Gender trends in dentistry: Dental faculty and academic leadership.

OBJECTIVES: Gender equality in the healthcare workforce has been a topic of discourse for many decades. In dental academia, women's representation of enrolled students and faculty has risen consistently since the 1980s. However, women in faculty leadership positions may still be lagging when compared to men. The purpose of this study was to evaluate the number of women who occupy the upper echelons of academic rank and title by analyzing cross-referenced data from the American Dental Association and the American Dental Education Association on women dental school graduates in relation to academic appointments. METHODS: Gender distribution in rank, title, and appointments in the decade from 2011 to 2019, as well as percentage of women graduates over the same period, were collected for descriptive statistics. Multiple linear regression analysis, Cochran Armitage, and chi-square tests were conducted to examine trends over the years and to determine significant differences in overall percentages (p < 0.05). RESULTS: The total women faculty percentages ranged from 36% to 40%. While the lower-level rank of instructor retained a higher representation of women (56%-65%), the higher rank of professor had disproportionately lower women percentages (18%-26%). Graduates, full-time faculty, lower-level academic ranks, and higher-level academic ranks for women followed similar upward trends that were statistically significant (p < 0.05). When comparing the different groups against each other, the annual increase in women DMD/DDS graduate percentage was higher than women full-time faculty (0.28%), instructor rank (0.92%), professor rank (0.50%), and department chair appointments (0.49%). CONCLUSIONS: Our data show that women are still underrepresented at higher academic ranks. However, the upward trends for professors, assistant deans, and program chairs suggest that in recent years, more women faculty may have been encouraged, mentored, or offered higher administrative positions in academic institutions.

Delayed diagnosis and subsequently increased severity of acute appendicitis (compatible with clinical-pathologic grounds) during the COVID-19 pandemic: an observational case-control study.

BACKGROUND: During a global crisis like the current COVID-19 pandemic, delayed admission to hospital in cases of emergent medical illness may lead to serious adverse consequences. We aimed to determine whether such delayed admission affected the severity of an inflammatory process regarding acute appendicitis, and its convalescence. METHODS: In a retrospective observational cohort case-control study, we analyzed the medical data of 60 patients who were emergently and consecutively admitted to our hospital due to acute appendicitis as established by clinical presentation and imaging modalities, during the period of the COVID-19 pandemic (our study group). We matched a statistically control group consisting of 97 patients who were admitted during a previous 12-month period for the same etiology. All underwent laparoscopic appendectomy. The main study parameters included intraoperative findings (validated by histopathology), duration of abdominal pain prior to admission, hospital stay and postoperative convalescence (reflecting the consequences of delay in diagnosis and surgery). RESULTS: The mean duration of abdominal pain until surgery was significantly longer in the study group. The rate of advanced appendicitis (suppurative and gangrenous appendicitis as well as peri-appendicular abscess) was greater in the study than in the control group (38.3 vs. 21.6%, 23.3 vs. 16.5%, and 5 vs. 1% respectively), as well as mean hospital stay. CONCLUSIONS: A global crisis like the current viral pandemic may significantly affect emergent admissions to hospital (as in case of acute appendicitis), leading to delayed surgical interventions and its consequences.

Microsurgery for management of primary and secondary lymphedema.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of lymphaticovenular anastomosis (LVA) in patients with lymphedema. METHODS: A retrospective analysis was conducted of 70 patients suffering from primary or secondary lymphedema who underwent LVA surgery with indocyanine green fluorescence lymphangiography. Postoperative evaluation included qualitative and quantitative volumetric assessment and analysis. Limb volume was measured by circumferential tape measurement volumetric method, in which the limb is subdivided into five segments and each segment's circumference is measured. RESULTS: LVA was performed in 70 patients, 22 with primary lymphedema and 48 with secondary lymphedema. The difference in preoperative upper limb volume was 35% with mean postoperative follow-up of 9 months. The mean number of lymphovenous bypasses was 3.9. The reduction in limb volume at 3, 6, and 12 months was 40.4%, 41%, and 45%, respectively. Patients with early-stage lymphedema had significantly higher volume reductions than patients with late-stage lymphedema at 3, 6, and 12 months (48% vs 18%, 49% vs 22%, and 65% vs 31%; P < .001). For lower extremity lymphedema, the preoperative volume differential was 25.5%. The mean postoperative follow-up was 9 months. The reduction in limb volume at 3, 6, and 12 months was 28%, 37%, and 39%, respectively. CONCLUSIONS: LVA surgery is a safe and effective method of reducing lymphedema severity, especially in upper extremity lymphedema at an earlier disease stage.

Resection of an axillary macrocystic lymphatic malformation in a 14-year-old girl using intraoperative indocyanine green lymphography.

Lymphangioma is a malformation of the lymphatic system for which surgical excision is a possible treatment. However, complete excision may be hindered by the lesion's size, anatomic location, unclear borders, and invasion into adjacent tissues. We describe a 14-year-old girl who presented with a rapidly progressing axillary swelling. Magnetic resonance imaging and ultrasound revealed a lymphatic macrocystic multilocular lesion. After preoperative and intraoperative indocyanine green lymphography, a complete surgical excision was achieved without damage to collateral lymphatic channels or surrounding tissues. Intraoperative indocyanine green lymphography may be useful in achieving efficient and safe resection of lymphangioma without damaging unconnected lymphatics.

A Case of Hemophagocytic Lymphohistiocytosis Associated With Mediterranean Spotted Fever in a Healthy 29-Year-Old Female.

A 29-year-old female presented with fever, headache, and epigastric pain. Though her initial presentation was benign and nonspecific, she soon developed a full-blown cytokine storm with disseminated intravascular coagulation. She was diagnosed with hemophagocytosis secondary to Rickettsia conorii infection. A good outcome was achieved thanks to prompt diagnosis and proper treatment.

Chylous ascites as a late complication of one anastomosis gastric bypass-minigastric bypass: case report.

BACKGROUND: One anastomosis gastric bypass- minigastric bypass (OAGB-MGB) is an emerging bariatric surgery that is being endorsed by surgeons worldwide. Internal herniation is a rare and dreaded complication after malabsorptive bariatric procedures, which necessitates early diagnosis and intervention. CASE PRESENTATION: We describe a 29-year-old male with chylous ascites caused by an internal hernia 8 months following laparoscopic one anastomosis gastric bypass. An abdominal CT showed enlargement of lymph nodes at the mesentery, with a moderate amount of liquid in the abdomen and pelvis. An emergent exploratory laparoscopic surgery demonstrated an internal hernia at the Petersen's space with a moderate quantity of chylous ascites. The patient made an uneventful recovery after surgery. CONCLUSIONS: Internal herniation can occur after OAGB-MGB and in extremely rare cases lead to chylous ascites. To our knowledge, this is the first reported case of chylous ascites following one anastomosis gastric bypass.

Correction: Chronic use of psychotropic medications in breastfeeding women: Is it safe?

[This corrects the article DOI: 10.1371/journal.pone.0197196.].

Chronic use of psychotropic medications in breastfeeding women: Is it safe?

BACKGROUND: Current knowledge regarding chronic use of psychotropic medications during breastfeeding is limited. The objective of this study was to evaluate the long-term effects of psychotropic monotherapy use during lactation on the breastfed infant. MATERIALS AND METHODS: In this prospective study, we followed 280 infants whose mothers contacted the Drug Consultation Center (DCC) at Assaf Harofeh Medical Center between January 2011 and December 2015, seeking information regarding the chronic use of psychotropic medications during lactation. This group was compared with a group of 152 callers, who inquired evidence regarding the use of antibiotics compatible with breastfeeding. Information on adverse effects, physical measures and gross motor developmental milestone achievements of the breastfed infants was obtained during a follow-up telephone interview. At follow up, the median age of the infants in the Psychotropic-drug group was 20 (11-33) months versus 36 (20-48) months in the Antibiotic group (p < 0.001). The outcomes were compared between the groups followed by a propensity score matching to control for difference in baseline characteristics. RESULTS: At follow-up, no significant differences between infants in the two groups were observed with regard to height, weight, head circumference and weight-length ratio percentile (p = 0.339, p = 0.223, p = 0.738, p = 0.926, respectively). Children in both groups were, according to their parents, within the normal developmental range for all milestones, according to the Denver Developmental Scale. Use of psychotropic medications during breastfeeding was not significantly associated with adverse reactions. After propensity score matching (n = 120 pairs) to control for differences in baseline characteristics and the length of lactation, only one significant difference was reported, sleepiness in infants in the study group (7/120) and none in the comparison group (p = 0.008). CONCLUSIONS: Chronic use of psychotropic monotherapy during lactation is associated with normal growth and gross motor developmental as by milestone achievements reported by parents. Sleepiness was reported, it seemed self-limited with no developmental effect.

Fatal and Near-Fatal Non-allergic Reactions in Patients with Underlying Cardiac Disease Receiving Benzathine Penicillin G in Israel and Switzerland.

Benzathine Penicillin G (BPG) is commonly used for treatment of penicillin-susceptible infections and secondary prevention of rheumatic fever. Death following administration of BPG is extremely rare-only a handful of cases have been described in the literature since the 1950's. In this case series from Israel and Switzerland, we describe nine cases of serious adverse reactions-six fatal reactions and three near-fatalities-occurring within minutes of receiving intramuscular BPG. Allergic reactions or faulty administration were not implicated in any of the cases; however, all patients had cardiac risk factors. This case series describes a relatively rare risk that should be borne in mind when prescribing BPG.

Safety of Mebendazole Use During Lactation: A Case Series Report.

INTRODUCTION: Mebendazole is an effective drug widely used in the treatment of parasitic infections. Although theoretically considered as safe during lactation, no studies have evaluated its potential adverse effects in infants of breastfeeding mothers. OBJECTIVES: We aimed to evaluate the safety of mebendazole in infants of lactating women treated with the drug. METHODS: Women referred for consultation regarding mebendazole use were invited to participate in the study. Overall 45 lactating women treated with various protocols of mebendazole were recruited in this case series study. RESULTS: Regardless of the treatment protocol used (single or repeated doses) mebendazole was well tolerated and was not associated with any adverse effects in infants of lactating mothers. There was mild GI irritability in two treated women. CONCLUSION: This study provides first evidence in humans as to the safety of mebendazole in breastfeeding.

Quality of life assessment in patients after mandibular resection and free fibula flap reconstruction.

PURPOSE: The aim of the present study was to assess patients' quality of life (QOL) after mandibular resection and reconstruction with the free fibula flap (FFF). MATERIALS AND METHODS: We performed a retrospective study of all patients who underwent segmental mandibular resection and FFF reconstruction at the Division of Oral and Maxillofacial Surgery, McGill University Health Center. The patients were contacted and asked to complete a QOL assessment at least 1 year after surgery. The patients' photographs were taken and evaluated for the esthetic outcomes after surgery by 2 dental health professionals using a visual analog scale and compared with the patients' self-evaluations. A descriptive analysis was used for data analysis. RESULTS: Seventeen patients underwent segmental mandibular resection and reconstruction with a FFF, and 11 completed the QOL questionnaire. Two patients were deceased at the start of the study, 1 refused to complete the QOL questionnaire, and 3 had developed disease recurrence and were not asked to complete the QOL questionnaire. Of the 11 patients who completed the QOL assessment, 8 rated their overall QOL as outstanding, very good, or good and 3 reported it to be fair. No significant correlation was found between the patients' self-reported esthetic evaluation and the third-party evaluations. CONCLUSIONS: Most patients who underwent mandibular resection and FFF reconstruction reported satisfaction with their overall QOL. We did not find a correlation between the patients' perceived esthetic outcome and the dental healthcare professionals' assessment.

Oral delivery system prolongs blood circulation of docetaxel nanocapsules via lymphatic absorption.

An original oral formulation of docetaxel nanocapsules (NCs) embedded in microparticles elicited in rats a higher bioavailability compared with the i.v. administration of the commercial docetaxel solution, Taxotere. In the present study, various animal studies were designed to elucidate the absorption process of docetaxel from such a delivery system. Again, the docetaxel NC formulation elicited a marked enhanced absorption compared with oral Taxotere in minipigs, resulting in relative bioavailability and Cmax values 10- and 8.4-fold higher, respectively, confirming the previous rat study results. It was revealed that orally absorbed NCs altered the elimination and distribution of docetaxel, as shown in the organ biodistribution rat study, due to their reinforced coating, while transiting through the enterocytes by surface adsorption of apoproteins and phospholipids. These findings were demonstrated by the cryogenic-temperature transmission electron microscopy results and confirmed by the use of a chylomicron flow blocker, cycloheximide, that prevented the oral absorption of docetaxel from the NC formulation in an independent pharmacokinetic study. The lipoproteinated NCs reduced the docetaxel release in plasma and its distribution among the organs. The improved anticancer activity compared with i.v. Taxotere, observed in the metastatic lung cancer model in Severe Combined Immune Deficiency-beige (SCID-bg) mice, should be attributed to the extravasation effect, leading to the lipoproteinated NC accumulation in lung tumors, where they exert a significant therapeutic action. To the best of our knowledge, no study has reported that the absorption of NCs was mediated by a lymphatic process and reinforced during their transit.

Antibody conjugated PLGA nanoparticles for targeted delivery of paclitaxel palmitate: efficacy and biofate in a lung cancer mouse model.

Aberrant signaling of the epidermal growth factor receptor (EGFR) is common to a variety of human cancers and is also found to be over-expressed in most cases of non-small cell lung cancer. For the development of a molecularly targeted therapy, cetuximab-conjugated nanoparticles (immunonanoparticles, INPs) are designed and loaded with the lipophilic paclitaxel palmitate (pcpl) prodrug. Oleyl cysteineamide (OCA) is synthesized whereby its amphiphilic nature enables interfacial anchoring and thiol surface functionalization of PLGA NPs, facilitating bioconjugation to cetuximab by thioether bonds. It is demonstrated that the in vitro targeting efficiency and improved cellular internalization and cytotoxicity of this targeted delivery system in lung cancer cells over-expressing EGFR. A quantitative measure of the high binding affinity of INPs to EGFR is demonstrated using surface plasmon resonance. In vivo tolerability and enhanced efficacy of cetuximab pcpl INPs in a metastatic lung cancer model are reported. Its therapeutic efficacy in A549-luc-C8 lung tumors is shown using non-invasive bioluminescent imaging. Intravenous administration of cetuximab pcpl INPs to mice results in significantly higher inhibition of tumor growth and increased survival rates as compared to the non-targeted drug solution, drug-loaded nanoparticles or blank INPs. Pharmacokinetics and organ biodistribution of the prodrug and parent drug are evaluated by LC-MS/MS in lung tumor bearing mice. No enhanced total accumulation of nanoparticles or INPs is found at the tumor tissue. However, persistent pcpl levels with sustained conversion and release of paclitaxel are observed for the encapsulated prodrug possibly suggesting the formation of a drug reservoir. The overall results indicate the potential of this promising targeted platform for the improved treatment of lung cancer and other EGFR positive tumors.

Safety and proof-of-concept efficacy of inhaled drug loaded nano- and immunonanoparticles in a c-Raf transgenic lung cancer model.

Pulmonary delivery of drug-loaded nanoparticles is a novel approach for lung cancer treatment and the conjugation of nanoparticles to a targeting ligand further promotes specificity of the carrier cargo to cancer cells. Notably, the epithelial cell adhesion molecule (EpCAM, CD326) is over expressed in lung cancer. Here, we report the safety and proof-of-concept efficacy of drug-loaded nanoparticles and EpCAM immunonanoparticles in a c-Raf transgenic lung cancer model. PEG-PLA nanoparticles and immunonanoparticles were prepared whereby paclitaxel palmitate (Pcpl) was incorporated as a medication for its common use in lung cancer treatment. Four doses of aerosolized nanoparticle formulations or vehicle were endotracheally administered to mice by consecutive or alternate regimes. Pulmonary delivery of drug loaded nano- and/or immunonanoparticle formulations elicited mild inflammation as evidenced by the slightly increased neutrophil and activated macrophage counts in bronchoalveolar lavage. No evidence for pulmonary toxicity following treatment with either blank or drug-loaded nano- and/or immunonanoparticles was observed. Proof-of-concept efficacy was determined by serial CT scanning and histopathology. Animals treated with either EpCAM antibody or Pcpl solution or drug loaded nano- or immunonanoparticles inhibited disease progression. Conversely, disease progression was noted with vehicle treated animals with nearly 30% loss of their aerated lung volume. Importantly, treatment of mice with either Pcpl or EpCAM antibody solution caused 80% mortality and/or haemorrhage, respectively, thus causing unacceptable toxicity. In contrast, the survival of animals treated with either nano- or immunonanoparticles was 60 and 70%, respectively. Taken collectively, pulmonary delivered drug-loaded nano- and EpCAM immunonanoparticles were well tolerated and can be considered a promising strategy for improving lung cancer treatment.

The ligand nanoparticle conjugation approach for targeted cancer therapy.

Cancer therapy often requires frequent and high drug dosing. Yet, despite the significant progress in cancer research and the wide versatility of potent available drugs, treatment efficacy is still hurdled and often failed by the lack of pharmaco-selectivity to diseased cells, indiscriminate drug toxicities and poor patient compliance. Thus, innovative pharmaceutical solutions are needed to effectively deliver the cytotoxic drugs specifically to the tumor site while minimizing systemic exposure to frequent and high drug doses. Polymeric nanocarriers, particularly nanoparticles, have been extensively studied for improved oncological use. Such nanocarriers hold great potential in cancer treatment as they can be biocompatible, adapted to specific needs, tolerated and deliver high drug payloads while targeting tumors. Active targeting, as opposed to passive targeting, should add value to selective and site specific treatment. Active targeting of nanosized drug delivery systems is firmly rooted in the Magic Bullet Concept as was envisioned by Paul Ehrlich over 100 years ago. This targeting strategy is based on the molecular recognition of tumor biomarkers which are over-expressed on cancer cells, via specific vector molecules conjugated to the surface of the drug carrier. These vector molecules dictate the carrier's biodistribution and its biological affinity to the desired site of action. Many recent publications have shown encouraging results suggesting that targeting nanocarriers represent a highly-promising strategy for improved cancer treatment. This chapter will focus mainly on polymeric nanoparticles as the main drug carriers to be conjugated to various ligands able to deliver the drug to the specific desired pathological tissue.