Hypothyroidism conversion to hyperthyroidism: it's never too late.

Primary hypothyroidism is a common endocrine condition, most commonly caused by autoimmune thyroiditis (Hashimoto's disease) while Graves' disease is the most common cause of hyperthyroidism. Hypothyroidism is usually a permanent condition in most patients requiring lifelong levothyroxine treatment. Transformation from Hashimoto's disease to Graves' disease is considered rare but recently been increasingly recognised. We describe a case of a 61-year-old lady who was diagnosed with hypothyroidism approximately three decades ago and treated with levothyroxine replacement therapy. Approximately 27 years after the initial diagnosis of hypothyroidism, she started to become biochemically and clinically hyperthyroid. This was initially managed with gradual reduction in the dose of levothyroxine, followed by complete cessation of the medication, but she remained hyperthyroid, ultimately requiring anti-thyroid treatment with Carbimazole. This case highlights that there should be a high index of suspicion for a possible conversion of hypothyroidism to hyperthyroidism, even many years after the initial diagnosis of hypothyroidism. To our knowledge, this case illustrates the longest reported time interval between the diagnosis of hypothyroidism until the conversion to hyperthyroidism. Learning points: Occurrence of Graves' disease after primary hypothyroidism is uncommon but possible.In this case, there was a time-lapse of almost 28 years and therefore this entity may not be as rare as previously thought.Diagnosis requires careful clinical and biochemical assessment. Otherwise, the case can be easily confused for over-replacement of levothyroxine.We suggest measuring both anti-thyroid peroxidase (TPO) antibodies and TSH receptor antibodies (TRAB) in suspected cases.The underlying aetiology for the conversion is not exactly known but probably involves autoimmune switch by an external stimulus in genetically susceptible individuals

Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?

Background: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. Method: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). Results: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. Conclusion: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies

Fungal volatile organic compounds: emphasis on their plant growth-promoting

Fungal volatile organic compounds (VOCs) commonly formed bioactive interface between plants and countless of microorganisms on the above- and below-ground plant-fungus interactions. Fungal-plant interactions symbolize intriguingly biochemical complex and challenging scenarios that are discovered by metabolomic approaches. Remarkably secondary metabolites (SMs) played a significant role in the virulence and existence with plant-fungal pathogen interaction; only 25% of the fungal gene clusters have been functionally identified, even though these numbers are too low as compared with plant secondary metabolites. The current insights on fungal VOCs are conducted under lab environments and to apply small numbers of microbes; its molecules have significant effects on growth, development, and defense system of plants. Many fungal VOCs supported dynamic processes, leading to countless interactions between plants, antagonists, and mutualistic symbionts. The fundamental role of fungal VOCs at field level is required for better understanding, so more studies will offer further constructive scientific evidences that can show the cost-effectiveness of ecofriendly and ecologically produced fungal VOCs for crop welfare

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Challenges and Considerations in Assessing GERD: A Critical Review of a Study in Southern Punjab, Pakistan [Response to Letter]

Muhammad Fawad Rasool,1 Rimsha Sarwar,1 Muhammad Subhan Arshad,1,2 Imran Imran,3 Hamid Saeed,4 Abdul Majeed,1 Muqarrab Akbar,5 Muhammad Omer Chaudhry,6 Anees Ur Rehman,1 Waseem Ashraf,3 Tanveer Ahmad,7 Waleed Badoghaish,8 Faleh Alqahtani9 1Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, Pakistan; 2Department of Pharmacy, Southern Punjab Institute of Health Sciences, Multan, 60000, Pakistan; 3Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, Pakistan; 4University College of Pharmacy, Allama Iqbal Campus, University of the Punjab, Lahore, 54000, Pakistan; 5Department of Political Science, Bahauddin Zakariya University, Multan, 60800, Pakistan; 6School of Economics, Bahauddin Zakariya University, Multan, 60800, Pakistan; 7Institute for Advanced Biosciences (Iab), CNRS UMR5309, INSERM U1209, Grenoble Alpes University, La Tronche, 38700, France; 8Department of Internal Medicine, College of Medicine, University of Tabuk, Tabuk, 71411, Saudi Arabia; 9Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi ArabiaCorrespondence: Muhammad Fawad Rasool; Faleh Alqahtani, Email [email protected]; [email protected]

Uncoordinated Loss of Chromatid Cohesion Is a Common Outcome of Extended Metaphase Arrest

Chromosome segregation requires coordinated separation of sister chromatids following biorientation of all chromosomes on the mitotic spindle. Chromatid separation at the metaphase-to-anaphase transition is accomplished by cleavage of the cohesin complex that holds chromatids together. Here we show using live-cell imaging that extending the metaphase bioriented state using five independent perturbations (expression of non-degradable Cyclin B, expression of a Spindly point mutant that prevents spindle checkpoint silencing, depletion of the anaphase inducer Cdc20, treatment with a proteasome inhibitor, or treatment with an inhibitor of the mitotic kinesin CENP-E) leads to eventual scattering of chromosomes on the spindle. This scattering phenotype is characterized by uncoordinated loss of cohesion between some, but not all sister chromatids and subsequent spindle defects that include centriole separation. Cells with scattered chromosomes persist long-term in a mitotic state and eventually die or exit. Partial cohesion loss-associated scattering is observed in both transformed cells and in karyotypically normal human cells, albeit at lower penetrance. Suppressing microtubule dynamics reduces scattering, suggesting that cohesion at centromeres is unable to resist dynamic microtubule-dependent pulling forces on the kinetochores. Consistent with this view, strengthening cohesion by inhibiting the two pathways responsible for its removal significantly inhibits scattering. These results establish that chromosome scattering due to uncoordinated partial loss of chromatid cohesion is a common outcome following extended arrest with bioriented chromosomes in human cells. These findings have important implications for analysis of mitotic phenotypes in human cells and for development of anti-mitotic chemotherapeutic approaches in the treatment of cancer

Childhood asthma and indoor allergens in Native Americans in New York

BACKGROUND: The objective of this study was to assess the correlation between childhood asthma and potential risk factors, especially exposure to indoor allergens, in a Native American population. METHODS: A case-control study of St. Regis Mohawk tribe children ages 2–14 years, 25 diagnosed with asthma and 25 controls was conducted. Exposure was assessed based on a personal interview and measurement of mite and cat allergens (Der p 1, Fel d 1) in indoor dust. RESULTS: A non-significant increased risk of childhood asthma was associated with self-reported family history of asthma, childhood environmental tobacco smoke exposure, and air pollution. There was a significant protective effect of breastfeeding against current asthma in children less than 14 years (5.2 fold lower risk). About 80% of dust mite and 15% of cat allergen samples were above the threshold values for sensitization of 2 and 1 μg/g, respectively. The association between current asthma and exposure to dust mite and cat allergens was positive but not statistically significant. CONCLUSION: This research identified several potential indoor and outdoor risk factors for asthma in Mohawks homes, of which avoidance may reduce or delay the development of asthma in susceptible individuals