Structural biases in disordered proteins are prevalent in the cell.

Intrinsically disordered proteins and protein regions (IDPs) are prevalent in all proteomes and are essential to cellular function. Unlike folded proteins, IDPs exist in an ensemble of dissimilar conformations. Despite this structural plasticity, intramolecular interactions create sequence-specific structural biases that determine an IDP ensemble's three-dimensional shape. Such structural biases can be key to IDP function and are often measured in vitro, but whether those biases are preserved inside the cell is unclear. Here we show that structural biases in IDP ensembles found in vitro are recapitulated inside human-derived cells. We further reveal that structural biases can change in a sequence-dependent manner due to changes in the intracellular milieu, subcellular localization, and intramolecular interactions with tethered well-folded domains. We propose that the structural sensitivity of IDP ensembles can be leveraged for biological function, can be the underlying cause of IDP-driven pathology or can be used to design disorder-based biosensors and actuators.

Interhelical E@g-N@a interactions modulate coiled coil stability within a de novo set of orthogonal peptide heterodimers.

The designability of orthogonal coiled coil (CC) dimers, which draw on well-established design rules, plays a pivotal role in fueling the development of CCs as synthetically versatile assembly-directing motifs for the fabrication of bionanomaterials. Here, we aim to expand the synthetic CC toolkit through establishing a "minimalistic" set of orthogonal, de novo CC peptides that comprise 3.5 heptads in length and a single buried Asn to prescribe dimer formation. The designed sequences display excellent partner fidelity, confirmed via circular dichroism (CD) spectroscopy and Ni-NTA binding assays, and are corroborated in silico using molecular dynamics (MD) simulation. Detailed analysis of the MD conformational data highlights the importance of interhelical E@g-N@a interactions in coordinating an extensive 6-residue hydrogen bonding network that "locks" the interchain Asn-Asn' contact in place. The enhanced stability imparted to the Asn-Asn' bond elicits an increase in thermal stability of CCs up to ~15°C and accounts for significant differences in stability within the collection of similarly designed orthogonal CC pairs. The presented work underlines the utility of MD simulation as a tool for constructing de novo, orthogonal CCs, and presents an alternative handle for modulating the stability of orthogonal CCs via tuning the number of interhelical E@g-N@a contacts. Expansion of CC design rules is a key ingredient for guiding the design and assembly of more complex, intricate CC-based architectures for tackling a variety of challenges within the fields of nanomedicine and bionanotechnology.

Strengthening rural surgery in the Philippines: Essential in achieving universal health care.

The Lancet Commission on Global Surgery (LCoGS) launched Global Surgery 2030 to address the surgical services inequities with a bias toward low-income and middle-income countries like the Philippines. The same inequity is observed particularly when it comes to the urban-rural divide. With more than half of the population living in rural areas, access to surgery becomes a major challenge that further impedes the much-needed health of an economically productive workforce. The Universal Health Care [UHC] Act (RA 11332) of 2019 ensures that all Filipinos have access to quality, cost-effective, promotive, preventive, curative, rehabilitative, and palliative health services without causing a financial burden. Recognizing the provision of essential surgery, in the context of primary healthcare is important. It should be accessible, continuous, comprehensive, and coordinated at the time of need - parallel to the principle of primary health care. Driven by this concept and experiences, the authors conceptualized and presented the Philippine Rural Surgery model for future development and implementation. This is envisioned to provide essential surgery among local rural primary health care settings that is universal, accessible, cost-effective and safe. As this is still new in the Philippines, we proposed tenets and recommendations based on WHO Health System Strengthening building blocks to guide stakeholders in creating formal plans towards institutionalization under the principles of UHC. Such access to surgical service in the context of a unique socio-demography of the Philippines would be essential in attaining the parameters and provisions set by the UHC Act.

Long term outcome of a subcutaneous colonic interposition after pharyngo-laryngectomy for strictures of the larynx and hypopharynx resulting from caustic ingestion: A case report.

INTRODUCTION: Caustic agents, also called corrosive agents, could be acids or alkali in nature. If ingested, these agents can injure any part of the aerodigestive tree. Extent of injury depends on the type, concentration, duration of exposure and volume of caustic agent ingested. Serious complications after caustic agent ingestion can occur both in the short term such as hollow viscus perforation and death and in the long term such as stricture formation causing obstruction and lifetime risk of development of carcinoma. PRESENTATION OF A CASE: This is a case of a 25-year-old female who ingested an unknown substance resulting to a severe stricture of the larynx, hypopharynx, esophagus and pyloroantral region of the stomach. Six months after her tracheostomy and tube jejunostomy, she sought further medical attention in our institution due to inability to swallow food and saliva. She underwent pharyngolaryngectomy (PL) with the strictured esophagus and stomach left in-situ due to extensive adhesions. The subcutaneous colonic interposition reestablished the alimentary continuity by providing enough length for tension-free anastomosis and a more direct route for cervical anastomosis. DISCUSSION: Stricture formation is one of the most challenging late complication of corrosive injury. It results from scar formation in response to inflammation of the aerodigestive tract. Key factors in managing caustic strictures include safety of strictured segment resection, choice of replacement organ for reconstruction and route of conduit. CONCLUSION: Timing of surgery and proper selection the surgical procedure for complications of caustic ingestion can result in excellent long term outcomes.

Disseminated Melioidosis presenting as pneumonia, femoral and sacral osteomyelitis, splenic abscess and high rectal fistula: A case report and review of literature.

INTRODUCTION: Melioidosis is a rare infectious tropical disease caused by Burkholderia pseudomallei (B. pseudomallei), an environmental saprophyte usually habitating on soils of Southeast Asian fields. Most of the reported cases present with pneumonia and intra-abdominal abscess. Diagnosis is established by culture studies from the blood, sputum or abscess drainage. Management relies on culture-guided antibiotic treatment, with good prognosis. Surgical intervention is required in cases not responsive to medical management. PRESENTATION OF CASE: We are presenting a case of Melioidosis in a 72 year old Filipino who presented with Pneumonia, Femoral and Sacral Osteomyelitis, Splenic Abscess and High Rectal Fistula. He was successfully managed with systemic antibiotic treatment and surgery. The splenic abscess was managed by splenectomy and a transverse loop colostomy was used for fecal diversion to address the rectal fistula. DISCUSSION: Melioidosis varies in its presentation and thus management should be individualized, depending on the organs involved. Our patient presented with multiple foci of infection which rendered the treatment more complicated as compared to those reported previously in published literature. The pneumonia and the osteomyelitis were managed with aggressive systemic antibiotics but the other sites of infection required drainage and surgery. CONCLUSION: Melioidosis is a rare infection caused by an environmental saprophyte Burkholderia pseudomallei. An accurate diagnosis using culture studies is essential to institute appropriate treatment. Antibiotic treatment complemented by surgery for specific organ involvement is essential for cure.

Duodenal perforation secondary to stent migration after ERCP for hepatobiliary tuberculosis: Case report of a lethal complication in a young patient.

INTRODUCTION: Interventional internal drainage of the biliary tract has become an established procedure for the temporary and definitive treatment of biliary obstruction due to malignant or benign disease. The complication rate is reported to be so low that when feasible, this technique is preferred over a surgical drainage procedure. PRESENTATION OF A CASE: A 26-year old woman was referred to the hepatopancreaticobiliary surgery service due to severe abdominal pain for 3 days after undergoing endoscopic retrograde cholangiopancreatography (ERCP). She underwent biliary dilatation and stent insertion for obstructive jaundice secondary to biliary stricture from hepatobiliary tuberculosis. The patient underwent exploratory laparotomy, peritoneal lavage, duodenorrhaphy and tube jejunostomy for bilious peritonitis and duodenal perforation from biliary stent migration. The patient died one day post-operation due to septic shock from secondary bacterial peritonitis. DISCUSSION: ERCP and other interventional endoscopic biliary interventions are increasingly being used for biliary obstruction. Despite the various complications which arise from these diagnostic and therapeutic modalities, complications are relatively uncommon. Duodenal perforation from biliary stent migration is a rare complication after undergoing ERCP and stenting. However, in patients presenting with severe pain and physical signs of acute abdomen after the procedure, it should always be a consideration. CONCLUSIONS: Despite the relative safety of interventional techniques for biliary obstruction, complications like pancreatitis, hemorrhage and perforation may occur. Early recognition and high index of suspicion allows for early intervention with good outcomes. Duodenal perforation from stent migration can occur and when intervention is delayed may lead to morbidity and mortality.

Gallbladder duplication complicated by cholecystitis and unsuspected choledocholithiasis: A case report and review of literature.

INTRODUCTION: Gallbladder duplication is a rare congenital anomaly of the biliary tree. Although a double gallbladder by itself is not clinically significant, complications of gallstone disease increases the complexity of the management. Preoperative recognition decreases the risk of complications during laparoscopic cholecystectomy. PRESENTATION OF CASE: Presented herein is the case of a 52 year old who presented with abdominal pain. A transabdominal ultrasound was suggestive of a gallbladder duplication with the larger gallbladder filled with cholelithiasis. Subsequent imaging studies, including an endoluminal ultrasound, confirmed the diagnosis and documented a choledocholithiasis. Endoscopic extraction of the biliary stone with subsequent laparoscopic cholecystectomy of both gallbladders was successfully performed. DISCUSSION: This case is being presented not only for the rarity of the condition but also of the challenges in management it poses. In gallbladder duplication, pathologic involvement of one gallbladder requires removal of both gallbladders. A high index of suspicion on initial scanning warrants further delineation of the important anatomic structures of the biliary tree to avoid perioperative complications. CONCLUSION: Laparoscopic cholecystectomy may be safely performed in patients with gallbladder duplication. Preoperative recognition with appropriate imaging modalities, including ultrasound and MRCP may avoid surgical complications. In cases where the anomaly is detected intraoperatively during cholecystectomy, meticulous dissection and intraoperative cholangiography will avoid iatrogenic injuries and lead to successful outcomes.

Colouterine fistula: A case report of a rare complication of diverticular disease managed during the pandemic.

INTRODUCTION AND IMPORTANCE: Colouterine fistulas related to diverticulitis are very rare due to the thickness of the uterine myometrium. Other causes related to colouterine fistula formation particularly malignancy, have to be considered. Diagnosis by imaging or endoscopy may be inconclusive. CASE PRESENTATION: We are presenting a case of a 70-year-old female who presented with malodorous vaginal discharge and painful labial lesions. No previous history of surgery, gynecologic malignancy or other possible causes of the fistula was elicited. CT scan imaging suggested a colouterine fistula. The patient was admitted and underwent Exploratory laparotomy, Hartmann's procedure and total hysterectomy with bilateral salpingo oophorectomy. The patient was discharged without perioperative complications. CLINICAL DISCUSSION: Colouterine fistulas are extremely rare complications of diverticular disease. Diagnosis entails clinical astuteness and judicious use of imaging and endoscopic modalities. Accurate diagnosis is essential to select the appropriate surgical approach, along with intraoperative findings patient status and prevailing conditions. CONCLUSION: This case is being presented not only for the rarity of the case but also for the complexity of the management and decision making during the period of the pandemic.

Radical surgery for primary thyroid lymphoma in a Filipino female: Report of a case and review of literature.

INTRODUCTION: Primary thyroid lymphomas are rare. They constitute only 2% of all thyroid malignancies. It is important to distinguish it from other tumors of the thyroid due to the marked difference in approach to management. Preoperative diagnostic confirmation is ideal to allow for appropriate therapeutic management, which consists of chemotherapy with or without radiotherapy and to avoid unnecessary surgery. In a select group of patients, surgery may be of benefit to relieve obstructive symptoms and establish diagnosis. CASE PRESENTATION: Presented herein is a 48 year old female with a progressively enlarging neck mass previously being treated for Hashimoto's thyroiditis. Obstructive symptoms and a preoperative diagnosis of anaplastic carcinoma prompted surgical intervention. The patient underwent resection of the tumor with a total thyroidectomy and bilateral neck dissection. Post -operative diagnosis of non Hodgkins diffuse large B cell type of lymphoma was made. DISCUSSION: Primary thyroid lymphomas are rare tumors that may present similarly with some types of thyroid malignancies. An accurate diagnosis is important because non-surgical treatment options like combination chemotherapy and radiotherapy may be effective while sparing the patient from unnecessary radical surgery. CONCLUSION: Primary thyroid lymphoma must be a differential diagnosis in patients presenting with large thyroid tumors in the background of Hashimoto's thyroiditis. Although chemoradiotherapy is the preferred treatment approach, there is a role for surgery in cases of tumor obstruction and uncertain diagnosis.

A randomized, double-blind, placebo-controlled trial to determine effectiveness of antibiotic prophylaxis for tension-free mesh herniorrhaphy.

BACKGROUND: In recent years, use of prosthetic material for inguinal hernia repair has increased dramatically. Tension-free repairs have gained popularity not only for recurrent or complicated hernias, but for primary hernia repairs as well. Although routine use of prophylactic antibiotics is not recommended in the Philippines for open nonimplant herniorrhaphy, there is little direct clinical evidence on which to base recommendations when implantable mesh is used. STUDY DESIGN: We conducted a prospective, randomized, double-blind, placebo-controlled trial comparing wound infection rates in 360 patients (180 received prophylactic antibiotics, 180 received a placebo) undergoing primary inguinal hernia repair electively using polypropylene mesh. Age, gender, American Society of Anesthesiologists class, type of hernia, type of anesthesia, and duration of operation were recorded. Infections were evaluated 1 week, 2 weeks, and 1 month after operation by an independent surgeon. All complications were recorded. Results were assessed using chi-square, Fisher's exact test, and Student's t-tests as appropriate. RESULTS: Groups were well matched for all preoperative variables studied, including comorbid conditions. Six patients from the antibiotic group and four from the placebo group failed to followup after the second week. Superficial surgical site infection developed in 3 patients (1.7%) from the antibiotic group and 6 (3.3%) from the placebo group (p = 0.50). One from each group developed deep surgical site infection. Both patients were readmitted and underwent repeated debridement, which eventually resulted in graft loss. CONCLUSIONS: Preoperative administration of single-dose antibiotic for tension-free inguinal mesh herniorrhaphy did not markedly decrease risk of wound infection in this patient population. Our results do not support use of antibiotic prophylaxis for tension-free mesh herniorrhaphy.