin sensitivity in human ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>While platinum-based chemotherapeutic agents are widely used to treat various solid tumors, the acquired platinum resistance is a major impediment in their successful treatment. Since enhanced DNA repair capacity is a major factor in conferring cisplatin resistance, targeting of DNA repair pathways is an effective stratagem for overcoming cisplatin resistance. This study was designed to delineate the role of nucleotide excision repair (NER), the principal mechanism for the removal of cisplatin-induced DNA intrastrand crosslinks, in cisplatin resistance and reveal the impact of DNA repair interference on cisplatin sensitivity in human ovarian cancer cells.</p> <p>Results</p> <p>We assessed the inherent NER efficiency of multiple matched pairs of cisplatin-sensitive and -resistant ovarian cancer cell lines and their expression of NER-related factors at mRNA and protein levels. Our results showed that only the cisplatin-resistant ovarian cancer cell line PEO4 possessed an increased NER capacity compared to its inherently NER-inefficient parental line PEO1. Several other cisplatin-resistant cell lines, including CP70, CDDP and 2008C13, exhibited a normal and parental cell-comparable NER capacity for removing cisplatin-induced DNA intrastrand cross-links (Pt-GG). Concomitant gene expression analysis revealed discordance in mRNA and protein levels of NER factors in various ovarian cancer cell lines and NER proteins level were unrelated to the cisplatin sensitivity of these cell lines. Although knockdown of NER factors was able to compromise the NER efficiency, it only caused a minimal effect on cisplatin sensitivity. On the contrary, downregulation of BRCA2, a critical protein for homologous recombination repair (HRR), significantly enhanced the efficacy of cisplatin in killing ovarian cancer cell line PEO4.</p> <p>Conclusion</p> <p>Our studies indicate that the level of NER factors in ovarian cancer cell lines is neither a determinant of their NER capacity nor of the sensitivity to cisplatin, and suggest that manipulation of the HRR but not the NER factor expression provides an effective strategy for sensitizing cisplatin-resistant tumors to platinating agents.</p

Bacteriological profile of wound infections and antimicrobial resistance in selected gram-negative bacteria

Background: Managing wound infections is a challenging task. Understanding their resistance pattern is an essential step at reducing its burden in hospital settings. Objective: To determine the bacteriological diversity of wound infections and the antimicrobial resistance exhibited by a selected Gram-negative bacterium in the Aljouf region of Saudi Arabia. Methods: The study retrospectively analysed the antibiograms of wound infections from hospitalized patients for the year 2019. The European Centre for Disease Control guidelines were adopted for the classification of resistant bacteria. Multidrug-, extensive drug-, and carbapenem-resistant isolates are presented as frequencies and percentages. Results: A total of 295 non-duplicate wound swab antibiograms were retrieved, 64.4% (190) and 35.6% (105) isolates were Gram-negative and Gram-positive bacterial infections respectively. Predominant pathogens included Staphylococcus species 21.0% (62), E. coli 16.3% (48) and K. pneumoniae 13.5% (40). 148 (77.9%), 42 (22.1%) and 43 (22.6%) of the Gram-negative isolates were multidrug-, extensively drug- and carbapenem-resistant. The antibiotic resistance exhibited by gram-negative bacteria was 43.4% (234/539), 59.1% (224/379) and 53.7% (101/188) towards carbapenems, 3rd - and 4th – generation cephalosporins. Conclusions: The majority of wound infections are caused by multidrug-, extensively drug- and carbapenem-resistant Gram-negative bacteria. Further studies should focus on the molecular basis of this resistance. Keywords: Wound infections; hospital; Gram-negative bacteria; antibiograms; multidrug-resistance; E. coli

Adherence of Primary Health Care Physicians to Hypertension Management Guidelines in Aljouf Region of Saudi Arabia

Abstract Introduction: Hypertension affects more than one-third of the world population and is a common public health problem. Primary health care physician&apos;s (PHCP&apos;s) adherence to the hypertension management guidelines constitutes an essential step for controlling hypertension

ASF1A and ATM regulate H3K56-mediated cell-cycle checkpoint recovery in response to UV irradiation

Successful DNA repair within chromatin requires coordinated interplay of histone modifications, chaperones and remodelers for allowing access of repair and checkpoint machineries to damaged sites. Upon completion of repair, ordered restoration of chromatin structure and key epigenetic marks herald the cell’s normal function. Here, we demonstrate such a restoration role of H3K56 acetylation (H3K56Ac) mark in response to ultraviolet (UV) irradiation of human cells. A fast initial deacetylation of H3K56 is followed by full renewal of an acetylated state at ~24–48 h post-irradiation. Histone chaperone, anti-silencing function-1 A (ASF1A), is crucial for post-repair H3K56Ac restoration, which in turn, is needed for the dephosphorylation of γ-H2AX and cellular recovery from checkpoint arrest. On the other hand, completion of DNA damage repair is not dependent on ASF1A or H3K56Ac. H3K56Ac restoration is regulated by ataxia telangiectasia mutated (ATM) checkpoint kinase. These cross-talking molecular cellular events reveal the important pathway components influencing the regulatory function of H3K56Ac in the recovery from UV-induced checkpoint arrest

Stable relocation of the radial head without annular ligament reconstruction using the Ilizarov technique to treat neglected Monteggia fracture: two case reports

<p>Abstract</p> <p>Introduction</p> <p>A Monteggia facture dislocation is not an uncommon injury, and the diagnosis can often be missed. Long-term follow-up of untreated Monteggia fracture dislocations reveals development of premature arthritis, pain, instability, and loss of pronation and supination. Methods involving annular ligament reconstruction require post-operative immobilization and use of transcapitellar pinning for maintenance of reduction, and thus a delay in rehabilitation. The literature reports satisfactory results with methods that involve ulnar osteotomy and open reduction of the radial head without annular ligament reconstruction. We used the Ilizarov method in two cases with neglected Monteggia fracture dislocations to stably reduce the radial head without open reduction and annular ligament reconstruction.</p> <p>Case presentation</p> <p>We report two cases of neglected Monteggia fracture dislocation, in two Kashmiri boys aged four and six years. Using ulnar osteotomy with distraction osteogenesis, we were able to relocate the radial head gradually and maintain the reduction without a requirement for open reduction and annular ligament reconstruction.</p> <p>Conclusion</p> <p>Distraction lengthening and hyperangulation in different planes by use of the Ilizarov technique effectively reduces the radial head without open reduction and annular ligament reconstruction.</p

Dissociation of CAK from Core TFIIH Reveals a Functional Link between XP-G/CS and the TFIIH Disassembly State

Transcription factor II H (TFIIH) is comprised of core TFIIH and Cdk-activating kinase (CAK) complexes. Here, we investigated the molecular and cellular manifestation of the TFIIH compositional changes by XPG truncation mutations. We showed that both core TFIIH and CAK are rapidly recruited to damage sites in repair-proficient cells. Chromatin immunoprecipitation against TFIIH and CAK components revealed a physical engagement of CAK in nucleotide excision repair (NER). While XPD recruitment to DNA damage was normal, CAK was not recruited in severe XP-G and XP-G/CS cells, indicating that the associations of CAK and XPD to core TFIIH are differentially affected. A CAK inhibition approach showed that CAK activity is not required for assembling pre-incision machinery in vivo or for removing genomic photolesions. Instead, CAK is involved in Ser5-phosphorylation and UV-induced degradation of RNA polymerase II. The CAK inhibition impaired transcription from undamaged and UV-damaged reporter, and partially decreased transcription of p53-dependent genes. The overall results demonstrated that a) XP-G/CS mutations affect the disassembly state of TFIIH resulting in the dissociation of CAK, but not XPD from core TFIIH, and b) CAK activity is not essential for global genomic repair but involved in general transcription and damage-induced RNA polymerase II degradation

ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle.

Cell cycle checkpoint is mediated by ATR and ATM kinases, as a prompt early response to a variety of DNA insults, and culminates in a highly orchestrated signal transduction cascade. Previously, we defined the regulatory role of nucleotide excision repair (NER) factors, DDB2 and XPC, in checkpoint and ATR/ATM-dependent repair pathway via ATR and ATM phosphorylation and recruitment to ultraviolet radiation (UVR)-induced damage sites. Here, we have dissected the molecular mechanisms of DDB2- and XPC- mediated regulation of ATR and ATM recruitment and activation upon UVR exposures. We show that the ATR and ATM activation and accumulation to UVR-induced damage not only depends on DDB2 and XPC, but also on the NER protein XPA, suggesting that the assembly of an active NER complex is essential for ATR and ATM recruitment. ATR and ATM localization and H2AX phosphorylation at the lesion sites occur as early as ten minutes in asynchronous as well as G1 arrested cells, showing that repair and checkpoint-mediated by ATR and ATM starts early upon UV irradiation. Moreover, our results demonstrated that ATR and ATM recruitment and H2AX phosphorylation are dependent on NER proteins in G1 phase, but not in S phase. We reasoned that in G1 the UVR-induced ssDNA gaps or processed ssDNA, and the bound NER complex promote ATR and ATM recruitment. In S phase, when the UV lesions result in stalled replication forks with long single-stranded DNA, ATR and ATM recruitment to these sites is regulated by different sets of proteins. Taken together, these results provide evidence that UVR-induced ATR and ATM recruitment and activation differ in G1 and S phases due to the existence of distinct types of DNA lesions, which promote assembly of different proteins involved in the process of DNA repair and checkpoint activation